Ignite Creation Date:
2025-12-24 @ 6:37 PM
Ignite Modification Date:
2026-02-27 @ 10:58 PM
Study NCT ID:
NCT03226457
Status:
COMPLETED
Last Update Posted:
2021-06-30
First Post:
2017-07-17
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
SGLT2 Inhibition in Combination With Diuretics in Heart Failure
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24', 'submissionTracking': {'firstMcpInfo': {'postDateStruct': {'date': '2021-05-17', 'type': 'ACTUAL'}}}}, 'conditionBrowseModule': {'meshes': [{'id': 'D006333', 'term': 'Heart Failure'}, {'id': 'D003924', 'term': 'Diabetes Mellitus, Type 2'}], 'ancestors': [{'id': 'D006331', 'term': 'Heart Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}, {'id': 'D003920', 'term': 'Diabetes Mellitus'}, {'id': 'D044882', 'term': 'Glucose Metabolism Disorders'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}, {'id': 'D004700', 'term': 'Endocrine System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C570240', 'term': 'empagliflozin'}, {'id': 'D005665', 'term': 'Furosemide'}], 'ancestors': [{'id': 'D013424', 'term': 'Sulfanilamides'}, {'id': 'D013449', 'term': 'Sulfonamides'}, {'id': 'D000577', 'term': 'Amides'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D000814', 'term': 'Aniline Compounds'}, {'id': 'D000588', 'term': 'Amines'}, {'id': 'D013450', 'term': 'Sulfones'}, {'id': 'D013457', 'term': 'Sulfur Compounds'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'n.a.mordi@dundee.ac.uk', 'phone': '+ 44 (0) 1382 383 667', 'title': 'Dr Natalie Mordi (Principle Investigator)', 'organization': 'University of Dundee'}, 'certainAgreement': {'piSponsorEmployee': True}, 'limitationsAndCaveats': {'description': 'Small, single-center crossover study. The dose investigated was 25mg empagliflozin, whereas in routine practice 10mg dose is most commonly used. We did not measure urine glucose in this study. Patients were only observed for 2 hours after administration of investigational medical. Any significant diuretic or natriuretic effect beyond this may have not been observed during this short time frame.'}}, 'adverseEventsModule': {'timeFrame': 'For the duration of the participants inclusion in the study to the point of completion e.g. 14 to 16 weeks in the trial, with a further review at 4 weeks following discontinuation of the investigational medicinal product e.g. 18 to 20 weeks in total.', 'description': 'Because of the large volume of multicenter studies reporting on the safety and adverse events of SGLT2 inhibitors, for this trial the focus was on the effects on the coprescription with loop diuretic. Adverse event data were also collected.\n\nAs a crossover study, the adverse event reporting is separated into the events that occurred on the specific intervention/treatment arms.', 'eventGroups': [{'id': 'EG000', 'title': 'Empagliflozin', 'description': "Empagliflozin (SGLT2 inhibitor) 25mg capsules once daily for 6 weeks\n\nEmpagliflozin 25mg: Empagliflozin (SGLT2 inhibitor) 25 mg once daily for 6 weeks\n\nFrusemide: Renal Physiology Test (RPT) days will be performed at week 1 and week 6 on each arm of this crossover trial. On these RPT days participants will undergo oral water loading (15mls/kg) and frequent urination at 30 minute intervals to gain a steady state diuresis. At a set time point, an intravenous bolus of furosemide at a dose of half the participant's usual loop diuretic dose will be administered.", 'otherNumAtRisk': 23, 'deathsNumAtRisk': 23, 'otherNumAffected': 1, 'seriousNumAtRisk': 23, 'deathsNumAffected': 0, 'seriousNumAffected': 2}, {'id': 'EG001', 'title': 'Placebo', 'description': "Capsules containing microcrystalline cellulose Ph Eur over encapsulated in a hard gelatine capsule shell to match the active comparator\n\nPlacebo oral capsule: Capsules containing microcrystalline cellulose Ph Eur over encapsulated in a hard gelatine capsule shell to match the active comparator once daily for 6 weeks\n\nFrusemide: Renal Physiology Test (RPT) days will be performed at week 1 and week 6 on each arm of this crossover trial. On these RPT days participants will undergo oral water loading (15mls/kg) and frequent urination at 30 minute intervals to gain a steady state diuresis. At a set time point, an intravenous bolus of furosemide at a dose of half the participant's usual loop diuretic dose will be administered.", 'otherNumAtRisk': 23, 'deathsNumAtRisk': 23, 'otherNumAffected': 2, 'seriousNumAtRisk': 23, 'deathsNumAffected': 0, 'seriousNumAffected': 0}], 'otherEvents': [{'term': 'Gout', 'notes': 'Gout', 'stats': [{'groupId': 'EG000', 'numAtRisk': 23, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 23, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 21.1'}], 'seriousEvents': [{'term': 'Hospitalization with heart failure following discontinuation of investigational medicinal product', 'stats': [{'groupId': 'EG000', 'numAtRisk': 23, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 23, 'numAffected': 0}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 21.1'}, {'term': 'Hypotension', 'stats': [{'groupId': 'EG000', 'numAtRisk': 23, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 23, 'numAffected': 0}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 21.1'}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'The Effect of Empagliflozin Versus Placebo on the Change in Urine Output.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '23', 'groupId': 'OG000'}, {'value': '23', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Empagliflozin', 'description': "Empagliflozin (SGLT2 inhibitor) 25mg capsules once daily for 6 weeks\n\nEmpagliflozin 25mg: Empagliflozin (SGLT2 inhibitor) 25 mg once daily for 6 weeks\n\nFrusemide: Renal Physiology Test (RPT) days will be performed at week 1 and week 6 on each arm of this crossover trial. On these RPT days participants will undergo oral water loading (15mls/kg) and frequent urination at 30 minute intervals to gain a steady state diuresis. At a set time point, an intravenous bolus of furosemide at a dose of half the participant's usual loop diuretic dose will be administered."}, {'id': 'OG001', 'title': 'Placebo', 'description': "Capsules containing microcrystalline cellulose Ph Eur over encapsulated in a hard gelatine capsule shell to match the active comparator\n\nPlacebo oral capsule: Capsules containing microcrystalline cellulose Ph Eur over encapsulated in a hard gelatine capsule shell to match the active comparator once daily for 6 weeks\n\nFrusemide: Renal Physiology Test (RPT) days will be performed at week 1 and week 6 on each arm of this crossover trial. On these RPT days participants will undergo oral water loading (15mls/kg) and frequent urination at 30 minute intervals to gain a steady state diuresis. At a set time point, an intravenous bolus of furosemide at a dose of half the participant's usual loop diuretic dose will be administered."}], 'classes': [{'categories': [{'measurements': [{'value': '545', 'groupId': 'OG000', 'lowerLimit': '136', 'upperLimit': '954'}, {'value': '-113', 'groupId': 'OG001', 'lowerLimit': '-345', 'upperLimit': '119'}]}]}], 'analyses': [{'pValue': '= 0.005', 'groupIds': ['OG000', 'OG001'], 'pValueComment': '(calculated)', 'groupDescription': 'Details on the statistical analysis are published in the Circulation, DOI: 10.1161/CIRCULATIONAHA.120.048739\n\nAnalyses were performed on the primary and secondary measures comparing empagliflozin versus placebo and assessed by 2-way analysis of covariance correcting for treatment order, baseline value, and any percentage change in furosemide dose at the visit. Data for continuous outcome measures were assessed for normality before analysis.', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'Details of the power calculation are published in the Circulation, DOI: 10.1161/CIRCULATIONAHA.120.048739'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Change from baseline to 6 weeks', 'description': 'Change from urinary volume from baseline (mls).', 'unitOfMeasure': 'mL', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'The Effect of Empagliflozin Versus Placebo on the Change in Urinary Sodium Excretion.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '23', 'groupId': 'OG000'}, {'value': '23', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Empagliflozin', 'description': "Empagliflozin (SGLT2 inhibitor) 25mg capsules once daily for 6 weeks\n\nEmpagliflozin 25mg: Empagliflozin (SGLT2 inhibitor) 25 mg once daily for 6 weeks\n\nFrusemide: Renal Physiology Test (RPT) days will be performed at week 1 and week 6 on each arm of this crossover trial. On these RPT days participants will undergo oral water loading (15mls/kg) and frequent urination at 30 minute intervals to gain a steady state diuresis. At a set time point, an intravenous bolus of furosemide at a dose of half the participant's usual loop diuretic dose will be administered."