Clinical trial NCT03187509: Weight-Based Torsemide Dosing in Subjects With Heart Failure
Official title: Weight-Based Torsemide Dosing vs. Standard Outpatient Management in Subjects With Heart Failure: A Randomized Open-Label Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Heart Failure
Keywords: Torsemide, loop diuretics, weight-based
Lead sponsor: New York City Health and Hospitals Corporation
Sponsor class: OTHER
First posted: 2017-06-15
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will be a randomized open-label pilot study. The purpose of the study is to compare standard of care outpatient heart failure management versus a weight based torsemide regimen. Subjects admitted to the hospital for heart failure exacerbation will be randomized upon discharge to either standard of care outpatient heart failure management or a weight based torsemide regimen. Those subjects randomized to standard of care therapy will be prescribed a daily fixed dose of a loop diuretic at hospital discharge and have a follow-up appointment within one week of discharge. All management decisions including loop diuretic type, dose and frequency will be made at the discretion of the subject's personal physician. Those randomized to an individualized weight based torsemide regimen will be prescribed a dose of torsemide upon hospital discharge based on a prespecified algorithm. These subjects will then undergo physician-subject phone encounters three times a week where the subject's torsemide dose will be modified based on the prespecified algorithm which incorporates current symptoms and weight. Primary end-point will be an unbiased estimate of 30-day all cause readmission rates. Secondary end-points include incidence of acute kidney injury, changes in brain natriuretic peptide levels from baseline and a preliminary estimate of the effect size and feasibility of a weight-based torsemide regimen intervention in order to plan a future larger study.

Detailed description: This study will be an open-label parallel randomized pilot study comparing an individualized weight-based torsemide dosing regimen vs. standard outpatient management in patients with a diagnosis of heart failure.The study will include consenting subjects who are admitted to Jacobi Medical Center with heart failure and were treated with loop diuretic therapy during hospitalization. Prior to discharge, these subjects will be randomized to one of two groups, either an individualized weight-based torsemide regimen group vs. a standard heart failure management group.

After randomization, all subjects will undergo an initial assessment prior to discharge. All subjects will be examined, weighed and assigned a composite congestion score (CCS). CCS is a measurement of current fluid status that has been shown to correlate with clinical outcomes in heart failure patients (19). It assesses a patient's signs and symptoms of congestion, including dyspnea, orthopnea, fatigue, jugular venous distention, rales and peripheral edema. Each category is given a score from 0-3, 0=none, 1=mild,2=moderate and 3=severe. Each subject is given a final composite score for their current volume status.

After discharge, those randomized to standard care will receive standard heart failure care as currently provided in our institution. This routinely includes, but is not limited to, an appointment with their primary care physician within one week of discharge, nutrition consultation, and social work evaluation with support services provided as determined by the social worker. At discharge, all heart failure medication changes including diuretic type, dose and frequency, as well as further management decisions, will be left to the discretion of the subject and the subject's doctors. Those who will be randomized to the individualized weight-based torsemide regimen will be given a standup home scale and torsemide 20mg tabs in a bottle with 100 tablets.

An initial torsemide dose will be assigned based on the patient's GFR and CCS at discharge. These subjects will then have a phone encounter with a physician three times a week where subjects will be instructed to modify the torsemide dose based on their current weight. Patients will be instructed to weigh themselves at the same time of the day, postvoid, prior to eating, prior to the medication dose, and while wearing the same clothing for consistency. The scales should stand on a flat, solid surface rather than carpets unless specifically designed for use in that setting. All phone call encounters and loop diuretic changes will be based on the pre-specified algorithm. These subjects will also receive all the same care and support as a standard subject, including the primary care appointment in one week and other support services, except with instructions to the subject and provider to follow the loop diuretic recommendations from this protocol. Subjects who have been instructed to take more than 80 torsemide 20mg tablets will receive a delivery of 100 additional torsemide 20mg tablets.

All subjects in the study will have follow up visit at week 5 from discharge date. Total diuretic use during the study period will be assessed and current symptoms/quality of life will be evaluated using the Kansas City Cardiomyopathy Questionnaire. The patient will receive a physical examination including a final weight and calculation of composite congestion score. Serum B-type natriuretic peptide (BNP) will be obtained as well as a basic metabolic panel and serum magnesium level to assess for electrolyte disturbances and changes in kidney function. Intervention group subjects will have a count of the remaining number of torsemide tablets in the bottle of torsemide given to them at discharge. Compliance with the algorithm will be assessed by comparing the number of remaining tablets with the number of tablets prescribed during the study. Subjects whose follow-up visit occurs over 45 days after the date of hospital discharge for the enrollment hospitalization shall be deemed to be late for follow-up. Acute kidney injury (AKI) will be defined as an increase in serum creatinine concentration of 0.3 at the five-week follow-up visit compared to the final serum creatinine level measured during hospitalization. Adherence will be measured by comparing the number of tablets in the subject's torsemide supply to the number of expected tablets in the torsemide supply. Adherence will be defined as a tablet count consistent with the subject having taken 88% or more of the expected torsemide tablets

Eligibility criteria: Inclusion Criteria:

1. All subjects with admission diagnosis of heart failure, including heart failure with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF) treated with loop diuretics during hospitalization
2. Must be at least 18 years old at time of enrollment
3. Must have reliable access to a telephone, and be able to speak and understand English or Spanish over a telephone connection

Exclusion Criteria:

1. Any subject who is currently pregnant
2. Any subject with end-stage renal disease requiring hemodialysis
3. Any subject with serum potassium concentration \< 3.5 mEq/L at discharge
4. Any subject with serum magnesium concentration \< 1.4 mg/dL at discharge
5. Any subject with a known history of allergic reaction to loop diuretics
6. Any subject with known severe stenotic valvular heart disease
7. Any subject who requires chronic inotropic pharmacotherapy
8. Any subject undergoing evaluation for cardiac transplantation or left-ventricular assist device
9. Any subject who is not able to provide informed consent

Primary outcomes:
measure: 30-day all-cause readmission rate
timeFrame: 30 days from enrollment
Secondary outcomes:
measure: Effect size of weight based torsemide regimen compared to standard therapy
timeFrame: 30 days from enrollment
measure: Feasibility of a weight based torsemide regimen
timeFrame: 30 days from enrollment
measure: Incidence of acute kidney injury (AKI)
timeFrame: 30 days from enrollment
measure: Comparison of baseline changes of brain natriuretic peptide (BNP) levels
timeFrame: 30 days from enrollment
Other outcomes:
Locations:
city: Bronx
country: United States
facility: Jacobi Medical Cent
state: New York
Study officials:
affiliation: Jacobi Medical Center, Albert Einstein College of Medicine
name: Robert Siegel, MD
role: PRINCIPAL_INVESTIGATOR
References: