Empagliflozin in Heart Failure: Diuretic and Cardio-Renal Effects

Heart Failure Clinical Trial

— EMPA  

Official title:

Empagliflozin in Heart Failure: Diuretic and Cardio-Renal Effects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03027960
• Other study ID #: 2000020019
• Status: Completed
• Phase: Phase 1
• Start date: June 27, 2017
• Est. completion date: June 1, 2019

Study information

• Verified date: June 2020
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: June 1, 2019
• Est. primary completion date: May 14, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Heart Failure
• Type II; Diabetes

Intervention

Drug:
• Empagliflozin
10mg empagliflozin for a 2-week period
• Placebo Oral Capsule
10 mg placebo for a 2-week period

Locations

Country	Name	City	State
United States	Yale New Haven Hospital	New Haven	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
Yale University	Boehringer Ingelheim

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	urine sodium concentrations via ion selective electrodes	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.	36 days
Secondary	blood volume	Determine the effect of 14 days of SGLT2 inhibition on blood volume.; Daxor Blood Volume Sample Collection; 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).; Serial Blood Collection A series of 5 post-Volumex blood samples is collected, after tracer injection, allowing for complete mixing in the bloodstream.; Sample Timing: Samples are ideally spaced ~6 minutes apart, and are collected approximately 12, 18, 24, 30 and 36 minutes after Volumex administration.	14 days