Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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, NCT03296813.
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, NCT03296813) a mechanistic sub-study of this study and TRANSFORMHF.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Furosemide | Active Comparator | Furosemide, oral, dosage and frequency determined by treating physician or provider. 1 mg torsemide to 2-4 mg oral furosemide |
|
| Torsemide | Active Comparator | Torsemide, oral, dosage and frequency determined by treating physician or provider. 1 mg torsemide to 2-4 mg oral furosemide |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Furosemide | Drug | Standard of care diuretic |
| |
| Torsemide |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants All-cause Mortality, Measured at 1 Year. | All-cause mortality as measured by phone calls at 30 days and 1 year | 30 days and one year |
| Measure | Description | Time Frame |
|---|---|---|
| All-cause Hospitalization | At least one hospitalization for any reason up to one year | up to one year |
| Total Hospitalizations | Total number of hospitalizations total number of hospitalizations in one year |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Yale University | New Haven | Connecticut | 06510 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39196651 | Derived | Rao VS, Cox ZL, Ivey-Miranda JB, Neville D, Balkcom N, Moreno-Villagomez J, Ramos-Mastache D, Maulion C, Bellumkonda L, Tang WHW, Collins SP, Velazquez EJ, Mentz RJ, Wilson FP, Turner JM, Wilcox CS, Ellison DH, Fang JC, Testani JM. Mechanistic Differences between Torsemide and Furosemide. J Am Soc Nephrol. 2025 Jan 1;36(1):99-107. doi: 10.1681/ASN.0000000000000481. Epub 2024 Aug 28. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Furosemide | Furosemide, oral, dosage and frequency determined by treating physician or provider. 1 mg torsemide to 2-4 mg oral furosemide Furosemide: Standard of care diuretic |
| FG001 | Torsemide | Torsemide, oral, dosage and frequency determined by treating physician or provider. 1 mg torsemide to 2-4 mg oral furosemide Torsemide: Standard of care diuretic |
| Title | Milestones | Reasons Not Completed | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Furosemide | Furosemide, oral, dosage and frequency determined by treating physician or provider. 1 mg torsemide to 2-4 mg oral furosemide Furosemide: Standard of care diuretic |
| BG001 | Torsemide |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants All-cause Mortality, Measured at 1 Year. | All-cause mortality as measured by phone calls at 30 days and 1 year | Data presented here is from Yale site only. Only data from the Yale site was collected and analyzed. Data from other site could not be collected. | Posted | Count of Participants | Participants | 30 days and one year |
|
one year
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Furosemide | Furosemide, oral, dosage and frequency determined by treating physician or provider. 1 mg torsemide to 2-4 mg oral furosemide Furosemide: Standard of care diuretic |
Not provided
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jeffrey Testani, MD, MTR Associate Professor of Medicine | Yale School of Medicine | (203) 785-7191 | jeffrey.testani@yale.edu |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 23, 2021 | Jun 27, 2024 | Prot_SAP_000.pdf |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D006333 | Heart Failure |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D005665 | Furosemide |
| D000077786 | Torsemide |
| ID | Term |
|---|---|
| D013424 | Sulfanilamides |
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Drug |
Standard of care diuretic |
|
| up to one year |
| Change in Weight | Change in weight up to one year | up to one year |
Torsemide, oral, dosage and frequency determined by treating physician or provider.
1 mg torsemide to 2-4 mg oral furosemide
Torsemide: Standard of care diuretic
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Body Mass Index (BMI) | Mean | Standard Deviation | kg/m^2 |
|
| Left ventricular ejection fraction (LVEF) | Mean | Standard Deviation | percentage of blood ejected |
|
| LVEF < 40% | Number of participants with LVEF less than 40% | Count of Participants | Participants |
|
| Ischemic cardiomyopathy | Number of participants with Ischemic cardiomyopathy | Count of Participants | Participants |
|
| Heart Failure hospitalization in the past year | Count of Participants | Participants |
|
| Number of participants with comorbid conditions | Count of Participants | Participants |
|
| Systolic blood pressure | Mean | Standard Deviation | mmHg |
|
| Diastolic blood pressure | Mean | Standard Deviation | mmHg |
|
| Heart rate | Mean | Standard Deviation | beats per minute |
|
| Hypertension drugs | Number of participants on Angiotensin-converting enzyme inhibitors (ACEi), Angiotensin II receptor blockers (ARB) or angiotensin receptor/neprilysin inhibitor (ARNI). | Count of Participants | Participants |
|
| Beta blocker | Count of Participants | Participants |
|
| Mineralocorticoid receptor antagonist | Count of Participants | Participants |
|
| Daily Dose of prescribed heart medications | Median | Full Range | milligrams |
|
| Sodium-glucose cotransporter-2 inhibitors (SGLT2i) | Count of Participants | Participants |
|
| Hydralazine & Nitrates | Count of Participants | Participants |
|
| Chronic oral loop diuretic dose in furosemide equivalents (mg) | Mean | Full Range | milligrams furosemide equivalents |
|
| Thiazide | Count of Participants | Participants |
|
| Serum sodium | Mean | Standard Deviation | mmol/L |
|
| Serum chloride | Mean | Standard Deviation | mmol/L |
|
| Serum potassium | Mean | Standard Deviation | mmol/L |
|
| Serum bicarbonate | Mean | Standard Deviation | mmol/L |
|
| Serum creatinine | Mean | Standard Deviation | mg/dL |
|
| Blood urea nitrogen | Mean | Standard Deviation | mg/dL |
|
| estimated Glomerular Filtration Rate (eGFR) | Mean | Standard Deviation | ml/min/1.73 m^2 |
|
| eGFR < 60 ml/min/1.73 m^2 | Number of participants with eGFR less than 60 ml/min/1.73 m2 | Count of Participants | Participants |
|
| eGFR < 30 ml/min/1.73 m^2 | Measure Description: Number of participants with eGFR less than 30 ml/min/1.73 m2 | Count of Participants | Participants |
|
| NT-pro-B-type natriuretic peptide | Mean | Full Range | pg/ml |
|
| Hemoglobin | Mean | Standard Deviation | g/dl |
|
|
|
|
| Secondary | All-cause Hospitalization | At least one hospitalization for any reason up to one year | Data presented here is from Yale site only. Only data from the Yale site was collected and analyzed. Data from other site could not be collected. | Posted | Count of Participants | Participants | up to one year |
|
|
|
|
| Secondary | Total Hospitalizations | Total number of hospitalizations total number of hospitalizations in one year | Data presented here is from Yale site only. Only data from the Yale site was collected and analyzed. Data from other site could not be collected. | Posted | Mean | Full Range | hospitalizations | up to one year |
|
|
|
|
| Secondary | Change in Weight | Change in weight up to one year | Data presented here is from Yale site only. Only data from the Yale site was collected and analyzed. Data from other site could not be collected. | Posted | Mean | Standard Deviation | kilograms | up to one year |
|
|
|
|
| 0 |
| 23 |
| 0 |
| 23 |
| 0 |
| 23 |
| EG001 | Torsemide | Torsemide, oral, dosage and frequency determined by treating physician or provider. 1 mg torsemide to 2-4 mg oral furosemide Torsemide: Standard of care diuretic | 1 | 24 | 0 | 24 | 0 | 24 |
Not provided
Not provided
Not provided
| D000814 |
| Aniline Compounds |
| D000588 | Amines |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |