Ignite Creation Date:
2025-12-24 @ 10:17 PM
Ignite Modification Date:
2025-12-31 @ 3:42 AM
Study NCT ID:
NCT01973335
Status:
COMPLETED
Last Update Posted:
2019-05-21
First Post:
2013-10-25
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Acetazolamide and Spironolactone to Increase Natriuresis in Congestive Heart Failure
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D006333', 'term': 'Heart Failure'}, {'id': 'D059347', 'term': 'Cardio-Renal Syndrome'}], 'ancestors': [{'id': 'D006331', 'term': 'Heart Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}, {'id': 'D051437', 'term': 'Renal Insufficiency'}, {'id': 'D007674', 'term': 'Kidney Diseases'}, {'id': 'D014570', 'term': 'Urologic Diseases'}, {'id': 'D052776', 'term': 'Female Urogenital Diseases'}, {'id': 'D005261', 'term': 'Female Urogenital Diseases and Pregnancy Complications'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D052801', 'term': 'Male Urogenital Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D003131', 'term': 'Combined Modality Therapy'}, {'id': 'D000086', 'term': 'Acetazolamide'}, {'id': 'D049994', 'term': 'Sodium Potassium Chloride Symporter Inhibitors'}, {'id': 'D002034', 'term': 'Bumetanide'}, {'id': 'D013148', 'term': 'Spironolactone'}], 'ancestors': [{'id': 'D013812', 'term': 'Therapeutics'}, {'id': 'D013830', 'term': 'Thiadiazoles'}, {'id': 'D013844', 'term': 'Thiazoles'}, {'id': 'D013457', 'term': 'Sulfur Compounds'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D001393', 'term': 'Azoles'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D049990', 'term': 'Membrane Transport Modulators'}, {'id': 'D045504', 'term': 'Molecular Mechanisms of Pharmacological Action'}, {'id': 'D020228', 'term': 'Pharmacologic Actions'}, {'id': 'D020164', 'term': 'Chemical Actions and Uses'}, {'id': 'D004232', 'term': 'Diuretics'}, {'id': 'D045283', 'term': 'Natriuretic Agents'}, {'id': 'D045505', 'term': 'Physiological Effects of Drugs'}, {'id': 'D013449', 'term': 'Sulfonamides'}, {'id': 'D000577', 'term': 'Amides'}, {'id': 'D062368', 'term': 'meta-Aminobenzoates'}, {'id': 'D062365', 'term': 'Aminobenzoates'}, {'id': 'D001565', 'term': 'Benzoates'}, {'id': 'D000146', 'term': 'Acids, Carbocyclic'}, {'id': 'D002264', 'term': 'Carboxylic Acids'}, {'id': 'D001555', 'term': 'Benzene Derivatives'}, {'id': 'D006841', 'term': 'Hydrocarbons, Aromatic'}, {'id': 'D006844', 'term': 'Hydrocarbons, Cyclic'}, {'id': 'D006838', 'term': 'Hydrocarbons'}, {'id': 'D013450', 'term': 'Sulfones'}, {'id': 'D007783', 'term': 'Lactones'}, {'id': 'D011283', 'term': 'Pregnenes'}, {'id': 'D011278', 'term': 'Pregnanes'}, {'id': 'D013256', 'term': 'Steroids'}, {'id': 'D000072473', 'term': 'Fused-Ring Compounds'}, {'id': 'D011083', 'term': 'Polycyclic Compounds'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'frederik.verbrugge@zol.be', 'phone': '0473924199', 'title': 'Dr. Frederik Verbrugge, researcher', 'phoneExt': '+32', 'organization': 'Ziekenhuis Oost-Limburg'}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': False}, 'limitationsAndCaveats': {'description': 'Slow recruitment: switch from monocentric to 2-center study; longer than anticipated duration of the study; eventually termination of the study after only 34 of the originally intended 80 patients had been included resulting in an underpowered study.'}}, 'adverseEventsModule': {'timeFrame': '6 months', 'description': 'Each patient was contacted by phone after 3 months, 6 months, and 12 months. A qualified study nurse assessed whether the patient died or was hospitalized during the previous 3 months. The electronic medical record was used to assess the reason for hospitalizations.', 'eventGroups': [{'id': 'EG000', 'title': 'Acetazolamide/Low-dose Loop Diuretics, Upfront Spironolactone', 'description': '* Patients receive 500 mg of intravenous acetazolamide immediately after randomization, with 250 mg intravenous acetazolamide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist.\n* Patients receive 2 mg of intravenous bumetanide immediately after randomization, with 1 mg intravenous bumetanide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist.\n* Patients receive open-label oral spironolactone at a dose of 25 mg unless serum potassium levels are \\>5 mmol/L.', 'otherNumAtRisk': 9, 'deathsNumAtRisk': 9, 'otherNumAffected': 6, 'seriousNumAtRisk': 9, 'deathsNumAffected': 6, 'seriousNumAffected': 3}, {'id': 'EG001', 'title': 'High-dose Loop Diuretics, Upfront Spironolactone', 'description': '* Patients receive the double of their daily maintenance dose of oral loop diuretics converted to mg bumetanide as an intravenous bolus after randomization.\n* Patients continue to receive this dose daily on the next 3 days divided between two administrations with at least a 6 h interval for as long as they are considered volume overloaded by the treating cardiologist.\n* Patients receive open-label oral spironolactone at a dose of 25 mg unless serum potassium levels are \\>5 mmol/L.', 'otherNumAtRisk': 7, 'deathsNumAtRisk': 7, 'otherNumAffected': 4, 'seriousNumAtRisk': 7, 'deathsNumAffected': 5, 'seriousNumAffected': 5}, {'id': 'EG002', 'title': 'Acetazolamide/Low-dose Loop Diuretics, no Spironolactone', 'description': '* Patients receive 500 mg of intravenous acetazolamide immediately after randomization, with 250 mg intravenous acetazolamide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist.\n* Patients receive 2 mg of intravenous bumetanide immediately after randomization, with 1 mg intravenous bumetanide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist.\n* Spironolactone use is prohibited during the first 72 h, but encouraged at discharge.', 'otherNumAtRisk': 9, 'deathsNumAtRisk': 9, 'otherNumAffected': 7, 'seriousNumAtRisk': 9, 'deathsNumAffected': 5, 'seriousNumAffected': 2}, {'id': 'EG003', 'title': 'High-dose Loop Diuretics, no Spironolactone', 'description': '* Patients receive the double of their daily maintenance dose of oral loop diuretics converted to mg bumetanide as an intravenous bolus after randomization.\n* Patients continue to receive this dose daily on the next 3 days divided between two administrations with at least a 6 h interval for as long as they are considered volume overloaded by the treating cardiologist.\n* Spironolactone use is prohibited during the first 72 h, but encouraged at discharge.', 'otherNumAtRisk': 9, 'deathsNumAtRisk': 9, 'otherNumAffected': 5, 'seriousNumAtRisk': 9, 'deathsNumAffected': 5, 'seriousNumAffected': 3}], 'otherEvents': [{'term': 'Metabolic acidosis', 'notes': 'Serum bicarbonate level \\<22.0 mEq/L during the 72 h treatment interval', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 7, 'numAffected': 3}, {'groupId': 'EG002', 'numAtRisk': 9, 'numAffected': 2}, {'groupId': 'EG003', 'numAtRisk': 9, 'numAffected': 3}], 'organSystem': 'Renal and urinary disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Moderate hyperkalemia', 'notes': 'Serum potassium level 5.1-6.5 mmol/L during the 72 h treatment interval', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 7, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 9, 'numAffected': 2}, {'groupId': 'EG003', 'numAtRisk': 9, 'numAffected': 0}], 'organSystem': 'Renal and urinary disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Hypokalemia', 'notes': 'Serum potassium level \\<3.5 mmol/L during the 72 h treatment interval', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 7, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 9, 'numAffected': 3}, {'groupId': 'EG003', 'numAtRisk': 9, 'numAffected': 2}], 'organSystem': 'Renal and urinary disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Worsening renal function', 'notes': 'Increase of the serum creatinine level \\>0.3 mg/dL during the 72 h treatment interval', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 7, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 9, 'numAffected': 3}, {'groupId': 'EG003', 'numAtRisk': 9, 'numAffected': 0}], 'organSystem': 'Renal and urinary disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Hypotension', 'notes': 'Mean arterial blood pressure \\<65 mmHg or systolic blood pressure \\<100 mmHg during the 72 h treatment interval', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 7, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 9, 'numAffected': 3}, {'groupId': 'EG003', 'numAtRisk': 9, 'numAffected': 3}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}], 'seriousEvents': [{'term': 'Hospital readmission due to heart failure', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 7, 'numAffected': 5}, {'groupId': 'EG002', 'numAtRisk': 9, 'numAffected': 2}, {'groupId': 'EG003', 'numAtRisk': 9, 'numAffected': 3}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Serious hyperkalemia', 'notes': 'Serum potassium level \\>6.5 mmol/L during the 72 h treatment interval', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 7, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 9, 'numAffected': 0}], 'organSystem': 'Renal and urinary disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Acetazolamide Arm: Natriuresis 24 h', 'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'OG000'}, {'value': '6', 'groupId': 'OG001'}, {'value': '9', 'groupId': 'OG002'}, {'value': '9', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': 'Acetazolamide/Low-dose Loop Diuretics, Upfront Spironolactone', 'description': '* Patients receive 500 mg of intravenous acetazolamide immediately after randomization, with 250 mg intravenous acetazolamide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist.\n* Patients receive 2 mg of intravenous bumetanide immediately after randomization, with 1 mg intravenous bumetanide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist.\n* Patients receive open-label oral spironolactone at a dose of 25 mg unless serum potassium levels are \\>5 mmol/L.'}, {'id': 'OG001', 'title': 'High-dose Loop Diuretics, Upfront Spironolactone', 'description': '* Patients receive the double of their daily maintenance dose of oral loop diuretics converted to mg bumetanide as an intravenous bolus after randomization.\n* Patients continue to receive this dose daily on the next 3 days divided between two administrations with at least a 6 h interval for as long as they are considered volume overloaded by the treating cardiologist.\n* Patients receive open-label oral spironolactone at a dose of 25 mg unless serum potassium levels are \\>5 mmol/L.'}, {'id': 'OG002', 'title': 'Acetazolamide/Low-dose Loop Diuretics, no Spironolactone', 'description': '* Patients receive 500 mg of intravenous acetazolamide immediately after randomization, with 250 mg intravenous acetazolamide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist.\n* Patients receive 2 mg of intravenous bumetanide immediately after randomization, with 1 mg intravenous bumetanide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist.\n* Spironolactone use is prohibited during the first 72 h, but encouraged at discharge.'}, {'id': 'OG003', 'title': 'High-dose Loop Diuretics, no Spironolactone', 'description': '* Patients receive the double of their daily maintenance dose of oral loop diuretics converted to mg bumetanide as an intravenous bolus after randomization.\n* Patients continue to receive this dose daily on the next 3 days divided between two administrations with at least a 6 h interval for as long as they are considered volume overloaded by the treating cardiologist.\n* Spironolactone use is prohibited during the first 72 h, but encouraged at discharge.'}], 'classes': [{'categories': [{'measurements': [{'value': '324', 'spread': '133', 'groupId': 'OG000'}, {'value': '300', 'spread': '165', 'groupId': 'OG001'}, {'value': '211', 'spread': '96', 'groupId': 'OG002'}, {'value': '190', 'spread': '91', 'groupId': 'OG003'}]}]}], 'analyses': [{'pValue': '0.515', 'groupIds': ['OG000', 'OG001', 'OG002', 'OG003'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '30', 'ciLowerLimit': '-63', 'ciUpperLimit': '123', 'pValueComment': 'Not adjusted for multiple comparisons', 'groupDescription': '2x2 factorial design: both acetazolamide groups together are compared with both high-dose loop diuretic groups together', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'MEAN', 'timeFrame': '24h', 'description': 'For the acetazolamide arm of the study, the primary end-point is total natriuresis after 24 h (mmol). To assess this, urine is collected for 24 h after the first administration of diuretics according to the study protocol and natriuresis is calculated as the total amount of diuresis (L) multiplied by the urinary sodium concentration (mmol/L). Subsequently, patients receiving acetazolamide and low-dose loop diuretics (both the groups with and without upfront spironolactone together) are compared to patients not receiving acetazolamide but high-dose loop diuretics instead (both the groups with or without upfront spironolactone together)', 'unitOfMeasure': 'mmol', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': '2 patients not analysed because of errors with 24 h urinary collection'}, {'type': 'PRIMARY', 'title': 'Spironolactone Arm: Incidence of Hypo- (Serum Potassium <3.5 mmol/L) or Hyperkalemia (Serum Potassium >5.0 mmol/L)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '7', 'groupId': 'OG001'}, {'value': '9', 'groupId': 'OG002'}, {'value': '9', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': 'Acetazolamide/Low-dose Loop Diuretics, Upfront Spironolactone', 'description': '* Patients receive 500 mg of intravenous acetazolamide immediately after randomization, with 250 mg intravenous acetazolamide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist.\n* Patients receive 2 mg of intravenous bumetanide immediately after randomization, with 1 mg intravenous bumetanide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist.\n* Patients receive open-label oral spironolactone at a dose of 25 mg unless serum potassium levels are \\>5 mmol/L.'}, {'id': 'OG001', 'title': 'High-dose Loop Diuretics, Upfront Spironolactone', 'description': '* Patients receive the double of their daily maintenance dose of oral loop diuretics converted to mg bumetanide as an intravenous bolus after randomization.\n* Patients continue to receive this dose daily on the next 3 days divided between two administrations with at least a 6 h interval for as long as they are considered volume overloaded by the treating cardiologist.\n* Patients receive open-label oral spironolactone at a dose of 25 mg unless serum potassium levels are \\>5 mmol/L.'}, {'id': 'OG002', 'title': 'Acetazolamide/Low-dose Loop Diuretics, no Spironolactone', 'description': '* Patients receive 500 mg of intravenous acetazolamide immediately after randomization, with 250 mg intravenous acetazolamide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist.\n* Patients receive 2 mg of intravenous bumetanide immediately after randomization, with 1 mg intravenous bumetanide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist.\n* Spironolactone use is prohibited during the first 72 h, but encouraged at discharge.'}, {'id': 'OG003', 'title': 'High-dose Loop Diuretics, no Spironolactone', 'description': '* Patients receive the double of their daily maintenance dose of oral loop diuretics converted to mg bumetanide as an intravenous bolus after randomization.