Mechanisms of Diuretic Resistance in Heart Failure, Aim 2

Heart Failure Clinical Trial

— MsDR 2  

Official title:

Mechanisms of Diuretic Resistance in Heart Failure, Aim 2

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05753059
• Other study ID #: 2000034315
• Secondary ID: 1R01DK130997-01
• Status: Recruiting
• Phase: Phase 1
• Start date: August 10, 2023
• Est. completion date: June 2027

Study information

• Verified date: June 2024
• Source: Yale University
• Contact: Veena Rao
• Phone: 203-737-3571
• Email: veena.s.rao[@]yale.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations placebo/placebo, bendroflumethiazide/placebo, amiloride/placebo, and bendroflumethiazide/amiloride added to bumetanide.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: June 2027
• Est. primary completion date: June 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Chronic clinical diagnosis of HF with a documented ejection fraction <40%.

2. Use of beta blocker, ACE, ARB or neprilysin inhibitor (sacubitril/valsartan), aldosterone antagonist, and SGLT2 inhibitor at =50% guideline directed doses for 30 days with no plan for titration/change during the study period.

3. Chronic stable use of =80mg furosemide equivalents per day for = 30 days

4. Peak FENa < 5% following 10mg IV bumetanide challenge at the screening visit

5. Absence of hospitalizations in the previous 3 months.

6. At optimal volume status by symptoms, exam, and dry weight.

7. Serum potassium = 5.0 mmol/L

8. Serum sodium = 130 mEq/L

9. Age > 18 years

Exclusion Criteria:

1. GFR <20 ml/min/1.73m2

2. Use of any non-loop type diuretic in the last 14 days with the exclusion of low dose aldosterone antagonist (e.g., spironolactone =50 mg)

3. History of flash pulmonary edema or a "brittle" volume sensitive HF phenotype such as amyloid cardiomyopathy

4. Hemoglobin < 8 g/dL

5. Pregnant or breastfeeding

6. Inability to give written informed consent or comply with study protocol or follow-up visits

Related Conditions & MeSH terms

• Heart Failure

Intervention

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
• 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

Locations

Country	Name	City	State
United States	Yale University	New Haven	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
Yale University	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in peak FENa from bumetanide monotherapy to bumetanide plus combination therapy	Change in peak FENa from bumetanide monotherapy to bumetanide plus combination therapy	21 days
Primary	Change in distal sodium reabsorption	Change in distal sodium reabsorption (FELi minus FENa) from bumetanide monotherapy to bumetanide plus combination therapy	21 days
Primary	Correlation between distal sodium reabsorption and uEV pendrin/CD9	Correlation between distal sodium reabsorption (FELi minus FENa) and uEV pendrin/CD9	21 days