RECRUITING

Mechanisms of Diuretic Resistance in Heart Failure, Aim 3

Conditions

Heart Failure Diuretic Resistance Diuretic Cardiomyopathy

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

Randomized double-blind placebo-controlled crossover study design

Official Title

Mechanisms of Diuretic Resistance in Heart Failure, Aim 3

Quick Facts

Study Start:2024-07-24

Study Completion:2028-03-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06209359

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Clinical diagnosis of heart failure * 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 months. * At optimal volume status by symptoms, exam, and dry weight. * Serum potassium ≤ 5.0 mmol/L * Serum sodium ≥ 130 milliequivalents/ liter (mEq/L) * Hemoglobin ≥8 g/dL * Age \>18 years * Objective evidence of diuretic resistance to a 10mg bumetanide challenge (screening visit may occur under this protocol or HIC2000032328 or HIC2000034315) defined as: * FENa \<10% and total sodium output \<150mmol * And at least one of the following criteria: * Chronic home furosemide dose greater than or equal to 80mg furosemide equivalents * eGFR \< 60ml/min * Serum chloride \<100mmol/L * FENa \<5% and total sodium output \<75mmol on the 2 hour	* Glomerular filtration rate (GFR) \<20 ml/min/1.73m2 * Use of any non-loop type diuretic in the last 7 days with the exclusion of low dose aldosterone antagonist (e.g., spironolactone ≤50 mg) * History of flash pulmonary edema or a "brittle" volume sensitive HF phenotype such as amyloid cardiomyopathy * Hemoglobin \< 8 g/dL * Pregnant or breastfeeding * Cirrhosis or known liver disease * History of metabolic or respiratory acidosis within 30 days * Use of metformin, acetazolamide, or any other agent that could predispose to acidosis * Patients who are on metformin may be enrolled if their metformin can be safely discontinued for the randomized treatment periods in each arm. Any participants who have consistently elevated blood glucose readings \> 200 mg/dL while inpatient will not be enrolled. * Serum bicarbonate level \<24mmol/L at screening visit * Venous potential of hydrogen(pH) \<7.35 at screening visit * Inability to give written informed consent or comply with study protocol or follow-up visits * 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

Inclusion Criteria

Exclusion Criteria

* Clinical diagnosis of heart failure
* 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 months.
* At optimal volume status by symptoms, exam, and dry weight.
* Serum potassium ≤ 5.0 mmol/L
* Serum sodium ≥ 130 milliequivalents/ liter (mEq/L)
* Hemoglobin ≥8 g/dL
* Age \>18 years
* Objective evidence of diuretic resistance to a 10mg bumetanide challenge (screening visit may occur under this protocol or HIC2000032328 or HIC2000034315) defined as:
* FENa \<10% and total sodium output \<150mmol
* And at least one of the following criteria:
* Chronic home furosemide dose greater than or equal to 80mg furosemide equivalents
* eGFR \< 60ml/min
* Serum chloride \<100mmol/L
* FENa \<5% and total sodium output \<75mmol on the 2 hour

* Glomerular filtration rate (GFR) \<20 ml/min/1.73m2
* Use of any non-loop type diuretic in the last 7 days with the exclusion of low dose aldosterone antagonist (e.g., spironolactone ≤50 mg)
* History of flash pulmonary edema or a "brittle" volume sensitive HF phenotype such as amyloid cardiomyopathy
* Hemoglobin \< 8 g/dL
* Pregnant or breastfeeding
* Cirrhosis or known liver disease
* History of metabolic or respiratory acidosis within 30 days
* Use of metformin, acetazolamide, or any other agent that could predispose to acidosis
* Patients who are on metformin may be enrolled if their metformin can be safely discontinued for the randomized treatment periods in each arm. Any participants who have consistently elevated blood glucose readings \> 200 mg/dL while inpatient will not be enrolled.
* Serum bicarbonate level \<24mmol/L at screening visit
* Venous potential of hydrogen(pH) \<7.35 at screening visit
* Inability to give written informed consent or comply with study protocol or follow-up visits
* 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

Contacts and Locations

Study Contact

Veena Rao, PHD

CONTACT

2037373571

veena.s.rao@yale.edu

Kara Otis

CONTACT

2037373571

kara.otis@yale.edu

Principal Investigator

Jeffrey Testani, MD

PRINCIPAL_INVESTIGATOR

Yale University

Study Locations (Sites)

Yale University

New Haven, Connecticut, 06510

United States

Collaborators and Investigators

Sponsor: Yale University

Jeffrey Testani, MD, PRINCIPAL_INVESTIGATOR, Yale University

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-07-24

Study Completion Date2028-03-01

Study Record Updates

Study Start Date2024-07-24

Study Completion Date2028-03-01

Terms related to this study

Keywords Provided by Researchers

Diuretic
Cardiomyopathy
Diuretic Resistance

Additional Relevant MeSH Terms

Heart Failure
Diuretic Resistance