This is a 60-patient randomized, double-blind, placebo-controlled mechanistic study to understand the utility of empagliflozin in worsening heart failure (HF) patients with or without diabetes. Participants will be randomized to empagliflozin or placebo for 6 weeks, followed by a crossover of placebo patients to active therapy at 6 weeks-12 weeks.
This is a 60-patient randomized, double-blind, placebo-controlled mechanistic study to understand the utility of empagliflozin in worsening heart failure (HF) patients with or without diabetes. The broad study design aims to evaluate change in gold standard determined body fluid spaces, sodium avidity, and cardio-renal biomarkers longitudinally in patients treated with placebo vs. empagliflozin over a 6 week period. Primary analysis of the randomized intervention will occur during the 6 week double blind period. Crossover of placebo patients to active therapy from 6-12 weeks will provide additional exploratory mechanistic data at low incremental cost and provide added benefit to enrollment of the study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
TRIPLE
Enrollment
60
Empagliflozin 10mg
Empagliflozin matched placebo tablet
Yale New Haven Hospital
New Haven, Connecticut, United States
RECRUITINGYale University
New Haven, Connecticut, United States
RECRUITINGNatriuretic effect of empagliflozin or placebo as an adjuvant to loop diuretic therapy
The natriuretic effect (urine sodium concentration) of each arm with loop diuretic therapy will be measured by the mmols of sodium excreted on day 1.
Time frame: Day 1
Change in plasma volume from baseline to 7 days
Chronic effects of empagliflozin or placebo to the loop diuretic will be assessed by measuring the change in plasma volume \[ml\] from Day 1 to Day 7, using I-131 albumin
Time frame: Day 1 and Day 7
Change in total body water from baseline to 7 days
Chronic effects of empagliflozin or placebo to the loop diuretic will be assessed by measuring the change in total body water \[liters\] from Day 1 to Day 7, using heavy water \[D2O)
Time frame: Day 1 and Day 7
Change in Chronic effects of empagliflozin vs placebo on plasma volume
Chronic effects of empagliflozin vs placebo on change in plasma volume \[ml\] will be measured on Day 1 and Day 42, using I-131 albumin
Time frame: Day 1 and day 42
Change in Chronic effects of empagliflozin vs placebo on change in total body water
Chronic effects of empagliflozin vs placebo on change in total body water \[liters\] will be measured on Day 1 and Day 42, using heavy water \[D2O\]
Time frame: Day 1 and day 42
Change in Chronic effects of empagliflozin on change in plasma volume during the open label extension.
Changes in plasma volume\[ml\] from Day 1 to Day 84 will be assessed during the open label extension, using I-131 albumin
Time frame: Day 1 up to Day 84
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Change in Chronic effects of empagliflozin on change in total body water during the open label extension.
Changes in total body water \[liters\] from Day 1 to Day 84 will be assessed during the open label extension, using heavy water \[D2O\]
Time frame: Day 1 up to Day 84