}, {'id': 'OG001', 'title': 'Placebo', 'description': "Capsules containing microcrystalline cellulose Ph Eur over encapsulated in a hard gelatine capsule shell to match the active comparator\n\nPlacebo oral capsule: Capsules containing microcrystalline cellulose Ph Eur over encapsulated in a hard gelatine capsule shell to match the active comparator once daily for 6 weeks\n\nFrusemide: Renal Physiology Test (RPT) days will be performed at week 1 and week 6 on each arm of this crossover trial. On these RPT days participants will undergo oral water loading (15mls/kg) and frequent urination at 30 minute intervals to gain a steady state diuresis. At a set time point, an intravenous bolus of furosemide at a dose of half the participant's usual loop diuretic dose will be administered."}], 'classes': [{'categories': [{'measurements': [{'value': '0.11', 'groupId': 'OG000', 'lowerLimit': '-0.22', 'upperLimit': '0.44'}, {'value': '-0.00', 'groupId': 'OG001', 'lowerLimit': '-0.19', 'upperLimit': '0.19'}]}]}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Change from baseline to 6 weeks', 'description': 'The effect of empagliflozin versus placebo on the change in urinary sodium excretion: change in fractional urinary sodium excretion from baseline (%).', 'unitOfMeasure': 'percentage of change in FENa', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Number of Participants With a Change in CKD Category as Dictated by the Glomerular Filtration Rate', 'denoms': [{'units': 'Participants', 'counts': [{'value': '23', 'groupId': 'OG000'}, {'value': '23', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Empagliflozin', 'description': "Empagliflozin (SGLT2 inhibitor) 25mg capsules once daily for 6 weeks\n\nEmpagliflozin 25mg: Empagliflozin (SGLT2 inhibitor) 25 mg once daily for 6 weeks\n\nFrusemide: Renal Physiology Test (RPT) days will be performed at week 1 and week 6 on each arm of this crossover trial. On these RPT days participants will undergo oral water loading (15mls/kg) and frequent urination at 30 minute intervals to gain a steady state diuresis. At a set time point, an intravenous bolus of furosemide at a dose of half the participant's usual loop diuretic dose will be administered."}, {'id': 'OG001', 'title': 'Placebo', 'description': "Capsules containing microcrystalline cellulose Ph Eur over encapsulated in a hard gelatine capsule shell to match the active comparator\n\nPlacebo oral capsule: Capsules containing microcrystalline cellulose Ph Eur over encapsulated in a hard gelatine capsule shell to match the active comparator once daily for 6 weeks\n\nFrusemide: Renal Physiology Test (RPT) days will be performed at week 1 and week 6 on each arm of this crossover trial. On these RPT days participants will undergo oral water loading (15mls/kg) and frequent urination at 30 minute intervals to gain a steady state diuresis. At a set time point, an intravenous bolus of furosemide at a dose of half the participant's usual loop diuretic dose will be administered."}], 'classes': [{'categories': [{'measurements': [{'value': '6', 'groupId': 'OG000'}, {'value': '5', 'groupId': 'OG001'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'From baseline to 6 weeks', 'description': 'The effect of empagliflozin versus placebo on the change in glomerular filtration rate: Change in estimated glomerular filtration rate from baseline (ml/min/1.73m2).\n\nData was recorded as a persistent reduction in CKD category in the empagliflozin group versus placebo', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'The Effect of Empagliflozin Versus Placebo on the Change in Serum Creatinine.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '23', 'groupId': 'OG000'}, {'value': '23', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Empagliflozin', 'description': "Empagliflozin (SGLT2 inhibitor) 25mg capsules once daily for 6 weeks\n\nEmpagliflozin 25mg: Empagliflozin (SGLT2 inhibitor) 25 mg once daily for 6 weeks\n\nFrusemide: Renal Physiology Test (RPT) days will be performed at week 1 and week 6 on each arm of this crossover trial. On these RPT days participants will undergo oral water loading (15mls/kg) and frequent urination at 30 minute intervals to gain a steady state diuresis. At a set time point, an intravenous bolus of furosemide at a dose of half the participant's usual loop diuretic dose will be administered."}, {'id': 'OG001', 'title': 'Placebo', 'description': "Capsules containing microcrystalline cellulose Ph Eur over encapsulated in a hard gelatine capsule shell to match the active comparator\n\nPlacebo oral capsule: Capsules containing microcrystalline cellulose Ph Eur over encapsulated in a hard gelatine capsule shell to match the active comparator once daily for 6 weeks\n\nFrusemide: Renal Physiology Test (RPT) days will be performed at week 1 and week 6 on each arm of this crossover trial. On these RPT days participants will undergo oral water loading (15mls/kg) and frequent urination at 30 minute intervals to gain a steady state diuresis. At a set time point, an intravenous bolus of furosemide at a dose of half the participant's usual loop diuretic dose will be administered."