EMPA: Empagliflozin in Heart Failure: Diuretic and Cardio-Renal Effects

• Sponsor: Yale University (Other)
• Overall Status: Completed
• CT.gov ID: NCT03027960
• Collaborator: Boehringer Ingelheim (Industry)
• Enrollment: 21
• Location: 1
• Arms: 2
• Actual Duration (Months): 23.1
• Patients Per Site Per Month: 0.9

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Heart Failure; Type II; Diabetes	Drug: Empagliflozin; Drug: Placebo Oral Capsule	Phase 1

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Care Provider)
• Primary Purpose: Treatment
• Official Title: Empagliflozin in Heart Failure: Diuretic and Cardio-Renal Effects
• Actual Study Start Date: Jun 27, 2017
• Actual Primary Completion Date: May 14, 2019
• Actual Study Completion Date: Jun 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Placebo, then 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.	Drug: Empagliflozin; 10mg empagliflozin for a 2-week period; Drug: Placebo Oral Capsule; 10 mg placebo for a 2-week period
Experimental: Empagliflozin, then Placebo 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.	Drug: Empagliflozin; 10mg empagliflozin for a 2-week period; Drug: Placebo Oral Capsule; 10 mg placebo for a 2-week period

Outcome Measures

Primary Outcome Measures

1. 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

1. blood volume [14 days]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yale New Haven Hospital	New Haven	Connecticut	United States	06511

Sponsors and Collaborators

• Yale University
• Boehringer Ingelheim

Investigators

• Principal Investigator: Jeffrey Testani, MD, Yale University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT03027960
• Other Study ID Numbers: 2000020019
• First Posted: Jan 23, 2017
• Last Update Posted: Jun 26, 2020
• Last Verified: Jun 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Yale University: cardio-renal
• Additional relevant MeSH terms: Heart Failure; Diabetes Mellitus, Type 2; Empagliflozin

Study Results

No Results Posted as of Jun 26, 2020