Heart Failure, Type II; Diabetes
Conditions
Keywords
cardio-renal
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.
Interventions
DRUGEmpagliflozin
10mg empagliflozin for a 2-week period
DRUGPlacebo Oral Capsule
10 mg placebo for a 2-week period
Sponsors
Boehringer Ingelheim
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| blood volume | 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. |
Countries
United States
Outcome results
None listed