Ertugliflozin in Chronic Heart Failure

Heart Failure Clinical Trial

Official title:

Ertugliflozin in Chronic Heart Failure: Cardio-renal and Diuretic Effects

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04438213
• Other study ID #: 2000027951
• Secondary ID: MISP59625
• Status: Recruiting
• Phase: Phase 2
• Start date: March 10, 2021
• Est. completion date: July 2025

Study information

• Verified date: May 2024
• Source: Yale University
• Contact: Veena Rao, PHD
• Phone: (203) 737-3571
• Email: veena.s.rao[@]yale.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

This is a randomized placebo controlled mechanistic study to understand the utility of ertugliflozin in acute and post-acute hospitalized 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 early during IV diuretic therapy with continuation post discharge for a total therapy of 6 weeks.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: July 2025
• Est. primary completion date: January 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. A clinical diagnosis of ADHF with at least one objective sign of volume overload (rales, edema, elevated JVP, or preadmission weight gain)

2. As judged by the treating physician, a projected need and ability to tolerate treatment with an extended need for IV diuretics with the goal of significant fluid removal (i.e., goal >1L/day net fluid loss)

3. Chronic daily oral loop diuretic dose > or equal to 20mg furosemide equivalents for at least one month prior to admission

4. eGFR 30 mL/min/1.73 m2

5. Signed informed consent

Exclusion Criteria:

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

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

6. 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

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

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

9. Pregnancy or breastfeeding

Related Conditions & MeSH terms

• Heart Failure

Intervention

Drug:
• Ertugliflozin
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
• Placebo
Participants will be randomized to six weeks of treatment with either ertugliflozin, metolazone, or a placebo

Locations

Country	Name	City	State
United States	Yale School of Medicine	New Haven	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
Yale University	Merck Sharp & Dohme LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Natriuretic effect of adjuvant to loop diuretic therapy	The natriuretic effect (urine sodium concentration) of each arm with loop diuretic therapy will be measured by the urine sodium output.	1 day
Primary	Change from baseline to day 7 of total body water by add-on to loop diuretic therapy (Chronic)	The primary outcome of the chronic effects of add-on placebo, thiazide-like diuretic, or SGLT2 inhibitor is to determine the change in total body water from baseline to day 7	7 days
Primary	Change from baseline to 6 weeks total body water by add-on to loop diuretic therapy (Chronic)	The primary outcome of the chronic effects of add-on placebo, thiazide-like diuretic, or SGLT2 inhibitor is to determine the change in total body water from baseline to 6 weeks.	6 weeks