Comparing Natriuretic Effects of ER Torsemide to IR Torsemide in Patients With Heart Failure
brief summary
The primary objective of this study is to learn whether a morning dose of extended-release torsemide enhances renal sodium excretion after lunch (4-8 hours after dosing) compared to immediate-release torsemide. This is a randomized, double-blind, crossover study in patients with heart failure who are on a stable dose of a loop diuretic. The primary endpoint will be urinary sodium excretion (4-8 hours after dosing). This will be compared between the extended-release arm and the immediate-release arm to assess the efficacy of prolonged diuretic action. In addition, urinary potassium and creatinine excretion and creatinine clearance will be measured in all urine samples as the safety endpoints.
detailed description
Research Plan
Study Design
This is a double-blind, double-dummy, two-period, two-arm, randomized, crossover study.
Initial Study Procedures
Identification of Participants: Patients with a known history of stable heart failure (HF) for at least one month will be identified through healthcare records at clinical site, heart failure clinic, nephrology clinic, and other relevant clinics.
Treatment Arms and Crossover Design
* Arm 1: Approximately half of the participants will receive 20 mg IR torsemide followed by 24 mg ER torsemide or 40mg IR torsemide followed by 48 mg ER torsemide (6-10 days each). * Arm 2: The other half will receive 24 mg ER torsemide followed by 20 mg IR torsemide, or 48 mg ER torsemide followed by 40 mg IR torsemide (6-10 days each). * Dose Conversion:
o Patients on 20-40 mg furosemide will be converted to 20 mg IR torsemide or 24 mg ER torsemide.
o Patients on 60-80 mg furosemide will be converted to 40 mg torsemide (two 20 mg tablets) or 48 mg ER torsemide (two 24 mg tablets). * Patients on 1 mg bumetanide will be converted to 20 mg IR torsemide or 24 mg ER torsemide, while those on 2 mg bumetanide will be converted to 40 mg torsemide or 48 mg ER torsemide. * Double-Dummy Design: To maintain blinding, participants will also receive placebo corresponding to the medications in their arm, ensuring that participants and investigators remain unaware of their treatment assignment. * Dietary Instructions: Participants will be instructed to follow a low-sodium diet with a daily intake of approximately 3 grams of sodium throughout the study period.
Test Day Procedures
The test day will occur on the last day of each treatment period, with participants staying at the site for 9-10 hours (no overnight stay). The study staff undertake the following:
* Medication Compliance: Collect study medications for pill count and assess compliance. * Dosing:
* A standard breakfast will be served 30 minutes before dosing, and participants will be instructed to complete it within 30 minutes.
official title
A Randomized, Two-Period, Two-Arm, Double-Dummy, Crossover Study to Compare Natriuretic Effects of Extended Release Torsemide to Immediate Release Torsemide in Patients With Heart Failure (NEXT-HF)