}], 'classes': [{'categories': [{'measurements': [{'value': '-0.44', 'groupId': 'OG000', 'lowerLimit': '-8.82', 'upperLimit': '7.94'}, {'value': '-10.81', 'groupId': 'OG001', 'lowerLimit': '-19.2', 'upperLimit': '-2.44'}]}]}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Change from baseline to 6 weeks', 'description': 'Change in serum creatinine from baseline (mmol/L).', 'unitOfMeasure': 'mmol/L', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'The Effect of Empagliflozin Versus Placebo on the Change to Urinary Protein/Creatinine Ratio.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '12', 'groupId': 'OG000'}, {'value': '11', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Empagliflozin', 'description': "Empagliflozin (SGLT2 inhibitor) 25mg capsules once daily for 6 weeks\n\nEmpagliflozin 25mg: Empagliflozin (SGLT2 inhibitor) 25 mg once daily for 6 weeks\n\nFrusemide: Renal Physiology Test (RPT) days will be performed at week 1 and week 6 on each arm of this crossover trial. On these RPT days participants will undergo oral water loading (15mls/kg) and frequent urination at 30 minute intervals to gain a steady state diuresis. At a set time point, an intravenous bolus of furosemide at a dose of half the participant's usual loop diuretic dose will be administered."}, {'id': 'OG001', 'title': 'Placebo', 'description': "Capsules containing microcrystalline cellulose Ph Eur over encapsulated in a hard gelatine capsule shell to match the active comparator\n\nPlacebo oral capsule: Capsules containing microcrystalline cellulose Ph Eur over encapsulated in a hard gelatine capsule shell to match the active comparator once daily for 6 weeks\n\nFrusemide: Renal Physiology Test (RPT) days will be performed at week 1 and week 6 on each arm of this crossover trial. On these RPT days participants will undergo oral water loading (15mls/kg) and frequent urination at 30 minute intervals to gain a steady state diuresis. At a set time point, an intravenous bolus of furosemide at a dose of half the participant's usual loop diuretic dose will be administered."}], 'classes': [{'categories': [{'measurements': [{'value': '2.26', 'groupId': 'OG000', 'lowerLimit': '-1.75', 'upperLimit': '6.28'}, {'value': '-3.05', 'groupId': 'OG001', 'lowerLimit': '-7.05', 'upperLimit': '0.97'}]}]}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Change from baseline to 6 weeks', 'description': 'The effect of empagliflozin versus placebo on the change to urinary protein/creatinine ratio: Change in urinary protein/creatinine ratio from baseline (mg/mmol).', 'unitOfMeasure': 'mg/mmol', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'The Effect of Empagliflozin Versus Placebo on the Change to Urinary Albumin/Creatinine Ratio.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '23', 'groupId': 'OG000'}, {'value': '23', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Empagliflozin', 'description': "Empagliflozin (SGLT2 inhibitor) 25mg capsules once daily for 6 weeks\n\nEmpagliflozin 25mg: Empagliflozin (SGLT2 inhibitor) 25 mg once daily for 6 weeks\n\nFrusemide: Renal Physiology Test (RPT) days will be performed at week 1 and week 6 on each arm of this crossover trial. On these RPT days participants will undergo oral water loading (15mls/kg) and frequent urination at 30 minute intervals to gain a steady state diuresis. At a set time point, an intravenous bolus of furosemide at a dose of half the participant's usual loop diuretic dose will be administered."}, {'id': 'OG001', 'title': 'Placebo', 'description': "Capsules containing microcrystalline cellulose Ph Eur over encapsulated in a hard gelatine capsule shell to match the active comparator\n\nPlacebo oral capsule: Capsules containing microcrystalline cellulose Ph Eur over encapsulated in a hard gelatine capsule shell to match the active comparator once daily for 6 weeks\n\nFrusemide: Renal Physiology Test (RPT) days will be performed at week 1 and week 6 on each arm of this crossover trial. On these RPT days participants will undergo oral water loading (15mls/kg) and frequent urination at 30 minute intervals to gain a steady state diuresis. At a set time point, an intravenous bolus of furosemide at a dose of half the participant's usual loop diuretic dose will be administered."}], 'classes': [{'categories': [{'measurements': [{'value': '1.18', 'groupId': 'OG000', 'lowerLimit': '-0.69', 'upperLimit': '3.05'}, {'value': '-1.1', 'groupId': 'OG001', 'lowerLimit': '-2.98', 'upperLimit': '0.77'}]}]}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Change from baseline to 6 weeks', 'description': 'The effect of empagliflozin versus placebo on the change to urinary albumin/creatinine ratio: Change in urinary albumin/creatinine ratio from baseline (mg/mmol).', 'unitOfMeasure': 'mg/mmol', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'The Effect of Empagliflozin Versus Placebo on the Change to the Renal Biomarker, Cystatin C.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '23', 'groupId': 'OG000'}, {'value': '23', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Empagliflozin', 'description': "Empagliflozin (SGLT2 inhibitor) 25mg capsules once daily for 6 weeks\n\nEmpagliflozin 25mg: Empagliflozin (SGLT2 inhibitor) 25 mg once daily for 6 weeks\n\nFrusemide: Renal Physiology Test (RPT) days will be performed at week 1 and week 6 on each arm of this crossover trial. On these RPT days participants will undergo oral water loading (15mls/kg) and frequent urination at 30 minute intervals to gain a steady state diuresis. At a set time point, an intravenous bolus of furosemide at a dose of half the participant's usual loop diuretic dose will be administered."}, {'id': 'OG001', 'title': 'Placebo', 'description': "Capsules containing microcrystalline cellulose Ph Eur over encapsulated in a hard gelatine capsule shell to match the active comparator\n\nPlacebo oral capsule: Capsules containing microcrystalline cellulose Ph Eur over encapsulated in a hard gelatine capsule shell to match the active comparator once daily for 6 weeks\n\nFrusemide: Renal Physiology Test (RPT) days will be performed at week 1 and week 6 on each arm of this crossover trial. On these RPT days participants will undergo oral water loading (15mls/kg) and frequent urination at 30 minute intervals to gain a steady state diuresis. At a set time point, an intravenous bolus of furosemide at a dose of half the participant's usual loop diuretic dose will be administered."}], 'classes': [{'categories': [{'measurements': [{'value': '31.35', 'groupId': 'OG000', 'lowerLimit': '-80.07', 'upperLimit': '142.75'}, {'value': '22.5', 'groupId': 'OG001', 'lowerLimit': '-91.52', 'upperLimit': '136.52'}]}]}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Change from baseline to 6 weeks', 'description': 'The effect of empagliflozin versus placebo on the change to the renal biomarker, cystatin C: Change in Cystatin C from baseline (ng/ml).', 'unitOfMeasure': 'ng/ml', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Empagliflozin/Placebo', 'description': "Treatment Sequence:\n\nEmpagliflozin (SGLT2 inhibitor) 25mg capsules once daily for 6 weeks\n\nEmpagliflozin 25mg: Empagliflozin (SGLT2 inhibitor) 25 mg once daily for 6 weeks\n\nFrusemide: Renal Physiology Test (RPT) days will be performed at week 1 and week 6 on each arm of this crossover trial. On these RPT days participants will undergo oral water loading (15mls/kg) and frequent urination at 30 minute intervals to gain a steady state diuresis. At a set time point, an intravenous bolus of furosemide at a dose of half the participant's usual loop diuretic dose will be administered.\n\nMinimum of a 2 week washout period.\n\n6 weeks of placebo"}, {'id': 'FG001', 'title': 'Placebo/Empagliflozin', 'description': "Treatment Sequence:\n\nCapsules containing microcrystalline cellulose Ph Eur over encapsulated in a hard gelatine capsule shell to match the active comparator\n\nPlacebo oral capsule: Capsules containing microcrystalline cellulose Ph Eur over encapsulated in a hard gelatine capsule shell to match the active comparator once daily for 6 weeks\n\nFrusemide: Renal Physiology Test (RPT) days will be performed at week 1 and week 6 on each arm of this crossover trial. On these RPT days participants will undergo oral water loading (15mls/kg) and frequent urination at 30 minute intervals to gain a steady state diuresis. At a set time point, an intravenous bolus of furosemide at a dose of half the participant's usual loop diuretic dose will be administered.