Effects of Acute and Chronic Empagliflozin Heart Failure

NCT05553938 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 2000033412
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 2

Brief Summary

This is a 60-patient randomized, double-blind, placebo-controlled mechanistic study to understand the utility of empagliflozin in worsening heart failure (HF) patients with or without diabetes. Participants will be randomized to empagliflozin or placebo for 6 weeks, followed by a crossover of placebo patients to active therapy at 6 weeks-12 weeks.

Conditions

Heart Failure

Outcome Measures

Primary Outcomes (3)

• Natriuretic effect of empagliflozin or placebo as an adjuvant to loop diuretic therapy

  The natriuretic effect (urine sodium concentration) of each arm with loop diuretic therapy will be measured by the mmols of sodium excreted on day 1.

  Day 1

• Change in plasma volume from baseline to 7 days

  Chronic effects of empagliflozin or placebo to the loop diuretic will be assessed by measuring the change in plasma volume \[ml\] from Day 1 to Day 7, using I-131 albumin

  Day 1 and Day 7

• Change in total body water from baseline to 7 days

  Chronic effects of empagliflozin or placebo to the loop diuretic will be assessed by measuring the change in total body water \[liters\] from Day 1 to Day 7, using heavy water \[D2O)

  Day 1 and Day 7

Secondary Outcomes (4)

• Change in Chronic effects of empagliflozin vs placebo on plasma volume

  Day 1 and day 42

• Change in Chronic effects of empagliflozin vs placebo on change in total body water

  Day 1 and day 42

• Change in Chronic effects of empagliflozin on change in plasma volume during the open label extension.

  Day 1 up to Day 84

• Change in Chronic effects of empagliflozin on change in total body water during the open label extension.

  Day 1 up to Day 84

Study Arms (2)

Empagliflozin

EXPERIMENTAL

Empagliflozin 10 mg daily for weeks 1-6

Drug: Empagliflozin 10 mg

Placebo, Then Empagliflozin

EXPERIMENTAL

Participants first receive matching placebo daily for weeks 1-6, then will receive Empagliflozin 10 mg daily for weeks 7-12

Drug: Empagliflozin 10 mg; Drug: Placebo

Interventions

Empagliflozin 10 mg DRUG

Empagliflozin 10mg

Empagliflozin; Placebo, Then Empagliflozin

Placebo DRUG

Empagliflozin matched placebo tablet

Placebo, Then Empagliflozin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A clinical diagnosis of worsening heart failure (worsening of congestive symptoms with current therapies) in the opinion of the investigator.
• A planned outpatient diuretic intervention (either up-titration of loop or addition of thiazide diuretic) for worsening heart failure per treating clinician. Diuretic intervention can occur via an unplanned in person visit (e.g., outpatient ambulatory clinic, emergency department, same day access visit) or via a telephone encounter (e.g., patient calling the clinic with reported weight gain and SOB that is prescribed uptitration of diuretic therapy).
• Estimated or reported weight gain of at least 5 lbs.
• Chronic daily oral loop diuretic dose ≥ 20mg furosemide equivalents for at least one month prior to enrollment
• Estimated GFR (eGFR) ≥ 20 mL/min/1.73 m2
• Age ≥ 18 years old
• Signed informed consent
• English speaking participants only

You may not qualify if:

• Need for heart failure hospitalization at the time of randomization
• Current use or plan to initiate renal replacement therapy
• Significant bladder dysfunction or urinary incontinence
• Inability to comply with the serial urine collection procedures
• Chronic use of natriuretic doses of thiazide diuretics (≥50mg hydrochlorothiazide or equivalent)
• Critical stenotic valvular disease, complex congenital heart disease or prior heart transplant
• History of type 1 diabetes, diabetic ketoacidosis, "brittle" diabetes or frequent hypoglycemia or severe hypoglycemic episodes requiring emergent intervention (ER visit or EMS response, glucagon administration or forced oral carbs) in the last 6 months
• History of or current urosepsis or frequent urinary tract infections
• Anemia with hemoglobin \<8g/dL (due to required phlebotomy for the study) or active bleeding
• Pregnancy or breastfeeding
• Appears unlikely or unable to participate in the required study procedures, as assessed by the study PI, study coordinator, or designee (ex: clinically-significant psychiatric, addictive, or neurological disease)

Sponsors & Collaborators

• Yale University: lead

Study Sites (2)

Yale New Haven Hospital

New Haven, Connecticut, 06520, United States

RECRUITING

Yale University

New Haven, Connecticut, 06520, United States

RECRUITING

MeSH Terms

Conditions

Heart Failure

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Jeffrey Testani, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Veena Rao, PHD

CONTACT

2037373571; veena.s.rao@yale.edu

Kara Otis

CONTACT

2037373571; kara.otis@yale.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double-blind
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Double blind placebo controlled, with crossover for placebo patients to active drug at 6 weeks. (At 6 weeks, participants are unblinded, and participants who received placebo will receive study drug.)

Study Record Dates

• First Submitted: September 21, 2022
• First Posted: September 26, 2022
• Study Start: August 4, 2023
• Primary Completion: November 1, 2025
• Study Completion: November 1, 2025
• Last Updated: December 18, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)