\n* Patients continue to receive this dose daily on the next 3 days divided between two administrations with at least a 6 h interval for as long as they are considered volume overloaded by the treating cardiologist.\n* Spironolactone use is prohibited during the first 72 h, but encouraged at discharge.'}], 'classes': [{'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}, {'value': '2', 'groupId': 'OG001'}, {'value': '5', 'groupId': 'OG002'}, {'value': '2', 'groupId': 'OG003'}]}]}], 'analyses': [{'pValue': '0.270', 'groupIds': ['OG000', 'OG001', 'OG002', 'OG003'], 'paramType': 'Risk Difference (RD)', 'ciNumSides': 'TWO_SIDED', 'paramValue': '-0.2', 'pValueComment': 'Not adjusted for multiple comparisons', 'groupDescription': '2x2 factorial design: analysis according to spironolactone use', 'statisticalMethod': 'Fisher Exact', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': '72h', 'description': 'For the spironolactone arm of the study, the primary end-point is the incidence of either hypo- (serum potassium \\<3.5 mmol/L) or hyperkalemia (serum potassium \\>5.0 mmol/L) at any of 3 morning blood samples at consecutive days after randomization. Patients receiving upfront spironolactone (both the group receiving acetazolamide+low dose loop diuretics and the group receiving high-dose loop diuretic therapy) are compared with them receiving no spironolactone (both the group receiving acetazolamide+low dose loop diuretics and the group receiving high-dose loop diuretic therapy).', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'NT-proBNP Change After 72 h', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '7', 'groupId': 'OG001'}, {'value': '9', 'groupId': 'OG002'}, {'value': '9', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': 'Acetazolamide/Low-dose Loop Diuretics, Upfront Spironolactone', 'description': '* Patients receive 500 mg of intravenous acetazolamide immediately after randomization, with 250 mg intravenous acetazolamide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist.\n* Patients receive 2 mg of intravenous bumetanide immediately after randomization, with 1 mg intravenous bumetanide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist.\n* Patients receive open-label oral spironolactone at a dose of 25 mg unless serum potassium levels are \\>5 mmol/L.'}, {'id': 'OG001', 'title': 'High-dose Loop Diuretics, Upfront Spironolactone', 'description': '* Patients receive the double of their daily maintenance dose of oral loop diuretics converted to mg bumetanide as an intravenous bolus after randomization.\n* Patients continue to receive this dose daily on the next 3 days divided between two administrations with at least a 6 h interval for as long as they are considered volume overloaded by the treating cardiologist.\n* Patients receive open-label oral spironolactone at a dose of 25 mg unless serum potassium levels are \\>5 mmol/L.'}, {'id': 'OG002', 'title': 'Acetazolamide/Low-dose Loop Diuretics, no Spironolactone', 'description': '* Patients receive 500 mg of intravenous acetazolamide immediately after randomization, with 250 mg intravenous acetazolamide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist.\n* Patients receive 2 mg of intravenous bumetanide immediately after randomization, with 1 mg intravenous bumetanide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist.\n* Spironolactone use is prohibited during the first 72 h, but encouraged at discharge.'}, {'id': 'OG003', 'title': 'High-dose Loop Diuretics, no Spironolactone', 'description': '* Patients receive the double of their daily maintenance dose of oral loop diuretics converted to mg bumetanide as an intravenous bolus after randomization.\n* Patients continue to receive this dose daily on the next 3 days divided between two administrations with at least a 6 h interval for as long as they are considered volume overloaded by the treating cardiologist.\n* Spironolactone use is prohibited during the first 72 h, but encouraged at discharge.'}], 'classes': [{'categories': [{'measurements': [{'value': '-20', 'spread': '36', 'groupId': 'OG000'}, {'value': '-11', 'spread': '19', 'groupId': 'OG001'}, {'value': '-3', 'spread': '40', 'groupId': 'OG002'}, {'value': '-6', 'spread': '51', 'groupId': 'OG003'}]}]}], 'paramType': 'MEAN', 'timeFrame': '72h', 'description': 'Relative NT-proBNP change (%) after 72 h compared to baseline.', 'unitOfMeasure': 'percentage change from baseline', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Number of Participants With Worsening Renal Function', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '7', 'groupId': 'OG001'}, {'value': '9', 'groupId': 'OG002'}, {'value': '9', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': 'Acetazolamide/Low-dose Loop Diuretics, Upfront Spironolactone', 'description': '* Patients receive 500 mg of intravenous acetazolamide immediately after randomization, with 250 mg intravenous acetazolamide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist.\n* Patients receive 2 mg of intravenous bumetanide immediately after randomization, with 1 mg intravenous bumetanide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist.\n* Patients receive open-label oral spironolactone at a dose of 25 mg unless serum potassium levels are \\>5 mmol/L.'}, {'id': 'OG001', 'title': 'High-dose Loop Diuretics, Upfront Spironolactone', 'description': '* Patients receive the double of their daily maintenance dose of oral loop diuretics converted to mg bumetanide as an intravenous bolus after randomization.\n* Patients continue to receive this dose daily on the next 3 days divided between two administrations with at least a 6 h interval for as long as they are considered volume overloaded by the treating cardiologist.\n* Patients receive open-label oral spironolactone at a dose of 25 mg unless serum potassium levels are \\>5 mmol/L.'}, {'id': 'OG002', 'title': 'Acetazolamide/Low-dose Loop Diuretics, no Spironolactone', 'description': '* Patients receive 500 mg of intravenous acetazolamide immediately after randomization, with 250 mg intravenous acetazolamide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist.\n* Patients receive 2 mg of intravenous bumetanide immediately after randomization, with 1 mg intravenous bumetanide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist.\n* Spironolactone use is prohibited during the first 72 h, but encouraged at discharge.'}, {'id': 'OG003', 'title': 'High-dose Loop Diuretics, no Spironolactone', 'description': '* Patients receive the double of their daily maintenance dose of oral loop diuretics converted to mg bumetanide as an intravenous bolus after randomization.\n* Patients continue to receive this dose daily on the next 3 days divided between two administrations with at least a 6 h interval for as long as they are considered volume overloaded by the treating cardiologist.\n* Spironolactone use is prohibited during the first 72 h, but encouraged at discharge.'}], 'classes': [{'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}, {'value': '3', 'groupId': 'OG002'}, {'value': '0', 'groupId': 'OG003'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': '72h', 'description': 'Worsening renal function is defined as a rise in serum creatine \\>0.3 mg/dL or a \\>20% decrease in estimated glomerular filtration rate by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula compared to baseline at any time point before 72 h. Serum creatinine values are assessed at three consecutive mornings after study inclusion.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Persistent Renal Impairment', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}, {'value': '2', 'groupId': 'OG001'}, {'value': '5', 'groupId': 'OG002'}, {'value': '4', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': 'Acetazolamide/Low-dose Loop Diuretics, Upfront Spironolactone', 'description': '* Patients receive 500 mg of intravenous acetazolamide immediately after randomization, with 250 mg intravenous acetazolamide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist.\n* Patients receive 2 mg of intravenous bumetanide immediately after randomization, with 1 mg intravenous bumetanide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist.\n* Patients receive open-label oral spironolactone at a dose of 25 mg unless serum potassium levels are \\>5 mmol/L.'}, {'id': 'OG001', 'title': 'High-dose Loop Diuretics, Upfront Spironolactone', 'description': '* Patients receive the double of their daily maintenance dose of oral loop diuretics converted to mg bumetanide as an intravenous bolus after randomization.\n* Patients continue to receive this dose daily on the next 3 days divided between two administrations with at least a 6 h interval for as long as they are considered volume overloaded by the treating cardiologist.\n* Patients receive open-label oral spironolactone at a dose of 25 mg unless serum potassium levels are \\>5 mmol/L.'}, {'id': 'OG002', 'title': 'Acetazolamide/Low-dose Loop Diuretics, no Spironolactone', 'description': '* Patients receive 500 mg of intravenous acetazolamide immediately after randomization, with 250 mg intravenous acetazolamide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist.\n* Patients receive 2 mg of intravenous bumetanide immediately after randomization, with 1 mg intravenous bumetanide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist.\n* Spironolactone use is prohibited during the first 72 h, but encouraged at discharge.'}, {'id': 'OG003', 'title': 'High-dose Loop Diuretics, no Spironolactone', 'description': '* Patients receive the double of their daily maintenance dose of oral loop diuretics converted to mg bumetanide as an intravenous bolus after randomization.\n* Patients continue to receive this dose daily on the next 3 days divided between two administrations with at least a 6 h interval for as long as they are considered volume overloaded by the treating cardiologist.\n* Spironolactone use is prohibited during the first 72 h, but encouraged at discharge.'}], 'classes': [{'categories': [{'measurements': [{'value': '3', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}, {'value': '0', 'groupId': 'OG002'}, {'value': '1', 'groupId': 'OG003'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': '4 weeks after hospital discharge', 'description': 'Persistent renal impairment is defined as a persistently elevated serum creatine \\>0.3mg/dL or \\>20% decrease in estimated glomerular filtration rate by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula, above the baseline value of the patient and will be assessed on a scheduled follow-up appointment 4 weeks after hospital discharge.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': '9 patients died or were too sick for follow-up appointment; 9 refused a venous blood sample at the follow-up appointment (protocol violation)'}, {'type': 'SECONDARY', 'title': 'Peak Plasma Aldosterone Concentration After 72 h', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '7', 'groupId': 'OG001'}, {'value': '9', 'groupId': 'OG002'}, {'value': '9', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': 'Acetazolamide/Low-dose Loop Diuretics, Upfront Spironolactone', 'description': '* Patients receive 500 mg of intravenous acetazolamide immediately after randomization, with 250 mg intravenous acetazolamide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist.\n* Patients receive 2 mg of intravenous bumetanide immediately after randomization, with 1 mg intravenous bumetanide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist.\n* Patients receive open-label oral spironolactone at a dose of 25 mg unless serum potassium levels are \\>5 mmol/L.'}, {'id': 'OG001', 'title': 'High-dose Loop Diuretics, Upfront Spironolactone', 'description': '* Patients receive the double of their daily maintenance dose of oral loop diuretics converted to mg bumetanide as an intravenous bolus after randomization.\n* Patients continue to receive this dose daily on the next 3 days divided between two administrations with at least a 6 h interval for as long as they are considered volume overloaded by the treating cardiologist.\n* Patients receive open-label oral spironolactone at a dose of 25 mg unless serum potassium levels are \\>5 mmol/L.'}, {'id': 'OG002', 'title': 'Acetazolamide/Low-dose Loop Diuretics, no Spironolactone', 'description': '* Patients receive 500 mg of intravenous acetazolamide immediately after randomization, with 250 mg intravenous acetazolamide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist.\n* Patients receive 2 mg of intravenous bumetanide immediately after randomization, with 1 mg intravenous bumetanide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist.\n* Spironolactone use is prohibited during the first 72 h, but encouraged at discharge.'}, {'id': 'OG003', 'title': 'High-dose Loop Diuretics, no Spironolactone', 'description': '* Patients receive the double of their daily maintenance dose of oral loop diuretics converted to mg bumetanide as an intravenous bolus after randomization.\n* Patients continue to receive this dose daily on the next 3 days divided between two administrations with at least a 6 h interval for as long as they are considered volume overloaded by the treating cardiologist.\n* Spironolactone use is prohibited during the first 72 h, but encouraged at discharge.'}], 'classes': [{'categories': [{'measurements': [{'value': '196', 'groupId': 'OG000', 'lowerLimit': '127', 'upperLimit': '338'}, {'value': '234', 'groupId': 'OG001', 'lowerLimit': '149', 'upperLimit': '334'}, {'value': '302', 'groupId': 'OG002', 'lowerLimit': '165', 'upperLimit': '909'}, {'value': '204', 'groupId': 'OG003', 'lowerLimit': '153', 'upperLimit': '756'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': '72h', 'description': 'At three consecutive mornings after study inclusion, blood samples will be taken to assess plasma aldosterone levels. The highest value will constitute the peak plasma aldosterone concentration (ng/L).', 'unitOfMeasure': 'ng/L', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Peak Plasma Renin Activity After 72 h', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '7', 'groupId': 'OG001'}, {'value': '9', 'groupId': 'OG002'}, {'value': '9', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': 'Acetazolamide/Low-dose Loop Diuretics, Upfront Spironolactone', 'description': '* Patients receive 500 mg of intravenous acetazolamide immediately after randomization, with 250 mg intravenous acetazolamide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist.\n* Patients receive 2 mg of intravenous bumetanide immediately after randomization, with 1 mg intravenous bumetanide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist.\n* Patients receive open-label oral spironolactone at a dose of 25 mg unless serum potassium levels are \\>5 mmol/L.'}, {'id': 'OG001', 'title': 'High-dose Loop Diuretics, Upfront Spironolactone', 'description': '* Patients receive the double of their daily maintenance dose of oral loop diuretics converted to mg bumetanide as an intravenous bolus after randomization.\n* Patients continue to receive this dose daily on the next 3 days divided between two administrations with at least a 6 h interval for as long as they are considered volume overloaded by the treating cardiologist.\n* Patients receive open-label oral spironolactone at a dose of 25 mg unless serum potassium levels are \\>5 mmol/L.'