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

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ClinicalTrials.gov Identifier: NCT03027960
Recruitment Status : Enrolling by invitation
First Posted : January 23, 2017
Last Update Posted : January 17, 2018
Sponsor:
Collaborator:
Boehringer Ingelheim
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Heart Failure Type II; Diabetes Drug: Empagliflozin Drug: Placebo Oral Capsule Phase 2

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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 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 : June 27, 2017
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : June 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure

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




Primary Outcome Measures :
  1. urine sodium concentrations via ion selective electrodes [ Time Frame: 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 [ Time Frame: 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03027960


Locations
United States, Connecticut
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

Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT03027960     History of Changes
Other Study ID Numbers: 2000020019
First Posted: January 23, 2017    Key Record Dates
Last Update Posted: January 17, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
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:
Empagliflozin
Heart Failure
Diabetes Mellitus, Type 2
Heart Diseases
Cardiovascular Diseases
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Diuretics
Hypoglycemic Agents
Physiological Effects of Drugs
Natriuretic Agents