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Empagliflozin in Worsening Heart Failure (EMPA WHF)

Primary Purpose

Heart Failure

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Empagliflozin 10 mg

Placebo

About this trial

This is an interventional other trial for Heart Failure

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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)

Sites / Locations

Yale New Haven HospitalRecruiting
Yale UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Empagliflozin

Placebo, Then Empagliflozin

Arm Description

Empagliflozin 10 mg daily for weeks 1-6

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

Outcomes

Primary Outcome Measures

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.

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

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)

Secondary Outcome Measures

Change in Chronic effects of empagliflozin vs placebo on plasma volume

Chronic effects of empagliflozin vs placebo on change in plasma volume [ml] will be measured on Day 1 and Day 42, using I-131 albumin

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

Chronic effects of empagliflozin vs placebo on change in total body water [liters] will be measured on Day 1 and Day 42, using heavy water [D2O]

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

Changes in plasma volume[ml] from Day 1 to Day 84 will be assessed during the open label extension, using I-131 albumin

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

Changes in total body water [liters] from Day 1 to Day 84 will be assessed during the open label extension, using heavy water [D2O]

Full Information

NCT ID

NCT05553938

First Posted

September 21, 2022

Last Updated

August 16, 2023

Sponsor

Yale University

1. Study Identification

Unique Protocol Identification Number

NCT05553938

Brief Title

Empagliflozin in Worsening Heart Failure

Acronym

EMPA WHF

Official Title

Empagliflozin in Worsening Heart Failure: Cardio-Renal and Diuretic Effects

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Recruiting

Study Start Date

August 4, 2023 (Actual)

Primary Completion Date

November 2023 (Anticipated)

Study Completion Date

November 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Yale University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

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.

Detailed Description

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. The broad study design aims to evaluate change in gold standard determined body fluid spaces, sodium avidity, and cardio-renal biomarkers longitudinally in patients treated with placebo vs. empagliflozin over a 6 week period. Primary analysis of the randomized intervention will occur during the 6 week double blind period. Crossover of placebo patients to active therapy from 6-12 weeks will provide additional exploratory mechanistic data at low incremental cost and provide added benefit to enrollment of the study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Heart Failure

7. Study Design

Primary Purpose

Other

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Model Description

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.)

Masking

ParticipantCare ProviderInvestigator

Masking Description

Double-blind

Allocation

Randomized

Enrollment

60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Empagliflozin

Arm Type

Experimental

Arm Description

Empagliflozin 10 mg daily for weeks 1-6

Arm Title

Placebo, Then Empagliflozin

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Empagliflozin 10 mg

Intervention Description

Empagliflozin 10mg

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Empagliflozin matched placebo tablet

Primary Outcome Measure Information:

Title

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

Description

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.

Time Frame

Day 1

Title

Change in plasma volume from baseline to 7 days

Description

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

Time Frame

Day 1 and Day 7

Title

Change in total body water from baseline to 7 days

Description

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)

Time Frame

Day 1 and Day 7

Secondary Outcome Measure Information:

Title

Change in Chronic effects of empagliflozin vs placebo on plasma volume

Description

Chronic effects of empagliflozin vs placebo on change in plasma volume [ml] will be measured on Day 1 and Day 42, using I-131 albumin

Time Frame

Day 1 and day 42

Title

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

Description

Chronic effects of empagliflozin vs placebo on change in total body water [liters] will be measured on Day 1 and Day 42, using heavy water [D2O]

Time Frame

Day 1 and day 42

Title

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

Description

Changes in plasma volume[ml] from Day 1 to Day 84 will be assessed during the open label extension, using I-131 albumin

Time Frame

Day 1 up to Day 84

Title

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

Description

Changes in total body water [liters] from Day 1 to Day 84 will be assessed during the open label extension, using heavy water [D2O]

Time Frame

Day 1 up to Day 84

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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)

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Katherine Keith

Phone

2037373571

katherine.keith@yale.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Veena Rao, PHD

Phone

2037373571

veena.s.rao@yale.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jeffrey Testani, MD

Organizational Affiliation

Yale University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Yale New Haven Hospital

City

New Haven

State/Province

Connecticut

ZIP/Postal Code

06520

Country

United States

Individual Site Status

Recruiting

Facility Name

Yale University

City

New Haven

State/Province

Connecticut

ZIP/Postal Code

06520

Country

United States

Individual Site Status

Recruiting

12. IPD Sharing Statement

Plan to Share IPD

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Empagliflozin in Worsening Heart Failure

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