Ignite Creation Date:
2025-12-24 @ 2:35 PM
Ignite Modification Date:
2026-01-04 @ 4:49 PM
Study NCT ID:
NCT05753059
Status:
RECRUITING
Last Update Posted:
2025-06-18
First Post:
2023-02-21
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Mechanisms of Diuretic Resistance in Heart Failure, Aim 2
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D006333', 'term': 'Heart Failure'}], 'ancestors': [{'id': 'D006331', 'term': 'Heart Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000584', 'term': 'Amiloride'}, {'id': 'D001539', 'term': 'Bendroflumethiazide'}], 'ancestors': [{'id': 'D011719', 'term': 'Pyrazines'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D001581', 'term': 'Benzothiadiazines'}, {'id': 'D013449', 'term': 'Sulfonamides'}, {'id': 'D013450', 'term': 'Sulfones'}, {'id': 'D013457', 'term': 'Sulfur Compounds'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D049971', 'term': 'Thiazides'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR']}, 'primaryPurpose': 'OTHER', 'interventionModel': 'CROSSOVER', 'interventionModelDescription': 'Randomized placebo-controlled, double-blind, double-dummy, crossover design'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 50}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2023-08-10', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-06', 'completionDateStruct': {'date': '2027-06', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-06-13', 'studyFirstSubmitDate': '2023-02-21', 'studyFirstSubmitQcDate': '2023-02-21', 'lastUpdatePostDateStruct': {'date': '2025-06-18', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2023-03-03', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2027-06', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Change in peak FENa from bumetanide monotherapy to bumetanide plus combination therapy', 'timeFrame': '21 days', 'description': 'Change in peak FENa from bumetanide monotherapy to bumetanide plus combination therapy'}, {'measure': 'Change in distal sodium reabsorption', 'timeFrame': '21 days', 'description': 'Change in distal sodium reabsorption (FELi minus FENa) from bumetanide monotherapy to bumetanide plus combination therapy'}, {'measure': 'Correlation between distal sodium reabsorption and uEV pendrin/CD9', 'timeFrame': '21 days', 'description': 'Correlation between distal sodium reabsorption (FELi minus FENa) and uEV pendrin/CD9'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Heart Failure']}, 'descriptionModule': {'briefSummary': 'Randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations placebo/placebo, bendroflumethiazide/placebo, amiloride/placebo, and bendroflumethiazide/amiloride added to bumetanide.', 'detailedDescription': 'This study will employ a randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations placebo/placebo, bendroflumethiazide/placebo, amiloride/placebo, and bendroflumethiazide/amiloride added to bumetanide.\n\nPatients will be co-enrolled in this study and an ancillary study for administration of Bendroflumethiazide. Administration of bendroflumethiazide will take place under an ancillary protocol.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Clinical diagnosis of HF\n2. No plan for titration/change of heart failure medical or device therapies during the study period.\n3. Absence of non-elective hospitalizations in the previous 2 weeks\n4. At optimal volume status by symptoms, exam, and dry weight.\n5. Serum potassium ≤ 5.0 mmol/L\n6. Serum sodium ≥ 130 mEq/L\n7. Age \\> 18 years\n8. Hemoglobin ≥8 g/dL\n9. Objective evidence of diuretic resistance to a 10mg bumetanide challenge, defined as:\n\n 1. FENa \\<10% and total sodium output \\<150mmol and\n 2. At least one of the following criteria:\n\n1\\. Chronic home furosemide dose \\> or equal to 80mg furosemide equivalents daily 2. eGFR \\< 60ml/min 3. Serum chloride \\<100mmol/L 4. FENa \\<5% and total sodium output \\<75mmol on the 2 hour screening\n\nExclusion Criteria:\n\n1. GFR \\<20 ml/min/1.73m2 using the CKD-EPI equation or use of renal replacement therapies\n2. Use of any non-loop type diuretic in the last 7 days or 5 half lives, with the exclusion of low dose aldosterone antagonist (e.g., spironolactone or eplerenone ≤50 mg). Examples of non-loop diuretics include but may not be limited to acetazolamide (oral or IV, not ophthalmic), metolazone, HCTZ, chlorthalidone, chlorothiazide, indapamide, triamterene, amiloride, finerenone, spironolactone dose \\> 50mg day, eplerenone \\> 50mg/day,\n3. History of flash pulmonary edema requiring hospitalization and treatment with biphasic positive airway pressure or mechanical ventilation or a "brittle" volume sensitive HF phenotype such as an infiltrative or restrictive cardiomyopathy (i.e. amyloid cardiomyopathy, etc).