}, {'id': 'OG002', 'title': 'Acetazolamide/Low-dose Loop Diuretics, no Spironolactone', 'description': '* Patients receive 500 mg of intravenous acetazolamide immediately after randomization, with 250 mg intravenous acetazolamide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist.\n* Patients receive 2 mg of intravenous bumetanide immediately after randomization, with 1 mg intravenous bumetanide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist.\n* Spironolactone use is prohibited during the first 72 h, but encouraged at discharge.'}, {'id': 'OG003', 'title': 'High-dose Loop Diuretics, no Spironolactone', 'description': '* Patients receive the double of their daily maintenance dose of oral loop diuretics converted to mg bumetanide as an intravenous bolus after randomization.\n* Patients continue to receive this dose daily on the next 3 days divided between two administrations with at least a 6 h interval for as long as they are considered volume overloaded by the treating cardiologist.\n* Spironolactone use is prohibited during the first 72 h, but encouraged at discharge.'}], 'classes': [{'categories': [{'measurements': [{'value': '3.8', 'groupId': 'OG000', 'lowerLimit': '0.9', 'upperLimit': '6.5'}, {'value': '5.0', 'groupId': 'OG001', 'lowerLimit': '3.8', 'upperLimit': '10.2'}, {'value': '12.0', 'groupId': 'OG002', 'lowerLimit': '0.8', 'upperLimit': '34.3'}, {'value': '2.5', 'groupId': 'OG003', 'lowerLimit': '0.8', 'upperLimit': '28.2'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': '72h', 'description': 'At three consecutive mornings after study inclusion, blood samples will be taken to assess plasma renin activity. The highest value will constitute the peak plasma renin activity (ng/mL/h).', 'unitOfMeasure': 'µg/L/h', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Natriuresis 48 h', 'timeFrame': '48h', 'description': 'Total natriuresis (mmol) after 48 h.', 'reportingStatus': 'NOT_POSTED', 'denomUnitsSelected': 'Participants'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Natriuresis 72 h', 'timeFrame': '72h', 'description': 'Total natriuresis (mmol) after 72 h.', 'reportingStatus': 'NOT_POSTED', 'denomUnitsSelected': 'Participants'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Diuresis 24 h', 'timeFrame': '24h', 'description': 'Total amount of urine output (L) after 24 h.', 'reportingStatus': 'NOT_POSTED', 'denomUnitsSelected': 'Participants'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Diuresis 48 h', 'timeFrame': '48h', 'description': 'Total amount of urine output (L) after 48 h.', 'reportingStatus': 'NOT_POSTED', 'denomUnitsSelected': 'Participants'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Diuresis 72 h', 'timeFrame': '72h', 'description': 'Total amount of urine output (L) after 72 h.', 'reportingStatus': 'NOT_POSTED', 'denomUnitsSelected': 'Participants'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Weight Change After 72 h', 'timeFrame': '72h', 'description': 'Body weight change after 72 h compared to admission.', 'reportingStatus': 'NOT_POSTED', 'denomUnitsSelected': 'Participants'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Visual Analogue Scale Score for Dyspnea After 24 h', 'timeFrame': '24h', 'description': 'Scale name and construct: Visual analogue scale presented as a line with a movable indicator. Far left of the line indicates no dyspnea at all and far right of the line indicates the worst imaginable dyspnea. The participant can move the indicator to one certain point among the line and the investigator can read at the back a number going from 0 to 100 with 0 indicating no dyspnea and 100 the worst imaginable dyspnea.', 'reportingStatus': 'NOT_POSTED', 'denomUnitsSelected': 'Participants'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Visual Analogue Scale Score for Dyspnea After 48 h', 'timeFrame': '48h', 'reportingStatus': 'NOT_POSTED', 'denomUnitsSelected': 'Participants'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Visual Analogue Scale Score for Dyspnea After 72 h', 'timeFrame': '72h', 'reportingStatus': 'NOT_POSTED', 'denomUnitsSelected': 'Participants'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': '4-point Likert Scale for Edema After 24 h', 'timeFrame': '24h', 'reportingStatus': 'NOT_POSTED', 'denomUnitsSelected': 'Participants'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': '4-point Likert Scale for Edema After 48 h', 'timeFrame': '48h', 'reportingStatus': 'NOT_POSTED', 'denomUnitsSelected': 'Participants'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': '4-point Likert Scale for Edema After 72 h', 'timeFrame': '72h', 'reportingStatus': 'NOT_POSTED', 'denomUnitsSelected': 'Participants'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Incidence of Therapy-refractory Congestion', 'timeFrame': '72h', 'description': 'Need for combinational diuretic therapy with thiazide-type diuretics, bail-out ultrafiltration or renal replacement therapy', 'reportingStatus': 'NOT_POSTED', 'denomUnitsSelected': 'Participants'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'All-cause Mortality', 'timeFrame': 'After 1 year of follow-up', 'reportingStatus': 'NOT_POSTED', 'denomUnitsSelected': 'Participants'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Acetazolamide/Low-dose Loop Diuretics, Upfront Spironolactone', 'description': '* Patients receive 500 mg of intravenous acetazolamide immediately after randomization, with 250 mg intravenous acetazolamide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist.\n* Patients receive 2 mg of intravenous bumetanide immediately after randomization, with 1 mg intravenous bumetanide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist.\n* Patients receive open-label oral spironolactone at a dose of 25 mg unless serum potassium levels are \\>5 mmol/L.'}, {'id': 'FG001', 'title': 'High-dose Loop Diuretics, Upfront Spironolactone', 'description': '* Patients receive the double of their daily maintenance dose of oral loop diuretics converted to mg bumetanide as an intravenous bolus after randomization.\n* Patients continue to receive this dose daily on the next 3 days divided between two administrations with at least a 6 h interval for as long as they are considered volume overloaded by the treating cardiologist.\n* Patients receive open-label oral spironolactone at a dose of 25 mg unless serum potassium levels are \\>5 mmol/L.'}, {'id': 'FG002', 'title': 'Acetazolamide/Low-dose Loop Diuretics, no Spironolactone', 'description': '* Patients receive 500 mg of intravenous acetazolamide immediately after randomization, with 250 mg intravenous acetazolamide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist.\n* Patients receive 2 mg of intravenous bumetanide immediately after randomization, with 1 mg intravenous bumetanide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist.\n* Spironolactone use is prohibited during the first 72 h, but encouraged at discharge.'}, {'id': 'FG003', 'title': 'High-dose Loop Diuretics, no Spironolactone', 'description': '* Patients receive the double of their daily maintenance dose of oral loop diuretics converted to mg bumetanide as an intravenous bolus after randomization.\n* Patients continue to receive this dose daily on the next 3 days divided between two administrations with at least a 6 h interval for as long as they are considered volume overloaded by the treating cardiologist.\n* Spironolactone use is prohibited during the first 72 h, but encouraged at discharge.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '9'}, {'groupId': 'FG001', 'numSubjects': '7'}, {'groupId': 'FG002', 'numSubjects': '9'}, {'groupId': 'FG003', 'numSubjects': '9'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '9'}, {'groupId': 'FG001', 'numSubjects': '7'}, {'groupId': 'FG002', 'numSubjects': '9'}, {'groupId': 'FG003', 'numSubjects': '9'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '0'}, {'groupId': 'FG003', 'numSubjects': '0'}]}]}], 'recruitmentDetails': '* Dates of the recruitment period: 28/12/2013 till 14/03/2017\n* location: emergency services and outpatient cardiology clinic of 2 tertiary care centers (Ziekenhuis Oost-Limburg, Genk, Belgium \\& UZ Leuven, Leuven, Belgium)', 'preAssignmentDetails': 'None, every patient that was enrolled was immediately randomised and started with the protocol of the study.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'BG000'}, {'value': '7', 'groupId': 'BG001'}, {'value': '9', 'groupId': 'BG002'}, {'value': '9', 'groupId': 'BG003'}, {'value': '34', 'groupId': 'BG004'}]}], 'groups': [{'id': 'BG000', 'title': 'Acetazolamide/Low-dose Loop Diuretics, Upfront Spironolactone', 'description': '* Patients receive 500 mg of intravenous acetazolamide immediately after randomization, with 250 mg intravenous acetazolamide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist.\n* Patients receive 2 mg of intravenous bumetanide immediately after randomization, with 1 mg intravenous bumetanide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist.\n* Patients receive open-label oral spironolactone at a dose of 25 mg unless serum potassium levels are \\>5 mmol/L.'}, {'id': 'BG001', 'title': 'High-dose Loop Diuretics, Upfront Spironolactone', 'description': '* Patients receive the double of their daily maintenance dose of oral loop diuretics converted to mg bumetanide as an intravenous bolus after randomization.\n* Patients continue to receive this dose daily on the next 3 days divided between two administrations with at least a 6 h interval for as long as they are considered volume overloaded by the treating cardiologist.\n* Patients receive open-label oral spironolactone at a dose of 25 mg unless serum potassium levels are \\>5 mmol/L.'}, {'id': 'BG002', 'title': 'Acetazolamide/Low-dose Loop Diuretics, no Spironolactone', 'description': '* Patients receive 500 mg of intravenous acetazolamide immediately after randomization, with 250 mg intravenous acetazolamide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist.\n* Patients receive 2 mg of intravenous bumetanide immediately after randomization, with 1 mg intravenous bumetanide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist.\n* Spironolactone use is prohibited during the first 72 h, but encouraged at discharge'}, {'id': 'BG003', 'title': 'High-dose Loop Diuretics, no Spironolactone', 'description': '* Patients receive the double of their daily maintenance dose of oral loop diuretics converted to mg bumetanide as an intravenous bolus after randomization.\n* Patients continue to receive this dose daily on the next 3 days divided between two administrations with at least a 6 h interval for as long as they are considered volume overloaded by the treating cardiologist.\n* Spironolactone use is prohibited during the first 72 h, but encouraged at discharge'}, {'id': 'BG004', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '81', 'spread': '8', 'groupId': 'BG000'}, {'value': '75', 'spread': '7', 'groupId': 'BG001'}, {'value': '81', 'spread': '5', 'groupId': 'BG002'}, {'value': '81', 'spread': '7', 'groupId': 'BG003'}, {'value': '80', 'spread': '7', 'groupId': 'BG004'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '2', 'groupId': 'BG000'}, {'value': '2', 'groupId': 'BG001'}, {'value': '5', 'groupId': 'BG002'}, {'value': '3', 'groupId': 'BG003'}, {'value': '12', 'groupId': 'BG004'}]}, {'title': 'Male', 'measurements': [{'value': '7', 'groupId': 'BG000'}, {'value': '5', 'groupId': 'BG001'}, {'value': '4', 'groupId': 'BG002'}, {'value': '6', 'groupId': 'BG003'}, {'value': '22', 'groupId': 'BG004'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '0', 'groupId': 'BG003'}, {'value': '0', 'groupId': 'BG004'}]}, {'title': 'Asian', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '0', 'groupId': 'BG003'}, {'value': '0', 'groupId': 'BG004'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '0', 'groupId': 'BG003'}, {'value': '0', 'groupId': 'BG004'}]}, {'title': 'Black or African American', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '0', 'groupId': 'BG003'}, {'value': '0', 'groupId': 'BG004'}]}, {'title': 'White', 'measurements': [{'value': '9', 'groupId': 'BG000'}, {'value': '7', 'groupId': 'BG001'}, {'value': '9', 'groupId': 'BG002'}, {'value': '9', 'groupId': 'BG003'}, {'value': '34', 'groupId': 'BG004'}]}, {'title': 'More than one race', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '0', 'groupId': 'BG003'}, {'value': '0', 'groupId': 'BG004'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '0', 'groupId': 'BG003'}, {'value': '0', 'groupId': 'BG004'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'Belgium', 'categories': [{'measurements': [{'value': '9', 'groupId': 'BG000'}, {'value': '7', 'groupId': 'BG001'}, {'value': '9', 'groupId': 'BG002'}, {'value': '9', 'groupId': 'BG003'}, {'value': '34', 'groupId': 'BG004'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'New York Heart Association functional class', 'classes': [{'categories': [{'title': 'II', 'measurements': [{'value': '2', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '1', 'groupId': 'BG003'}, {'value': '3', 'groupId': 'BG004'}]}, {'title': 'III', 'measurements': [{'value': '5', 'groupId': 'BG000'}, {'value': '3', 'groupId': 'BG001'}, {'value': '7', 'groupId': 'BG002'}, {'value': '4', 'groupId': 'BG003'}, {'value': '19', 'groupId': 'BG004'}]}, {'title': 'IV', 'measurements': [{'value': '2', 'groupId': 'BG000'}, {'value': '4', 'groupId': 'BG001'}, {'value': '2', 'groupId': 'BG002'}, {'value': '4', 'groupId': 'BG003'}, {'value': '12', 'groupId': 'BG004'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'History of ischemic heart disease', 'classes': [{'categories': [{'measurements': [{'value': '5', 'groupId': 'BG000'}, {'value': '6', 'groupId': 'BG001'}, {'value': '3', 'groupId': 'BG002'}, {'value': '7', 'groupId': 'BG003'}, {'value': '21', 'groupId': 'BG004'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'History of atrial fibrillation', 'classes': [{'categories': [{'measurements': [{'value': '3', 'groupId': 'BG000'}, {'value': '4', 'groupId': 'BG001'}, {'value': '7', 'groupId': 'BG002'}, {'value': '6', 'groupId': 'BG003'}, {'value': '20', 'groupId': 'BG004'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'History of diabetes', 'classes': [{'categories': [{'measurements': [{'value': '3', 'groupId': 'BG000'}, {'value': '2', 'groupId': 'BG001'}, {'value': '2', 'groupId': 'BG002'}, {'value': '3', 'groupId': 'BG003'}, {'value': '10', 'groupId': 'BG004'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Estimated glomerular filtration rate', 'classes': [{'categories': [{'measurements': [{'value': '36', 'spread': '17', 'groupId': 'BG000'}, {'value': '32', 'spread': '9', 'groupId': 'BG001'}, {'value': '35', 'spread': '16', 'groupId': 'BG002'}, {'value': '40', 'spread': '31', 'groupId': 'BG003'}, {'value': '36', 'spread': '20', 'groupId': 'BG004'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'mL/min/1.73m²', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Renin-angiotensin blocker therapy', 'classes': [{'categories': [{'measurements': [{'value': '2', 'groupId': 'BG000'}, {'value': '4', 'groupId': 'BG001'}, {'value': '5', 'groupId': 'BG002'}, {'value': '3', 'groupId': 'BG003'}, {'value': '14', 'groupId': 'BG004'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Beta-blocker therapy', 'classes': [{'categories': [{'measurements': [{'value': '8', 'groupId': 'BG000'}, {'value': '7', 'groupId': 'BG001'}, {'value': '8', 'groupId': 'BG002'}, {'value': '8', 'groupId': 'BG003'}, {'value': '31', 'groupId': 