Clinical trial NCT03027960: Empagliflozin in Heart Failure: Diuretic and Cardio-Renal Effects
Official title: Empagliflozin in Heart Failure: Diuretic and Cardio-Renal Effects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Heart Failure
Type II; Diabetes
Keywords: cardio-renal
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: Boehringer Ingelheim
First posted: 2017-01-23
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: urine sodium concentrations via ion selective electrodes
timeFrame: 36 days
Secondary outcomes:
measure: blood volume
timeFrame: 14 days
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
Study officials:
affiliation: Yale University
name: Jeffrey Testani, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.