\n4. Hemoglobin \\< 8 g/dL or symptomatic anemia\n5. Pregnant or breastfeeding\n6. Inability to give written informed consent or comply with study protocol or follow-up visits\n7. Chronic urinary retention limiting ability to perform timed urine collection procedures\n8. On Lithium therapy\n9. On pimozide or thioridazine\n10. Diagnosis of liver failure\n11. Contraindications or allergy to sulfonamides\n12. Any contraindication to thiazide diuretic or allergy to thiazide or bendroflumethiazide'}, 'identificationModule': {'nctId': 'NCT05753059', 'acronym': 'MsDR 2', 'briefTitle': 'Mechanisms of Diuretic Resistance in Heart Failure, Aim 2', 'organization': {'class': 'OTHER', 'fullName': 'Yale University'}, 'officialTitle': 'Mechanisms of Diuretic Resistance in Heart Failure, Aim 2', 'orgStudyIdInfo': {'id': '2000034315'}, 'secondaryIdInfos': [{'id': '1R01DK130997-01', 'link': 'https://reporter.nih.gov/quickSearch/1R01DK130997-01', 'type': 'NIH'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo/ Placebo', 'description': 'This study will employ a randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations placebo/placebo, bendroflumethiazide/placebo, amiloride/placebo, and bendroflumethiazide/amiloride added to bumetanide on Days 0, 7, 14 and 21', 'interventionNames': ['Drug: Placebo']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Placebo/ Amiloride', 'description': 'This study will employ a randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations placebo/placebo, bendroflumethiazide/placebo, amiloride/placebo, and bendroflumethiazide/amiloride added to bumetanide on Days 0, 7, 14 and 21', 'interventionNames': ['Drug: Placebo', 'Drug: Amiloride']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Placebo/ Bendroflumethiazide', 'description': 'This study will employ a randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations placebo/placebo, bendroflumethiazide/placebo, amiloride/placebo, and bendroflumethiazide/amiloride added to bumetanide on Days 0, 7, 14 and 21', 'interventionNames': ['Drug: Placebo', 'Drug: Bendroflumethiazide']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Bendroflumethiazide/ Amiloride', 'description': 'This study will employ a randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations placebo/placebo, bendroflumethiazide/placebo, amiloride/placebo, and bendroflumethiazide/amiloride added to bumetanide on Days 0, 7, 14 and 21', 'interventionNames': ['Drug: Amiloride', 'Drug: Bendroflumethiazide']}], 'interventions': [{'name': 'Placebo', 'type': 'DRUG', 'description': 'This study will employ a randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations placebo/placebo, bendroflumethiazide/placebo, amiloride/placebo, added to bumetanide on Days 0, 7, 14 and 21', 'armGroupLabels': ['Placebo/ Amiloride', 'Placebo/ Bendroflumethiazide', 'Placebo/ Placebo']}, {'name': 'Amiloride', 'type': 'DRUG', 'description': 'This study will employ a randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations of amiloride/placebo, and bendroflumethiazide/amiloride added to bumetanide on Days 0, 7, 14 and 21', 'armGroupLabels': ['Bendroflumethiazide/ Amiloride', 'Placebo/ Amiloride']}, {'name': 'Bendroflumethiazide', 'type': 'DRUG', 'description': 'This study will employ a randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations of bendroflumethiazide/placebo and bendroflumethiazide/amiloride added to bumetanide on Days 0, 7, 14 and 21', 'armGroupLabels': ['Bendroflumethiazide/ Amiloride', 'Placebo/ Bendroflumethiazide']}]}, 'contactsLocationsModule': {'locations': [{'zip': '06510', 'city': 'New Haven', 'state': 'Connecticut', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Veena Rao', 'role': 'CONTACT'}], 'facility': 'Yale University', 'geoPoint': {'lat': 41.30815, 'lon': -72.92816}}], 'centralContacts': [{'name': 'Veena Rao', 'role': 'CONTACT', 'email': 'veena.s.rao@yale.edu', 'phone': '203-737-3571'}, {'name': 'Kara Otis', 'role': 'CONTACT', 'email': 'kara.otis@yale.edu', 'phone': '203-737-3571'}], 'overallOfficials': [{'name': 'Jeffrey Testani', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Yale University'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Yale University', 'class': 'OTHER'}, 'collaborators': [{'name': 'National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)', 'class': 'NIH'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Associate Professor of Medicine', 'investigatorFullName': 'Jeffrey Testani', 'investigatorAffiliation': 'Yale University'}}}}