Empagliflozin in Heart Failure: Diuretic and Cardio-Renal Effects

NCT03027960 | Completed Phase 1 FDA Drug

• 1 other identifier: 2000020019
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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.

Conditions

Heart Failure; Type II; Diabetes

Keywords

cardio-renal

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• blood volume

  14 days

Study Arms (2)

Placebo, then empagliflozin

EXPERIMENTAL

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; Drug: Placebo Oral Capsule

Empagliflozin, then Placebo

EXPERIMENTAL

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; Drug: Placebo Oral Capsule

Interventions

Empagliflozin DRUG

10mg empagliflozin for a 2-week period

Empagliflozin, then Placebo; Placebo, then empagliflozin

Placebo Oral Capsule DRUG

10 mg placebo for a 2-week period

Empagliflozin, then Placebo; Placebo, then empagliflozin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Yale University: lead
• Boehringer Ingelheim: collaborator

Study Sites (1)

Yale New Haven Hospital

New Haven, Connecticut, 06511, United States

Location

Related Publications (2)

• Rao VS, Ivey-Miranda JB, Cox ZL, Moreno-Villagomez J, Maulion C, Bellumkonda L, Chang J, Field MP, Wiederin DR, Butler J, Collins SP, Turner JM, Wilson FP, Inzucchi SE, Wilcox CS, Ellison DH, Testani JM. Empagliflozin in Heart Failure: Regional Nephron Sodium Handling Effects. J Am Soc Nephrol. 2024 Feb 1;35(2):189-201. doi: 10.1681/ASN.0000000000000269. Epub 2023 Dec 11.

  PMID: 38073038 DERIVED

• Griffin M, Rao VS, Ivey-Miranda J, Fleming J, Mahoney D, Maulion C, Suda N, Siwakoti K, Ahmad T, Jacoby D, Riello R, Bellumkonda L, Cox Z, Collins S, Jeon S, Turner JM, Wilson FP, Butler J, Inzucchi SE, Testani JM. Empagliflozin in Heart Failure: Diuretic and Cardiorenal Effects. Circulation. 2020 Sep 15;142(11):1028-1039. doi: 10.1161/CIRCULATIONAHA.120.045691. Epub 2020 May 15.

  PMID: 32410463 DERIVED

MeSH Terms

Conditions

Heart Failure; Diabetes Mellitus, Type 2

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Jeffrey Testani, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2017
• First Posted: January 23, 2017
• Study Start: June 27, 2017
• Primary Completion: May 14, 2019
• Study Completion: June 1, 2019
• Last Updated: June 26, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)