\n\nMinimum of 2 week washout period\n\n6 weeks of Empagliflozin 25mg: Empagliflozin (SGLT2 inhibitor) 25 mg once daily"}], 'periods': [{'title': 'Treatment 1: 6 Weeks', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '12'}, {'groupId': 'FG001', 'numSubjects': '11'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '12'}, {'groupId': 'FG001', 'numSubjects': '11'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}, {'title': 'Washout Period: Minimum 2 Weeks', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '12'}, {'groupId': 'FG001', 'numSubjects': '11'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '12'}, {'groupId': 'FG001', 'numSubjects': '11'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}, {'title': 'Treatment 2: 6 Weeks', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '12'}, {'groupId': 'FG001', 'numSubjects': '11'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '12'}, {'groupId': 'FG001', 'numSubjects': '11'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '23', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'Baseline Characteristics', 'description': 'N = 23, Crossover study design. Baseline characteristics'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'categories': [{'title': '<=18 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '5', 'groupId': 'BG000'}]}, {'title': '>=65 years', 'measurements': [{'value': '18', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '69.8', 'spread': '5.7', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '6', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '17', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Asian', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Black or African American', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'White', 'measurements': [{'value': '23', 'groupId': 'BG000'}]}, {'title': 'More than one race', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United Kingdom', 'categories': [{'measurements': [{'value': '23', 'groupId': 'BG000'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2018-01-22', 'size': 726494, 'label': 'Study Protocol', 'hasIcf': False, 'hasSap': False, 'filename': 'Prot_000.pdf', 'typeAbbrev': 'Prot', 'uploadDate': '2021-04-22T18:10', 'hasProtocol': True}, {'date': '2018-11-01', 'size': 305748, 'label': 'Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'SAP_001.pdf', 'typeAbbrev': 'SAP', 'uploadDate': '2021-04-22T17:53', 'hasProtocol': False}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR'], 'maskingDescription': 'Double-Blind'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'CROSSOVER', 'interventionModelDescription': '6 week period of Investigational Medicinal Product (Empagliflozin 25 mg od) or placebo. A 2 week washout period will then be observed, followed by the second arm with a further 6 week period of placebo or IMP. At week 1 and week 6 of each arm, detailed Renal Physiology Test days will be performed.'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 23}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2017-12-11', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2021-06', 'dispFirstSubmitDate': '2019-07-08', 'completionDateStruct': {'date': '2019-01-09', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2021-06-22', 'studyFirstSubmitDate': '2017-07-17', 'dispFirstSubmitQcDate': '2021-06-22', 'resultsFirstSubmitDate': '2021-04-23', 'studyFirstSubmitQcDate': '2017-07-20', 'dispFirstPostDateStruct': {'date': '2021-06-30', 'type': 'ACTUAL'}, 'lastUpdatePostDateStruct': {'date': '2021-06-30', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2021-06-22', 'studyFirstPostDateStruct': {'date': '2017-07-21', 'type': 'ACTUAL'}, 'resultsFirstPostDateStruct': {'date': '2021-06-30', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2018-12-11', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'The Effect of Empagliflozin Versus Placebo on the Change in Urine Output.', 'timeFrame': 'Change from baseline to 6 weeks', 'description': 'Change from urinary volume from baseline (mls).'}], 'secondaryOutcomes': [{'measure': 'The Effect of Empagliflozin Versus Placebo on the Change in Urinary Sodium Excretion.', 'timeFrame': 'Change from baseline to 6 weeks', 'description': 'The effect of empagliflozin versus placebo on the change in urinary sodium excretion: change in fractional urinary sodium excretion from baseline (%).'}, {'measure': 'Number of Participants With a Change in CKD Category as Dictated by the Glomerular Filtration Rate', 'timeFrame': 'From baseline to 6 weeks', 'description': 'The effect of empagliflozin versus placebo on the change in glomerular filtration rate: Change in estimated glomerular filtration rate from baseline (ml/min/1.73m2).\n\nData was recorded as a persistent reduction in CKD category in the empagliflozin group versus placebo'}, {'measure': 'The Effect of Empagliflozin Versus Placebo on the Change in Serum Creatinine.', 'timeFrame': 'Change from baseline to 6 weeks', 'description': 'Change in serum creatinine from baseline (mmol/L).'