'BG004'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2015-08-27', 'size': 881126, 'label': 'Study Protocol and Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'Prot_SAP_000.pdf', 'typeAbbrev': 'Prot_SAP', 'uploadDate': '2018-12-08T09:42', 'hasProtocol': True}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'FACTORIAL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 34}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2013-11', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2019-05', 'completionDateStruct': {'date': '2017-10', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2019-05-11', 'studyFirstSubmitDate': '2013-10-25', 'resultsFirstSubmitDate': '2018-02-10', 'studyFirstSubmitQcDate': '2013-10-25', 'lastUpdatePostDateStruct': {'date': '2019-05-21', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2018-12-08', 'studyFirstPostDateStruct': {'date': '2013-10-31', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2019-03-21', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2017-04', 'type': 'ACTUAL'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Natriuresis 48 h', 'timeFrame': '48h', 'description': 'Total natriuresis (mmol) after 48 h.'}, {'measure': 'Natriuresis 72 h', 'timeFrame': '72h', 'description': 'Total natriuresis (mmol) after 72 h.'}, {'measure': 'Diuresis 24 h', 'timeFrame': '24h', 'description': 'Total amount of urine output (L) after 24 h.'}, {'measure': 'Diuresis 48 h', 'timeFrame': '48h', 'description': 'Total amount of urine output (L) after 48 h.'}, {'measure': 'Diuresis 72 h', 'timeFrame': '72h', 'description': 'Total amount of urine output (L) after 72 h.'}, {'measure': 'Weight Change After 72 h', 'timeFrame': '72h', 'description': 'Body weight change after 72 h compared to admission.'}, {'measure': 'Visual Analogue Scale Score for Dyspnea After 24 h', 'timeFrame': '24h', 'description': 'Scale name and construct: Visual analogue scale presented as a line with a movable indicator. Far left of the line indicates no dyspnea at all and far right of the line indicates the worst imaginable dyspnea. The participant can move the indicator to one certain point among the line and the investigator can read at the back a number going from 0 to 100 with 0 indicating no dyspnea and 100 the worst imaginable dyspnea.'}, {'measure': 'Visual Analogue Scale Score for Dyspnea After 48 h', 'timeFrame': '48h'}, {'measure': 'Visual Analogue Scale Score for Dyspnea After 72 h', 'timeFrame': '72h'}, {'measure': '4-point Likert Scale for Edema After 24 h', 'timeFrame': '24h'}, {'measure': '4-point Likert Scale for Edema After 48 h', 'timeFrame': '48h'}, {'measure': '4-point Likert Scale for Edema After 72 h', 'timeFrame': '72h'}, {'measure': 'Incidence of Therapy-refractory Congestion', 'timeFrame': '72h', 'description': 'Need for combinational diuretic therapy with thiazide-type diuretics, bail-out ultrafiltration or renal replacement therapy'}, {'measure': 'All-cause Mortality', 'timeFrame': 'After 1 year of follow-up'}], 'primaryOutcomes': [{'measure': 'Acetazolamide Arm: Natriuresis 24 h', 'timeFrame': '24h', 'description': 'For the acetazolamide arm of the study, the primary end-point is total natriuresis after 24 h (mmol). To assess this, urine is collected for 24 h after the first administration of diuretics according to the study protocol and natriuresis is calculated as the total amount of diuresis (L) multiplied by the urinary sodium concentration (mmol/L). Subsequently, patients receiving acetazolamide and low-dose loop diuretics (both the groups with and without upfront spironolactone together) are compared to patients not receiving acetazolamide but high-dose loop diuretics instead (both the groups with or without upfront spironolactone together)'}, {'measure': 'Spironolactone Arm: Incidence of Hypo- (Serum Potassium <3.5 mmol/L) or Hyperkalemia (Serum Potassium >5.0 mmol/L)', 'timeFrame': '72h', 'description': 'For the spironolactone arm of the study, the primary end-point is the incidence of either hypo- (serum potassium \\<3.5 mmol/L) or hyperkalemia (serum potassium \\>5.0 mmol/L) at any of 3 morning blood samples at consecutive days after randomization. Patients receiving upfront spironolactone (both the group receiving acetazolamide+low dose loop diuretics and the group receiving high-dose loop diuretic therapy) are compared with them receiving no spironolactone (both the group receiving acetazolamide+low dose loop diuretics and the group receiving high-dose loop diuretic therapy).'}], 'secondaryOutcomes': [{'measure': 'NT-proBNP Change After 72 h', 'timeFrame': '72h', 'description': 'Relative NT-proBNP change (%) after 72 h compared to baseline.'}, {'measure': 'Number of Participants With Worsening Renal Function', 'timeFrame': '72h', 'description': 'Worsening renal function is defined as a rise in serum creatine \\>0.3 mg/dL or a \\>20% decrease in estimated glomerular filtration rate by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula compared to baseline at any time point before 72 h. Serum creatinine values are assessed at three consecutive mornings after study inclusion.'}, {'measure': 'Persistent Renal Impairment', 'timeFrame': '4 weeks after hospital discharge', 'description': 'Persistent renal impairment is defined as a persistently elevated serum creatine \\>0.3mg/dL or \\>20% decrease in estimated glomerular filtration rate by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula, above the baseline value of the patient and will be assessed on a scheduled follow-up appointment 4 weeks after hospital discharge.'}, {'measure': 'Peak Plasma Aldosterone Concentration After 72 h', 'timeFrame': '72h', 'description': 'At three consecutive mornings after study inclusion, blood samples will be taken to assess plasma aldosterone levels. The highest value will constitute the peak plasma aldosterone concentration (ng/L).'}, {'measure': 'Peak Plasma Renin Activity After 72 h', 'timeFrame': '72h', 'description': 'At three consecutive mornings after study inclusion, blood samples will be taken to assess plasma renin activity. The highest value will constitute the peak plasma renin activity (ng/mL/h).'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['acetazolamide', 'bumetanide', 'cardio-renal syndrome', 'diuretics', 'heart failure', 'natriuresis', 'spironolactone'], 'conditions': ['Heart Failure']}, 'referencesModule': {'references': [{'pmid': '29587582', 'type': 'RESULT', 'citation': 'Verbrugge FH, Martens P, Ameloot K, Haemels V, Penders J, Dupont M, Tang WHW, Droogne W, Mullens W. Spironolactone to increase natriuresis in congestive heart failure with cardiorenal syndrome. Acta Cardiol. 2019 Apr;74(2):100-107. doi: 10.1080/00015385.2018.1455947. Epub 2018 Mar 27.'}, {'pmid': '31074184', 'type': 'RESULT', 'citation': 'Verbrugge FH, Martens P, Ameloot K, Haemels V, Penders J, Dupont M, Tang WHW, Droogne W, Mullens W. Acetazolamide to increase natriuresis in congestive heart failure at high risk for diuretic resistance. Eur J Heart Fail. 2019 Nov;21(11):1415-1422. doi: 10.1002/ejhf.1478. Epub 2019 May 9.'}]}, 'descriptionModule': {'briefSummary': 'This study has two primary objectives:\n\n1. To compare combination therapy with acetazolamide and low-dose loop diuretics versus high-dose loop diuretics (standard of care) in patients with acute decompensated heart failure at high risk for diuretic resistance.\n2. To demonstrate the safety and efficacy of upfront therapy with spironolactone in addition to loop diuretic therapy in patients with acute decompensated heart failure at high risk for diuretic resistance.