Heart Failure
Conditions
Brief summary
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.
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, 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.
Interventions
DRUGFurosemide
Standard of care diuretic
DRUGTorsemide
Standard of care diuretic
Sponsors
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants All-cause Mortality, Measured at 1 Year. | 30 days and one year | All-cause mortality as measured by phone calls at 30 days and 1 year |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All-cause Hospitalization | up to one year | At least one hospitalization for any reason up to one year |
| Total Hospitalizations | up to one year | Total number of hospitalizations total number of hospitalizations in one year |
| Change in Weight | up to one year | Change in weight up to one year |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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 | 23 |
| 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 | 24 |
| Total | 47 |
Baseline characteristics
| Characteristic | Torsemide | Total | Furosemide |
|---|---|---|---|
| Age, Continuous | 63.20 years STANDARD_DEVIATION 12.05 | 61.93 years STANDARD_DEVIATION 12.89 | 60.6 years STANDARD_DEVIATION 13.85 |
| Beta blocker | 20 Participants | 43 Participants | 23 Participants |
| Blood urea nitrogen | 23.54 mg/dL STANDARD_DEVIATION 8.59 | 21.43 mg/dL STANDARD_DEVIATION 9.29 | 19.33 mg/dL STANDARD_DEVIATION 9.66 |
| Body Mass Index (BMI) | 34.39 kg/m^2 STANDARD_DEVIATION 9.13 | 34.13 kg/m^2 STANDARD_DEVIATION 8.18 | 33.87 kg/m^2 STANDARD_DEVIATION 7.26 |
| Chronic oral loop diuretic dose in furosemide equivalents (mg) | 40 milligrams furosemide equivalents | 40 milligrams furosemide equivalents | 40 milligrams furosemide equivalents |
| Daily Dose of prescribed heart medications | 25 milligrams | 25 milligrams | 25 milligrams |
| Diastolic blood pressure | 77.20 mmHg STANDARD_DEVIATION 10.1 | 77.31 mmHg STANDARD_DEVIATION 9.35 | 77.43 mmHg STANDARD_DEVIATION 8.72 |
| eGFR < 30 ml/min/1.73 m^2 | 2 Participants | 2 Participants | 0 Participants |
| eGFR < 60 ml/min/1.73 m^2 | 14 Participants | 23 Participants | 9 Participants |
| estimated Glomerular Filtration Rate (eGFR) | 58.84 ml/min/1.73 m^2 STANDARD_DEVIATION 26.38 | 64.06 ml/min/1.73 m^2 STANDARD_DEVIATION 25.16 | 69.51 ml/min/1.73 m^2 STANDARD_DEVIATION 23.13 |
| Heart Failure hospitalization in the past year | 4 Participants | 8 Participants | 4 Participants |
| Heart rate | 70.73 beats per minute STANDARD_DEVIATION 9.31 | 68.80 beats per minute STANDARD_DEVIATION 10.24 | 66.86 beats per minute STANDARD_DEVIATION 10.95 |
| Hemoglobin | 13.59 g/dl STANDARD_DEVIATION 2.41 | 13.09 g/dl STANDARD_DEVIATION 2.32 | 12.58 g/dl STANDARD_DEVIATION 2.16 |
| Hydralazine & Nitrates | 1 Participants | 2 Participants | 1 Participants |
| Hypertension drugs | 14 Participants | 30 Participants | 16 Participants |
| Ischemic cardiomyopathy | 7 Participants | 14 Participants | 7 Participants |
| Left ventricular ejection fraction (LVEF) | 43.40 percentage of blood ejected STANDARD_DEVIATION 17.68 | 41.87 percentage of blood ejected STANDARD_DEVIATION 16.26 | 40.26 percentage of blood ejected STANDARD_DEVIATION 14.94 |
| LVEF < 40% | 9 Participants | 19 Participants | 10 Participants |
| Mineralocorticoid receptor antagonist | 10 Participants | 22 Participants | 12 Participants |
| NT-pro-B-type natriuretic peptide | 1550 pg/ml | 883 pg/ml | 362.5 pg/ml |