}, {'measure': 'The Effect of Empagliflozin Versus Placebo on the Change to Urinary Protein/Creatinine Ratio.', 'timeFrame': 'Change from baseline to 6 weeks', 'description': 'The effect of empagliflozin versus placebo on the change to urinary protein/creatinine ratio: Change in urinary protein/creatinine ratio from baseline (mg/mmol).'}, {'measure': 'The Effect of Empagliflozin Versus Placebo on the Change to Urinary Albumin/Creatinine Ratio.', 'timeFrame': 'Change from baseline to 6 weeks', 'description': 'The effect of empagliflozin versus placebo on the change to urinary albumin/creatinine ratio: Change in urinary albumin/creatinine ratio from baseline (mg/mmol).'}, {'measure': 'The Effect of Empagliflozin Versus Placebo on the Change to the Renal Biomarker, Cystatin C.', 'timeFrame': 'Change from baseline to 6 weeks', 'description': 'The effect of empagliflozin versus placebo on the change to the renal biomarker, cystatin C: Change in Cystatin C from baseline (ng/ml).'}]}, 'oversightModule': {'isUsExport': True, 'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Heart Failure', 'Type 2 Diabetes Mellitus', 'Sodium-Glucose co-Transporter 2 (SGLT2) inhibitors', 'Natriuresis', 'Diuresis'], 'conditions': ['Heart Failure', 'Type 2 Diabetes Mellitus']}, 'referencesModule': {'references': [{'pmid': '32865004', 'type': 'DERIVED', 'citation': 'Mordi NA, Mordi IR, Singh JS, McCrimmon RJ, Struthers AD, Lang CC. Renal and Cardiovascular Effects of SGLT2 Inhibition in Combination With Loop Diuretics in Patients With Type 2 Diabetes and Chronic Heart Failure: The RECEDE-CHF Trial. Circulation. 2020 Nov 3;142(18):1713-1724. doi: 10.1161/CIRCULATIONAHA.120.048739. Epub 2020 Aug 29.'}, {'pmid': '29042392', 'type': 'DERIVED', 'citation': 'Mordi NA, Mordi IR, Singh JS, Baig F, Choy AM, McCrimmon RJ, Struthers AD, Lang CC. Renal and Cardiovascular Effects of sodium-glucose cotransporter 2 (SGLT2) inhibition in combination with loop Diuretics in diabetic patients with Chronic Heart Failure (RECEDE-CHF): protocol for a randomised controlled double-blind cross-over trial. BMJ Open. 2017 Oct 16;7(10):e018097. doi: 10.1136/bmjopen-2017-018097.'}]}, 'descriptionModule': {'briefSummary': 'The RECEDE-CHF trial is a single centre phase IV, randomised, double-blind, placebo-controlled, crossover trial conducted in NHS Tayside, Scotland comparing empagliflozin 25mg, to placebo in patients with Type 2 Diabetes and mild Chronic Heart Failure with left ventricular systolic dysfunction who are already on a loop diuretic. Renal physiological testing will be performed at two points on each arm to assess the effect of empagliflozin, on urinary volume, compared to placebo. The secondary outcomes are to assess the effect of empagliflozin in addition to loop diuretics on natriuresis, to assess the safety of add-on SGLT2 inhibitor therapy as measured by changes to serum creatinine and eGFR, to assess effects of empagliflozin on urinary protein/creatinine ratio, albumin/creatinine ratio and cystatin C when compared to placebo.', 'detailedDescription': "Type 2 Diabetes (T2D) and Heart Failure (HF) are a frequent combination, where treatment options remain limited. There has been increasing interest around the sodium-glucose co-transporter 2 (SGLT2) inhibitors and their use in patients with HF. This is following publication of EMPA-REG OUTCOME trial that reported a 14% reduction in the primary composite outcome of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and \\>30% reductions in cardiovascular mortality, overall mortality and HF hospitalisations in patients randomised to the SGLT2 inhibitor, empagliflozin, when compared to placebo. Data on the effect of SGLT2 inhibitor use with diuretics is limited. We hypothesize that, in the diabetic CHF population, SGLT2 inhibition may augment the effects of loop diuretics.\n\nRenal Physiology Test (RPT) days will be performed at week 1 and week 6 on each arm of this crossover trial. On these RPT days participants will undergo oral water loading (15mls/kg) and frequent urination at 30 minute intervals to gain a steady state diuresis. The investigational medicinal product will be administered, followed by an intravenous bolus of furosemide at a dose of half the participant's usual loop diuretic dose.\n\nThis proof of concept trial will aim to shed light on the mechanism of the cardiovascular and renal outcomes demonstrated in the recent EMPA-REG study by documenting the influence of the SGLT2 inhibitors when used in combination with a loop diuretic on diuresis and natriuresis when compared to placebo.\n\nThe RECEDE-CHF trial is funded by the British Heart Foundation (BHF grant number: 807998). NAM is a BHF funded clinical research fellow."