Mechanisms of Diuretic Resistance in Heart Failure, Aim 2
NCT ID: NCT05753059
Last Updated: 2025-06-18
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE1
50 participants
INTERVENTIONAL
2023-08-10
2027-06-30
Brief Summary
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Detailed Description
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Patients 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.
Conditions
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Study Design
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RANDOMIZED
CROSSOVER
OTHER
TRIPLE
Study Groups
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Placebo/ Amiloride
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
Placebo
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
Amiloride
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
Placebo/ Bendroflumethiazide
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
Placebo
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
Bendroflumethiazide
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
Bendroflumethiazide/ Amiloride
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
Amiloride
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
Bendroflumethiazide
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
Placebo/ Placebo
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
Placebo
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
Interventions
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Placebo
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
Amiloride
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
Bendroflumethiazide
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
Eligibility Criteria
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Inclusion Criteria
2. No plan for titration/change of heart failure medical or device therapies during the study period.
3. Absence of non-elective hospitalizations in the previous 2 weeks
4. At optimal volume status by symptoms, exam, and dry weight.
5. Serum potassium ≤ 5.0 mmol/L
6. Serum sodium ≥ 130 mEq/L
7. Age \> 18 years
8. Hemoglobin ≥8 g/dL
9. Objective evidence of diuretic resistance to a 10mg bumetanide challenge, defined as:
1. FENa \<10% and total sodium output \<150mmol and
2. At least one of the following criteria:
1\. 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
Exclusion Criteria
2. 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,
3. 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).
4. Hemoglobin \< 8 g/dL or symptomatic anemia
5. Pregnant or breastfeeding
6. Inability to give written informed consent or comply with study protocol or follow-up visits
7. Chronic urinary retention limiting ability to perform timed urine collection procedures
8. On Lithium therapy
9. On pimozide or thioridazine
10. Diagnosis of liver failure
11. Contraindications or allergy to sulfonamides
12. Any contraindication to thiazide diuretic or allergy to thiazide or bendroflumethiazide
18 Years
ALL
No
Sponsors
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
NIH
Yale University
OTHER
Responsible Party
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Jeffrey Testani
Associate Professor of Medicine
Principal Investigators
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Jeffrey Testani
Role: PRINCIPAL_INVESTIGATOR
Yale University
Locations
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Yale University
New Haven, Connecticut, United States
Countries
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Central Contacts
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Facility Contacts
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Veena Rao
Role: primary
Other Identifiers
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2000034315
Identifier Type: -
Identifier Source: org_study_id
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