Empagliflozin in Heart Failure: Diuretic and Cardio-Renal Effects
- Conditions
- Type II; DiabetesHeart Failure
- Interventions
- Drug: Placebo Oral Capsule
- Registration Number
- NCT03027960
- Lead Sponsor
- Yale University
- Brief Summary
The investigators propose a small pilot proof of concept study to not only prove the existence of, but also probe the mechanisms underlying cardio-renal effects of empagliflozin in patients with heart failure. The investigators propose a 50 patient randomized, double-blind, placebo-controlled crossover study with patients with stable HF, type II diabetes and an eGFR \>45ml/min/1.73 m2 who are chronically receiving loop diuretics.
- Detailed Description
Study Objectives
1. Study the acute/short term effect and cardio-renal mechanisms of sodium-glucose cotransporter 2 (SGLT2) inhibition in patients with heart failure.
2. Determine the effect of chronic combined SLLGT2 and loop diuretic exposure in patients with heart failure.
Primary Outcomes
1. Aim 1 (Acute): Determine if acute SGLT2 inhibition will improve the natriuretic effect of a loop diuretic compared to placebo.
2. Aim 2 (Chronic): Determine the effect of 14 days of SGLT2 inhibition on blood volume.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 21
- Stable HF as defined by:
- No hospitalization for >60 days
- Stable HF medications for >=2 weeks, and stable diuretics for 4 weeks
- Opinion of HF cardiologist that the patient is at their optimal volume status
- Chronic daily oral loop diuretic dose >=20mg furosemide equivalents
- Diagnosis of type II diabetes
- Patient monitors blood glucose regularly at home
- eGFR >=45 mL/min/1.73 m2
- >=18 years old
- Active titration of chronic HF medications expected during the study period
- Use of a non-loop diuretic, aside from an aldosterone antagonist (<=25mg spironolactone or <=50mg eplerenone)
- Critical stenotic valvular disease, complex congenital heart disease, or prior heart transplant
- History of diabetic ketoacidosis, "brittle" diabetes, and/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 bladder dysfunction, incontinence, pyelonephritis, urosepsis, or frequent urinary tract infections
- Anemia (defined as hemoglobin <8g/dL)
- Pregnancy or breastfeeding
- History of serious hypersensitivity
- Participation in another trial with an investigational drug within the 30 days prior to informed consent
- Use of another SGLT-2 inhibitor
- Appears unlikely, or unable to participate in the required study procedures, as assessed by the study PI or research RN (ex: clinically-significant psychiatric, addictive, or neurological disease)
- Inability to give written informed consent or follow study protocol
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Placebo, then empagliflozin Placebo Oral Capsule Patients are randomized upon enrollment to determine whether they take empagliflozin or the matched placebo during the first 2-week treatment phase of the study. All patients then undergo a 2-week "washout period" before crossing over to the alternate therapy. Empagliflozin, then Placebo Placebo Oral Capsule Patients are randomized upon enrollment to determine whether they take empagliflozin or the matched placebo during the first 2-week treatment phase of the study. All patients then undergo a 2-week "washout period" before crossing over to the alternate therapy. Placebo, then empagliflozin Empagliflozin Patients are randomized upon enrollment to determine whether they take empagliflozin or the matched placebo during the first 2-week treatment phase of the study. All patients then undergo a 2-week "washout period" before crossing over to the alternate therapy. Empagliflozin, then Placebo Empagliflozin Patients are randomized upon enrollment to determine whether they take empagliflozin or the matched placebo during the first 2-week treatment phase of the study. All patients then undergo a 2-week "washout period" before crossing over to the alternate therapy.
- Primary Outcome Measures
Name Time Method urine sodium concentrations via ion selective electrodes 36 days Determine if acute SGLT2 inhibition will improve the natriuretic effect of a loop diuretic compared to placebo.
Measuring the natriuretic effect of a loop diuretic (placebo v acute SGLT2 inhibition) via urine sodium output.
- Secondary Outcome Measures
Name Time Method blood volume 14 days Determine the effect of 14 days of SGLT2 inhibition on blood volume.
Daxor Blood Volume Sample Collection
1. Volumex Injection: The Volumex tracer (radiolabeled albumin) is injected as an intravenous bolus (IV-push). (As soon as the tracer injection begins, a stopwatch is started and never zeroed out. Running times are used for the entire procedure).
2. Serial Blood Collection A series of 5 post-Volumex blood samples is collected, after tracer injection, allowing for complete mixing in the bloodstream.
3. Sample Timing: Samples are ideally spaced \~6 minutes apart, and are collected approximately 12, 18, 24, 30 and 36 minutes after Volumex administration.
Trial Locations
- Locations (1)
Yale New Haven Hospital
🇺🇸New Haven, Connecticut, United States