Clinical trial NCT05553938: Effects of Acute and Chronic Empagliflozin Heart Failure
Official title: Renal Mechanistic Effects of Acute and Chronic Empagliflozin in Heart Failure
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Heart Failure
Lead sponsor: Yale University
Sponsor class: OTHER
First posted: 2022-09-26
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention 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.)
Primary purpose: OTHER

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.

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)

Primary outcomes:
measure: Natriuretic effect of empagliflozin or placebo as an adjuvant to loop diuretic therapy
timeFrame: Day 1
measure: Change in plasma volume from baseline to 7 days
timeFrame: Day 1 and Day 7
measure: Change in total body water from baseline to 7 days
timeFrame: Day 1 and Day 7
Secondary outcomes:
measure: Change in Chronic effects of empagliflozin vs placebo on plasma volume
timeFrame: Day 1 and day 42
measure: Change in Chronic effects of empagliflozin vs placebo on change in total body water
timeFrame: Day 1 and day 42
measure: Change in Chronic effects of empagliflozin on change in plasma volume during the open label extension.
timeFrame: Day 1 up to Day 84
measure: Change in Chronic effects of empagliflozin on change in total body water during the open label extension.
timeFrame: Day 1 up to Day 84
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: New Haven
country: United States
facility: Yale University
state: Connecticut
Study officials:
affiliation: Yale University
name: Jeffrey Testani, MD
role: PRINCIPAL_INVESTIGATOR
References: