Mechanisms of Diuretic Resistance in Heart Failure, Aim 2
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Placebo, Amiloride, Bendroflumethiazide.
- Who it may be relevant to
- Registry conditions: Heart Failure. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
Randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations placebo/placebo, bendroflumethiazide/placebo, amiloride/placebo, and bendroflumethiazide/amiloride added to bumetanide.
Detailed 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.
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.
Interventions
- Drug 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 - Drug 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 - Drug 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
Primary outcome measures
- Change in peak FENa from bumetanide monotherapy to bumetanide plus combination therapy [Time frame: 21 days]
- Change in distal sodium reabsorption [Time frame: 21 days]
- Correlation between distal sodium reabsorption and uEV pendrin/CD9 [Time frame: 21 days]
Eligibility criteria
Inclusion criteria
- Clinical diagnosis of HF
- No plan for titration/change of heart failure medical or device therapies during the study period.
- Absence of non-elective hospitalizations in the previous 2 weeks
- At optimal volume status by symptoms, exam, and dry weight.
- Serum potassium ≤ 5.0 mmol/L
- Serum sodium ≥ 130 mEq/L
- Age > 18 years
- Hemoglobin ≥8 g/dL
- Objective evidence of diuretic resistance to a 10mg bumetanide challenge, defined as:
- FENa <10% and total sodium output <150mmol and
- 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
- GFR <20 ml/min/1.73m2 using the CKD-EPI equation or use of renal replacement therapies
- 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,
- 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).
- Hemoglobin < 8 g/dL or symptomatic anemia
- Pregnant or breastfeeding
- Inability to give written informed consent or comply with study protocol or follow-up visits
- Chronic urinary retention limiting ability to perform timed urine collection procedures
- On Lithium therapy
- On pimozide or thioridazine
- Diagnosis of liver failure
- Contraindications or allergy to sulfonamides
- Any contraindication to thiazide diuretic or allergy to thiazide or bendroflumethiazide
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Crossover
- Masking
- Triple blind
- Primary purpose
- Other
Study locations
United States · 1 center
- Yale University — New Haven
Identifiers
NCT: NCT05753059 · 2000034315 · 1R01DK130997-01