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '80 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Diagnosis of NYHA Functional class II-III HF with prior echocardiographic evidence of LVSD.\n* On stable doses of furosemide, or alternative loop diuretic for at least one month.\n* Stable Type 2 Diabetes (HbA1c, in the last 3 months, of 6.5% ≤ and ≤10.0%)\n* eGFR ≥ 45 ml/min.\n* Have stable HF symptoms for at least three months prior to consent\n* On stable HF therapy for at least three months prior to consent\n* Have not been hospitalised for HF for at least three months prior to consent.\n* Women of childbearing potential must agree to take precautions to avoid pregnancy throughout the trial and for 4 weeks after intake of the last dose.\n\nExclusion Criteria:\n\n* A diagnosis of chronic liver disease and/or liver enzymes that are twice the upper limit of normal\n* Systolic BP of \\<95mmHg at screening visit.\n* Participants on thiazide diuretics.\n* Participants receiving renal dialysis\n* Participants who have previously had an episode of diabetic ketoacidosis.\n* Participants with type 1 diabetes mellitus\n* Malignancy (receiving active treatment) or other life threatening disease.\n* Pregnant or lactating women\n* Participants with difficulty in micturition e.g. severe prostate enlargement\n* Allergy to any SGLT2 inhibitor or lactose or galactose intolerance\n* Past or current treatment with any SGLT2 inhibitor\n* Participants who have participated in any other clinical interventional trial of an investigational medicinal product within 30 days.\n* Participants who are unable to give informed consent\n* Any other reason considered by the physician to be inappropriate for inclusion.'}, 'identificationModule': {'nctId': 'NCT03226457', 'acronym': 'RECEDE-CHF', 'briefTitle': 'SGLT2 Inhibition in Combination With Diuretics in Heart Failure', 'organization': {'class': 'OTHER', 'fullName': 'University of Dundee'}, 'officialTitle': 'Renal and Cardiovascular Effect of Sodium-Glucose Co-Transporter 2 (SGLT2) Inhibition in Combination With Loop Diuretics in Diabetic Patients With Chronic Heart Failure', 'orgStudyIdInfo': {'id': 'BHF:807998'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Empagliflozin/Placebo', 'description': 'Empagliflozin (SGLT2 inhibitor) 25mg capsules once daily for 6 weeks, minimum of a 2 week washout period, then 6 weeks placebo', 'interventionNames': ['Drug: Empagliflozin 25mg', 'Drug: Placebo oral capsule', 'Drug: Frusemide']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Placebo/Empagliflozin', 'description': 'Placebo for 6 weeks, minimum of a 2 week washout period, followed by Empagliflozin (SGLT2 inhibitor) 25mg capsules once daily for 6 weeks', 'interventionNames': ['Drug: Empagliflozin 25mg', 'Drug: Placebo oral capsule', 'Drug: Frusemide']}], 'interventions': [{'name': 'Empagliflozin 25mg', 'type': 'DRUG', 'otherNames': ['Jardiance'], 'description': 'Empagliflozin (SGLT2 inhibitor) 25 mg once daily for 6 weeks', 'armGroupLabels': ['Empagliflozin/Placebo', 'Placebo/Empagliflozin']}, {'name': 'Placebo oral capsule', 'type': 'DRUG', 'otherNames': ['Placebo'], 'description': 'Capsules containing microcrystalline cellulose Ph Eur over encapsulated in a hard gelatine capsule shell to match the active comparator once daily for 6 weeks', 'armGroupLabels': ['Empagliflozin/Placebo', 'Placebo/Empagliflozin']}, {'name': 'Frusemide', 'type': 'DRUG', 'description': "Renal Physiology Test (RPT) days will be performed at week 1 and week 6 on each arm of this crossover trial. On these RPT days participants will undergo oral water loading (15mls/kg) and frequent urination at 30 minute intervals to gain a steady state diuresis. At a set time point, an intravenous bolus of furosemide at a dose of half the participant's usual loop diuretic dose will be administered.", 'armGroupLabels': ['Empagliflozin/Placebo', 'Placebo/Empagliflozin']}]}, 'contactsLocationsModule': {'locations': [{'zip': 'DD1 9SY', 'city': 'Dundee', 'state': 'Angus', 'country': 'United Kingdom', 'facility': 'University of Dundee, Ninewells Hospital and Medical School', 'geoPoint': {'lat': 56.46913, 'lon': -2.97489}}], 'overallOfficials': [{'name': 'Natalie A Mordi, MBChB MRCP', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of Dundee'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Dundee', 'class': 'OTHER'}, 'collaborators': [{'name': 'British Heart Foundation', 'class': 'OTHER'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'British Heart Foundation Clinical Research Fellow', 'investigatorFullName': 'Natalie Mordi', 'investigatorAffiliation': 'University of Dundee'}}}}