ToRsemide compArisoN with furoSemide FOR Management of Heart Failure (TRANSFORM-HF)
Age: 18 - 85 years
Healthy Subjects: No
Recruitment Status: Recruiting
Start Date: January 11, 2019
End Date: July 16, 2019
An approximately 6000-patient, randomized, unblinded, two-arm, multicenter clinical trial comparing torsemide with furosemide among patients hospitalized for heart failure.
1:1 randomization to either oral torsemide OR oral furosemide (dosing at discretion of local provider with dose equivalency guidance provided)
This study will be a randomized, unblinded, two-arm, multi-center clinical trial of patients hospitalized for heart failure. Approximately 6,000 patients will be enrolled in the trial. Patients will be randomized 1:1 to either oral torsemide OR oral furosemide prior to hospital discharge. 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 20 mg or furosemide 40-80 mg. Providers will be asked to document their planned initial dose and dosing frequency of torsemide and furosemide prior to patient randomization to assess the exact conversion factor being utilized. Randomization can occur at any time before hospital discharge at the discretion of the healthcare provider. If patients receive intravenous diuretic therapy during the index hospitalization, it is expected that randomization will occur near the time of transition to oral loop diuretic therapy or after the patient has successfully transitioned to oral loop diuretic therapy. Following randomization, the study medication is expected to constitute the oral diuretic therapy for the remainder of the hospitalization, with the expectation for patients to receive at least 1 dose of study medication prior to discharge. Patients will be prescribed the randomized study medication at time of index hospital discharge.
Post-discharge 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. The primary endpoint will be all cause mortality over the follow-up period. Patients will receive follow-up per standard care without any additional study-specific visits. All patients will have 30-day, 6-month, and 12-month post-randomization phone contacts performed by the Duke Clinical Research Institute (DCRI) Call Center for assessment of vital status interval hospitalizations, concomitant HF medications, adherence, quality of life, and symptoms of depression. As an additional mechanism to safeguard against hospitalization under-reporting, the DCRI Call Center will initiate a medical record query 12 months after patient randomization to screen for hospitalizations at the enrolling center and potential treating hospitals identified by the patient. The National Death Index (NDI) will be searched during follow-up and prior to study close-out.
1) Patient hospitalized (≥ 24 hours or over a change in calendar date) with worsening of chronic heart failure, or new diagnosis of heart failure AND meets 1 of the following criteria:
a. Has a left ventricular ejection fraction (EF) ≤40% within 24 months prior to and including index hospitalization by any method (with most recent value used to determine eligibility)
b. Has an elevated natriuretic peptide level (either NT-pro-B-type natriuretic peptide or B-type natriuretic peptide) during index hospitalization as measured by local laboratory
2) Plan for a daily outpatient oral loop diuretic regimen upon hospital discharge with anticipated need for long-term loop diuretic use
3) ≥ 18 years of age
4) Signed informed consent
1) End-stage renal disease requiring renal replacement 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
6) Malignancy or other non-cardiac condition limiting life expectancy to <12 months
7) Known hypersensitivity to furosemide, torsemide, or related agents