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Older than 18 years and able to give informed consent\n* Clinical diagnosis of acute decompensated heart failure within the previous 8 h\n* At least two clinical signs of congestion (edema, ascites, jugular venous distension, or pulmonary vascular congestion on chest radiography)\n* Maintenance therapy with oral loop diuretics at a dose of at least 1 mg bumetanide (1 mg bumetanide = 40 mg furosemide = 20 mg torsemide) for at least 1 month before hospital admission\n* NT-proBNP \\>1000 ng/L\n* Left ventricular ejection fraction \\<50%\n* At least one out of three of the following criteria:\n\n * Serum sodium \\<136 mmol/L\n * Serum urea/creatinine ratio \\>50 (comparable to a BUN/creatinine ratio \\>25)\n * Admission serum creatinine increased with \\>0.3 mg/dL compared to previous value within 3 months before admission\n\nExclusion Criteria:\n\n* History of cardiac transplantation and/or ventricular assist device\n* Concurrent diagnosis of an acute coronary syndrome defined as typical chest pain and/or electrocardiographic changes in addition to a troponin rise \\>99th percentile\n* Mean arterial blood pressure \\<65 mmHg, or systolic blood pressure \\<90 mmHg at the moment of admission\n* Use of intravenous inotropes, vasopressors or nitroprusside at any time point during the study\n* A baseline estimated glomerular filtration rate \\<15 mL/min/1.73m² according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula at the moment of inclusion\n* Use of renal replacement therapy or ultrafiltration before study inclusion\n* Treatment with acetazolamide within the previous month\n* Treatment with ≥2 mg bumetanide or an equivalent dose during the index hospitalization before randomization\n* Use of diuretics, vasopressin antagonists or mineralocorticoid receptor antagonist not specified by the protocol\n* Exposure to nephrotoxic agents (i.e. contrast dye) anticipated within 3 days'}, 'identificationModule': {'nctId': 'NCT01973335', 'acronym': 'DIURESIS-CHF', 'briefTitle': 'Acetazolamide and Spironolactone to Increase Natriuresis in Congestive Heart Failure', 'organization': {'class': 'OTHER', 'fullName': 'Hasselt University'}, 'officialTitle': 'Diamox/Aldactone to Increase the URinary Excretion of Sodium: an Investigational Study in Congestive Heart Failure', 'orgStudyIdInfo': {'id': 'ZOL-DIURESIS-CHF'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Acetazolamide/low-dose loop diuretics, upfront spironolactone', 'description': '2x2 factorial design: This group is the experimental group for both study interventions (acetazolamide and upfront spironolactone).\n\nSee interventions for more details.', 'interventionNames': ['Drug: Combination therapy with acetazolamide and low-dose loop diuretics', 'Drug: Upfront therapy with oral spironolactone']}, {'type': 'EXPERIMENTAL', 'label': 'High-dose loop diuretics, upfront spironolactone', 'description': '2x2 factorial design: This group is the experimental group for the study intervention with upfront spironolactone. This group receives high-dose loop diuretics as an active comparator to the study intervention with acetazolamide.\n\nSee interventions for more details.', 'interventionNames': ['Drug: High-dose loop diuretics', 'Drug: Upfront therapy with oral spironolactone']}, {'type': 'EXPERIMENTAL', 'label': 'Acetazolamide/low-dose loop diuretics, no spironolactone', 'description': '2x2 factorial design: This group is the experimental group for the study intervention with acetazolamide. This group receives no intervention with regards to the spironolactone arm.\n\nSee interventions for more details.', 'interventionNames': ['Drug: Combination therapy with acetazolamide and low-dose loop diuretics']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'High-dose loop diuretics, no spironolactone', 'description': '2x2 factorial design: This group receives high-dose loop diuretics as an active comparator to the study intervention with acetazolamide. This group receives no intervention with regards to the spironolactone arm.\n\nSee interventions for more details.', 'interventionNames': ['Drug: High-dose loop diuretics']}], 'interventions': [{'name': 'Combination therapy with acetazolamide and low-dose loop diuretics', 'type': 'DRUG', 'otherNames': ['Diamox (acetazolamide)', 'Burinex/Bumex (loop diuretics)'], 'description': '* Patients receive 500 mg of intravenous acetazolamide immediately after randomization, with 250 mg intravenous acetazolamide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist.\n* Patients receive 2 mg of intravenous bumetanide immediately after randomization, with 1 mg intravenous bumetanide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist.\n* If diuresis \\<1,5 L while the patient is still considered volume overloaded by his/her treating cardiologist, the dose of acetazolamide is maintained at 500 mg and the dose of bumetanide is maintained at 2mg.\n\nIn case of therapy-refractory congestion, treatment is at the discretion of the treating physician, but addition of chlorthalidone 50 mg PO is recommended by the investigators as a first-line option.', 'armGroupLabels': ['Acetazolamide/low-dose loop diuretics, no spironolactone', 'Acetazolamide/low-dose loop diuretics, upfront spironolactone']}, {'name': 'High-dose loop diuretics', 'type': 'DRUG', 'otherNames': ['Burinex/Bumex'], 'description': '* Patients receive the double of their daily maintenance dose of oral loop diuretics converted to mg bumetanide as an intravenous bolus after randomization.\n* Patients continue to receive this dose daily on the next 3 days divided between two administrations with at least a 6 h interval for as long as they are considered volume overloaded by the treating cardiologist.\n* If diuresis \\<1,5 L while the patient is still considered volume overloaded by the treating cardiologist, the dose of bumetanide is doubled.\n\nIn case of therapy-refractory congestion, treatment is at the discretion of the treating physician, but addition of chlorthalidone 50 mg PO is recommended by the investigators as a first-line option.', 'armGroupLabels': ['High-dose loop diuretics, no spironolactone', 'High-dose loop diuretics, upfront spironolactone']}, {'name': 'Upfront therapy with oral spironolactone', 'type': 'DRUG', 'otherNames': ['Aldactone'], 'description': 'Patients randomized to this group receive oral spironolactone (25mg) immediately after randomization and in the morning of each subsequent day unless the serum potassium level is \\>5 mmol/L.\n\nNote: Investigators and treating physicians are blinded to treatment allocation for this arm, but no matching placebo is provided, so patients are not.', 'armGroupLabels': ['Acetazolamide/low-dose loop diuretics, upfront spironolactone', 'High-dose loop diuretics, upfront spironolactone']}]}, 'contactsLocationsModule': {'locations': [{'zip': '3600', 'city': 'Genk', 'state': 'Limburg', 'country': 'Belgium', 'facility': 'Ziekenhuis Oost-Limburg', 'geoPoint': {'lat': 50.965, 'lon': 5.50082}}, {'zip': '3000', 'city': 'Leuven', 'state': 'Vlaams-Brabant', 'country': 'Belgium', 'facility': 'University Hospital Leuven', 'geoPoint': {'lat': 50.87959, 'lon': 4.70093}}], 'overallOfficials': [{'name': 'Wilfried Mullens, M.D. Ph.D.', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Ziekenhuis Oost-Limburg'}, {'name': 'Frederik H. Verbrugge, M.D. Ph.D.', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Ziekenhuis Oost-Limburg'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Hasselt University', 'class': 'OTHER'}, 'collaborators': [{'name': 'Ziekenhuis Oost-Limburg', 'class': 'OTHER'}, {'name': 'Universitaire Ziekenhuizen KU Leuven', 'class': 'OTHER'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Prof. Dr.', 'investigatorFullName': 'Wilfried Mullens, MD PhD', 'investigatorAffiliation': 'Ziekenhuis Oost-Limburg'}}}}