TRANSFORM-HF: ToRsemide compArisoN With furoSemide FORManagement of Heart Failure

Study Overview
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Brief Summary
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TRANSFORM-HF is a large-scale, pragmatic, randomized, unblinded clinical effectiveness study comparing torsemide versus furosemide as treatment for heart failure. Approximately 6,000 patients with heart failure will be enrolled. The primary objective of the TRANSFORM-HF study is to compare the treatment strategy of torsemide versus furosemide on clinical outcomes over 12 months in patients with heart failure who are hospitalized.

Detailed Description
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This study will be a randomized, unblinded, two-arm, multi-center clinical trial of patients with heart failure who are hospitalized. Heart failure need not be the reason for hospitalization. Patients will be randomized 1:1 to either oral torsemide OR oral furosemide prior to hospital discharge. Oral dosing of torsemide compared to furosemide will be 1mg:2mg. The specific loop diuretic dose will be at the discretion of the treating physician with the above noted conversion. Trial enrollment occurs before hospital discharge, at the discretion of the healthcare provider. As appropriate, adherence to the randomized medication will be encouraged during the remainder of hospitalization and will continue post-discharge. Patients will receive follow-up per standard care without any additional study-specific visits. Patients will have 30-day, 6-month and 12-month follow-up phone contacts for assessments of vital status, interval hospitalizations, adherence, and quality of life. Central follow-up and collection of hospital discharge summaries via IRB-approved mechanisms. Subsets of patients enrolled early in the study have additional phone contacts beyond 12 months, up to 30 months, at six month intervals, to document vital status.

Official Title
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TRANSFORM-HF: ToRsemide compArisoN With furoSemide FORManagement of Heart Failure

Conditions
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Heart Failure

Intervention / Treatment
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* Drug: Torsemide
* Drug: Furosemide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 one of the following criteria: 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) 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 (with most recent value used to determine eligibility) Plan for a daily outpatient oral loop diuretic regimen upon hospital discharge with anticipated need for long-term loop diuretic use ≥ 18 years of age Signed informed consent Exclusion Criteria: End-stage renal disease requiring renal replacement therapy Inability or unwillingness to comply with the study requirements History of heart transplant or actively listed for heart transplant Implanted left ventricular assist device or implant anticipated <3 months Pregnant or nursing women Malignancy or other non-cardiac condition limiting life expectancy to <12 months Known hypersensitivity to furosemide, torsemide, or related agents

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This study will be a randomized, unblinded, two-arm, multi-center clinical trial of patients with heart failure who are hospitalized. Patients will be randomized 1:1 to either oral torsemide OR oral furosemide prior to hospital discharge.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Torsemide<br>Oral dosing of torsemide compared to furosemide will be 1mg:2-4mg. | Drug: Torsemide<br>* Loop diuretic<br>|
| Active Comparator: Furosemide<br>Oral dosing of torsemide compared to furosemide will be 1mg:2-4mg. For patients receiving loop diuretics other than furosemide, conversion to furosemide equivalents will be as follows: 1 mg oral torsemide = 2-4 mg oral furosemide 1 mg oral or intravenous bumetanide = 40 mg oral furosemide | Drug: Furosemide<br>* Loop diuretic<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality, as measured by follow-up phone call | All-cause mortality over a follow-up period of 12 months; subsets of patients to be evaluated at 6 month intervals to document vital status up to 30 months. | 30 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality or all-cause hospitalization, as measured by follow-up phone call | All-cause mortality or all-cause hospitalization over 12 months | 12 months | 
| Total hospitalizations, as measured by follow-up phone call | Total hospitalizations over 12 months | 12 months | 
| All-cause mortality or all-cause hospitalization, as measured by follow-up phone call | All-cause mortality or all-cause hospitalization over 30 days | 30 days | 
| Health-related quality of life, as measured by follow-up phone call | Health-related quality of life over 12 months | 12 months | 
| Symptoms of depression, as measured by follow-up phone call | Symptoms of depression over 12 months | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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loop diuretic