Recruiting
Phase 1

Diuretic Resistance

Sponsor:

Yale University

Code:

NCT05323487

Conditions

Heart Failure

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Bumetanide Injection

Study Details

Brief summary:

This study will employ a randomized order, double-blind, repeated measures dose ranging design. This design was chosen in order to generate multiple within-subject serial loop diuretic dose response exposures. The overall study schema will include 75 heart failure (HF) patients.

Conditions

Heart Failure

Study ID

NCT05323487

Start date

Jun 1, 2022

Status verified date

May, 2026

Completion date

May 1, 2027

Anticipated

Primary completion date

May 1, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 3 months.
  • At optimal volume status by symptoms, exam, and dry weight
  • Age > 18 years

Exclusion Criteria:

  • GFR <20 ml/min/1.73m2 using the Chronic Kidney Disease- Epidemiology (CKD-EPI)equation or use of renal replacement therapies
  • Use of any non-loop type diuretic in the last 14 days 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, Hydrochlorothiazide (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
  • 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

Study Design

Enrollment

75 participants

Anticipated

Allocation

Randomized

Intervention Model

Sequential

Primary purpose

Other

Interventions and Outcome Measures

Arms

active comparator: Bumetanide 10 mg

Randomized to doses 10 mg, 5 mg, 2.5 mg, 1.25 mg

active comparator: Bumetanide 5 mg

5 mg Randomized to doses 10 mg, 5 mg, 2.5 mg, 1.25 mg

active comparator: Bumetanide 2.5 mg

2.5 mg Randomized to doses 10 mg, 5 mg, 2.5 mg, 1.25 mg

active comparator: Bumetanide 1.25 mg

1.25 mg Randomized to doses 10 mg, 5 mg, 2.5 mg, 1.25 mg

Interventions

Bumetanide Injection

Participants in balance will present to the study site Day 0 and receive their first randomized dose of bumetanide (1.25mg, 2.5mg, 5mg, or 10mg) and undergo the bio-specimen collection protocol. They will return every 3 days, allowing 2 full days washout, to receive the other doses in random sequence.

Primary outcome measure

  • Change in fractional excretion of lithium(FELi) pre-diuretic to 1-hour post IV bumetanide infusion [ Time Frame: Baseline and 1 hour post bumetanide infusion. ]
  • Change in distal sodium reabsorption pre-diuretic to 1-hour post IV bumetanide infusion [ Time Frame: Baseline and 1 hour post bumetanide infusion. ]
  • Tubular diuretic efficiency at baseline [ Time Frame: Baseline ]
  • Ratio of A to F splice variant Messenger Ribonucleic Acid (mRNA )in urinary extracellular vesicles at baseline [ Time Frame: Baseline ]

Central Contacts and Locations

Central contacts

Veena Rao

2037373571veena.s.rao@yale.edu

Locations

Yale University

Recruiting

New Haven, Connecticut, United States, 06510

Contacts

Veena Rao

203-737-3571veena.s.rao@yale.edu

Principal Investigator:

Jeffrey Testani, MD

More Information

Sponsor

Yale University

Last update posted

May 22, 2026

Last verified

May, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Yale University on 2026-05-22.