| Number of participants with comorbid conditions Diabetes mellitus | 13 Participants | 23 Participants | 10 Participants |
| Number of participants with comorbid conditions History atrial fibrillation/flutter | 8 Participants | 15 Participants | 7 Participants |
| Number of participants with comorbid conditions Hypertension | 8 Participants | 15 Participants | 7 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 13 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) White | 16 Participants | 32 Participants | 16 Participants |
| Region of Enrollment United States | 24 participants | 47 participants | 23 participants |
| Serum bicarbonate | 21.98 mmol/L STANDARD_DEVIATION 3.43 | 21.76 mmol/L STANDARD_DEVIATION 3.12 | 21.53 mmol/L STANDARD_DEVIATION 2.83 |
| Serum chloride | 101.66 mmol/L STANDARD_DEVIATION 2.73 | 102.27 mmol/L STANDARD_DEVIATION 2.78 | 102.88 mmol/L STANDARD_DEVIATION 2.76 |
| Serum creatinine | 1.21 mg/dL STANDARD_DEVIATION 0.35 | 1.16 mg/dL STANDARD_DEVIATION 0.39 | 1.10 mg/dL STANDARD_DEVIATION 0.43 |
| Serum potassium | 4.69 mmol/L STANDARD_DEVIATION 0.53 | 4.59 mmol/L STANDARD_DEVIATION 0.5 | 4.50 mmol/L STANDARD_DEVIATION 0.46 |
| Serum sodium | 139.86 mmol/L STANDARD_DEVIATION 3.19 | 139.82 mmol/L STANDARD_DEVIATION 2.87 | 139.79 mmol/L STANDARD_DEVIATION 2.59 |
| Sex: Female, Male Female | 5 Participants | 13 Participants | 8 Participants |
| Sex: Female, Male Male | 19 Participants | 34 Participants | 15 Participants |
| Sodium-glucose cotransporter-2 inhibitors (SGLT2i) | 12 Participants | 17 Participants | 5 Participants |
| Systolic blood pressure | 127.62 mmHg STANDARD_DEVIATION 17.97 | 128.25 mmHg STANDARD_DEVIATION 16.89 | 128.91 mmHg STANDARD_DEVIATION 16.07 |
| Thiazide | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 1 / 24 |
| other Total, other adverse events | 0 / 23 | 0 / 24 |
| serious Total, serious adverse events | 0 / 23 | 0 / 24 |
Outcome results
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
Time frame: 30 days and one year
Population: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Furosemide | Number of Participants All-cause Mortality, Measured at 1 Year. | 30 days | 0 Participants |
| Furosemide | Number of Participants All-cause Mortality, Measured at 1 Year. | one year | 0 Participants |
| Torsemide | Number of Participants All-cause Mortality, Measured at 1 Year. | 30 days | 0 Participants |
| Torsemide | Number of Participants All-cause Mortality, Measured at 1 Year. | one year | 1 Participants |
Comparison: Mortality at 1 yearp-value: 1t-test, 2 sided
Secondary
All-cause Hospitalization
At least one hospitalization for any reason up to one year
Time frame: up to one year
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Furosemide | All-cause Hospitalization | 6 Participants |
| Torsemide | All-cause Hospitalization | 7 Participants |
p-value: 0.729t-test, 2 sided
Secondary
Change in Weight
Change in weight up to one year
Time frame: up to one year
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Furosemide | Change in Weight | -1.84 kilograms | Standard Deviation 4.9 |
| Torsemide | Change in Weight | -3.04 kilograms | Standard Deviation 10.22 |
p-value: 0.873t-test, 2 sided
Secondary
Total Hospitalizations
Total number of hospitalizations total number of hospitalizations in one year
Time frame: up to one year
Population: 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.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Furosemide | Total Hospitalizations | 0 hospitalizations |
| Torsemide | Total Hospitalizations | 0 hospitalizations |
p-value: 0.65t-test, 2 sided