Ertugliflozin in Chronic Heart Failure

NCT04438213 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 2000027951MISP59625
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Heart Failure

Keywords

Ertugliflozin; Metolazone

Outcome Measures

Primary Outcomes (3)

• Change from baseline to day 7 of plasma volume by add-on to loop diuretic therapy

  The primary outcome of the chronic effects of add-on placebo, thiazide-like diuretic, or SGLT2 inhibitor is to determine the change in plasma volume from baseline to day 7

  7 days

• Change from baseline to 6 weeks of plasma volume by add-on to loop diuretic therapy

  The primary outcome of the chronic effects of add-on placebo, thiazide-like diuretic, or SGLT2 inhibitor is to determine the change in plasma volume from baseline to 6 weeks

  6 weeks

• Natriuretic effect of adjuvant to loop diuretic therapy

  The natriuretic effect of each arm with loop diuretic therapy will be measured by the urine sodium output and FeNa.

  1 day

Study Arms (3)

Ertugliflozin

EXPERIMENTAL

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

Drug: Ertugliflozin

Metolazone

EXPERIMENTAL

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

Drug: Metolazone

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Ertugliflozin DRUG

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

Ertugliflozin

Metolazone DRUG

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

Metolazone

Placebo DRUG

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

Placebo

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 chronic heart failure (either systolic or diastolic)
• Chronic daily oral loop diuretic dose use
• eGFR ≥20 mL/min/1.73 m2
• English speaking participants only
• Signed informed consent

You may not qualify if:

• Current use or plan to initiate renal replacement therapy or ultrafiltration
• Significant bladder dysfunction or urinary incontinence
• Inability to comply with the serial urine collection procedures
• Current use of a thiazide or thiazide like diuretics or use within 5 half-lives of the drug, including metolazone
• 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
• Prior heart transplant, critical stenotic valvular disease or complex congenital heart
• 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
• History of or current urosepsis or frequent urinary tract infections
• Anemia with hemoglobin \<8g/dL (due to required phlebotomy for the study)
• 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)
• Inability to give written informed consent or follow study protocol
• Severe peripheral artery disease, previous amputation, or threatened amputation
• Life expectancy \< 3 months

Sponsors & Collaborators

• Yale University: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Yale School of Medicine

New Haven, Connecticut, 06510, United States

RECRUITING

MeSH Terms

Conditions

Heart Failure

Interventions

ertugliflozin; Metolazone

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Quinazolinones; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Jeffrey Testani, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Veena Rao, PHD

CONTACT

(203) 737-3571; veena.s.rao@yale.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2020
• First Posted: June 18, 2020
• Study Start: March 10, 2021
• Primary Completion: December 30, 2025
• Study Completion: December 30, 2025
• Last Updated: October 8, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)