Torsemide Comparison With Furosemide for Management of Patients With Stable Heart Failure (TFO)

The study is designed to be a prospective, randomized study is to compare the effectiveness of two standard of care loop diuretics (furosemide versus torsemide) on clinical outcomes among patients currently on a stable dose of loop diuretics.

Study Overview

• Status: Active, not recruiting
• Conditions: Heart Failure
• Intervention / Treatment: Drug: Furosemide; Drug: Torsemide

Detailed Description

This study will be a randomized, unblinded, two-arm, multi-center clinical trial of patients receiving loop diuretics for treatment of heart failure in an outpatient clinic. This study will serve as additional enrollment for Cardio-Renal Effects of Torsemide vs. Furosemide: A TRANSFORMHF Mechanistic Sub-Study (HIC 2000025867) which is currently only enrolling patients admitted to the hospital for worsening heart failure. Thus allowing for expanded enrollment into HIC 2000025867 with a more diverse group of heart failure patients. Participants will be co-enrolled into this study and HIC 2000025867.

Patients will be randomized 1:1 to either oral torsemide OR oral furosemide (dosing at discretion of local provider with dose equivalency guidance provided). This study will include stable subjects seen at the outpatient setting. The initial and follow-up dosing of torsemide and furosemide will be at healthcare provider discretion, with the following conversion provided as a guide: 1 mg torsemide to 2-4 mg oral furosemide. For instance, a patient would receive torsemide 20mg or furosemide 40-80 mg. Providers will be asked to document their planned initial dose and dosing frequency of torsemide and furosemide Randomization will occur within thirty days after the consent process and at the discretion of the healthcare provider and research team. Following randomization, the study medication is expected to constitute the oral diuretic therapy for one year. Patients will be prescribed the randomized study medication on the day of randomization.

Dose adjustments will be at the discretion of the treating healthcare provider(s) with strategies in place to maintain prescription of and adherence to the randomized medication. All patients will have 30-day, and 12-month post-randomization phone contacts for assessment of vital status, interval hospitalizations, concomitant HF medications, adherence, and weight.

To achieve these goals, the investigators propose a multi-center 125-patient study that will also co-enroll into Transform Ancillary (HIC 2000025867) a mechanistic sub-study of this study and TRANSFORMHF.

• Study Type: Interventional
• Enrollment (Estimated): 125
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients with a diagnosis of heart failure and who have been on a stable dose of a diuretic for at least 30 days.
2. Plan for a daily outpatient oral loop diuretic regimen with anticipated need for long term loop diuretic use
3. ≥ 18 years of age
4. Signed informed consent

Exclusion Criteria:

1. End-stage renal disease requiring dialysis therapy
2. Inability or unwillingness to comply with the study requirements
3. History of heart transplant or actively listed for heart transplant
4. Implanted left ventricular assist device or implant anticipated <3 months
5. Pregnant or nursing women or women who are trying to conceive
6. Malignancy or other non-cardiac condition limiting life expectancy to <12 months
7. Known hypersensitivity to furosemide, torsemide, or related agents

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Furosemide; Furosemide, oral, dosage and frequency determined by treating physician or provider. 1 mg torsemide to 2-4 mg oral furosemide	Drug: Furosemide; Standard of care diuretic
Active Comparator: Torsemide; Torsemide, oral, dosage and frequency determined by treating physician or provider. 1 mg torsemide to 2-4 mg oral furosemide	Drug: Torsemide; Standard of care diuretic

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality, measured at 1 year.	All-cause mortality as measured by phone calls at 30 days and 1 year	One year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause hospitalization	All-cause hospitalization over one year	One year
Total hospitalizations	• Total hospitalizations over one year	One year
Change in weight	Change in weight over one year	One year

Collaborators and Investigators

• Sponsor: Yale University

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2021
• Primary Completion (Actual): June 30, 2023
• Study Completion (Estimated): August 14, 2024

Study Registration Dates

• First Submitted: October 13, 2021
• First Submitted That Met QC Criteria: October 13, 2021
• First Posted (Actual): October 26, 2021

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 26, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Sodium Potassium Chloride Symporter Inhibitors; Furosemide; Torsemide
• Other Study ID Numbers: 2000029589

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No