Ertugliflozin in Chronic Heart Failure

NCT ID: NCT04438213

Last Updated: 2025-10-08

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-10
• Study Completion Date: 2025-12-30

Brief Summary

The purpose of this study is to determine the effects on heart failure signs and symptoms of the use of either ertugliflozin, metolazone or placebo, in conjunction with intravenous loop diuretic use in acute settings and chronic oral loop diuretic therapy.

There are two general purposes for this study. The proposed study is both larger and more rigorous than essentially all PK/PD studies that form the basis of current practice with loop diuretics as well as all studies looking at add-on thiazide therapy (current guideline-recommended adjuvant). The second is to generate a mechanistic understanding of the pleotropic cardio-renal factors with chronic therapy that differentiate ertugliflozin from traditional diuretics particularly in how they maintain reduced blood volume without the complication of over-diuresis and volume depletion.

Detailed Description

This is a randomized placebo controlled mechanistic study to understand the utility of ertugliflozin in heart failure patients with or without diabetes, compared to both placebo and the active control metolazone. The broad study design will be designed around evaluation of change in gold standard determined body fluid spaces (blood volume, extracellular fluid, total body water), administering a sodium chloride challenge, and collecting the necessary biospecimens to test our hypotheses. The general study design will randomize to ertugliflozin vs. placebo for a total therapy of 6 weeks.

Conditions

Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Ertugliflozin

Participants will be randomized to six weeks of treatment with either ertugliflozin, metolazone, or a placebo

Group Type: EXPERIMENTAL

Ertugliflozin

Intervention Type: DRUG

Participants will be randomized to six weeks of treatment with either ertugliflozin, metolazone, or a placebo

Metolazone

Participants will be randomized to six weeks of treatment with either ertugliflozin, metolazone, or a placebo

Group Type: EXPERIMENTAL

Metolazone

Intervention Type: DRUG

Participants will be randomized to six weeks of treatment with either ertugliflozin, metolazone, or a placebo

Placebo

Participants will be randomized to six weeks of treatment with either ertugliflozin, metolazone, or a placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Participants will be randomized to six weeks of treatment with either ertugliflozin, metolazone, or a placebo

Interventions

Ertugliflozin

Participants will be randomized to six weeks of treatment with either ertugliflozin, metolazone, or a placebo

Intervention Type: DRUG

Metolazone

Participants will be randomized to six weeks of treatment with either ertugliflozin, metolazone, or a placebo

Intervention Type: DRUG

Placebo

Participants will be randomized to six weeks of treatment with either ertugliflozin, metolazone, or a placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. A clinical diagnosis of chronic heart failure (either systolic or diastolic)

2. Chronic daily oral loop diuretic dose use

3. eGFR ≥20 mL/min/1.73 m2

4. English speaking participants only

5. Signed informed consent

Exclusion Criteria

1. Current use or plan to initiate renal replacement therapy or ultrafiltration

2. Significant bladder dysfunction or urinary incontinence

3. Inability to comply with the serial urine collection procedures

4. Current use of a thiazide or thiazide like diuretics or use within 5 half-lives of the drug, including metolazone

5. Current use of a SGLT-2 inhibitor, or in the treating provider's judgement, contraindication to be withdrawn from current use of an SGLT-2 inhibitor

6. Prior heart transplant, critical stenotic valvular disease or complex congenital heart

7. 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 3 months

8. History of or current urosepsis or frequent urinary tract infections

9. Anemia with hemoglobin <8g/dL (due to required phlebotomy for the study)

10. Pregnancy or breastfeeding

11. 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)

12. Inability to give written informed consent or follow study protocol

13. Severe peripheral artery disease, previous amputation, or threatened amputation

14. Life expectancy < 3 months

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jeffrey Testani, MD

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

Yale School of Medicine

New Haven, Connecticut, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Veena Rao, PHD

Role: CONTACT

veena.s.rao@yale.edu

(203) 737-3571

Other Identifiers

MISP59625

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

2000027951

Identifier Type: -

Identifier Source: org_study_id