A Randomized, Two-Period, Two-Arm, Double-Dummy, Crossover Study to Compare Natriuretic Effects of Extended Release Torsemide to Immediate Release Torsemide in Patients With Heart Failure (NEXT-HF)
Trial Snapshot
- Phase
- Phase 4
- Status
- Withdrawn
- Sponsor
- Sarfez Pharmaceuticals, Inc.
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- Urinary sodium excretion measurement
Study Overview
Brief Summary
The primary objective of this study is to learn whether a morning dose of extended-release torsemide enhances renal sodium excretion after lunch (4-8 hours after dosing) compared to immediate-release torsemide.
This is a randomized, double-blind, crossover study in patients with heart failure who are on a stable dose of a loop diuretic.
The primary endpoint will be urinary sodium excretion (4-8 hours after dosing). This will be compared between the extended-release arm and the immediate-release arm to assess the efficacy of prolonged diuretic action. In addition, urinary potassium and creatinine excretion and creatinine clearance will be measured in all urine samples as the safety endpoints.
Detailed Description
Research Plan
Study Design
This is a double-blind, double-dummy, two-period, two-arm, randomized, crossover study.
Initial Study Procedures
Identification of Participants: Patients with a known history of stable heart failure (HF) for at least one month will be identified through healthcare records at clinical site, heart failure clinic, nephrology clinic, and other relevant clinics.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age: 18 years or older.
- •Informed Consent: Willing and able to sign the informed consent form.
- •Stable Chronic HF: A clinical diagnosis of chronic heart failure considered stable by the patient's cardiologist/physician or another experienced clinician for at least one month prior to randomization.
- •Current Diuretic Therapy: Receiving an oral dose of 20 mg to 80 mg daily of furosemide, or 10 mg to 40 mg daily dose of torsemide, or 1 mg to 4 mg daily dose of bumetanide, for about 30 days prior to randomization.
- •Stable HF Medications: No anticipated changes in HF medications during the study period.
- •Female Participants: Premenopausal women of childbearing potential must have a negative pregnancy test prior to study initiation and agree to use effective contraceptive methods throughout the study period.
Exclusion Criteria
- •Other Diuretics: Requirement for a diuretic other than furosemide, bumetanide, or torsemide (except for spironolactone, eplerenone, finerenone, or SGLT2 inhibitors) at randomization or during the study.
- •Recent Cardiovascular Events: Myocardial infarction, stroke, transient ischemic attack, acute kidney injury, or acute HF requiring hospitalization within 30 days prior to randomization.
- •Severe Lung Disease: Severe or symptomatic lung disease or respiratory symptoms distinct from HF.
- •Urinary Issues: History of urinary incontinence, or inability to empty the bladder.
- •Uncontrolled Comorbidities: Uncontrolled diabetes mellitus or hypertension.
- •Renal Dysfunction: Estimated GFR < 30 ml/min/1.72m².
- •Cardiac Conditions: History of flash pulmonary edema or amyloid cardiomyopathy.
- •Breastfeeding: Female participants who are breastfeeding.
- •Recent Participation in Clinical Trials: Participation in another clinical trial within the last three months prior to randomization.
- •Requirements for treatment with a non-steroidal anti-inflammatory drug (except for Aspirin up to 200 mg as PRN daily).
- •Serum potassium concentration <3.5 or >5.5 mmol/L.
Arms & Interventions
Arm 1 IR torsemide
Approximately half of the participants will receive 20 mg IR torsemide followed by 24 mg ER torsemide or 40mg IR torsemide followed by 48 mg ER torsemide (6-10 days each)
Intervention: Extended Release Torsemide Tablets (Drug)
Arm 1 IR torsemide
Approximately half of the participants will receive 20 mg IR torsemide followed by 24 mg ER torsemide or 40mg IR torsemide followed by 48 mg ER torsemide (6-10 days each)
Intervention: Immedate Release Torsemide Tablets (Drug)
ARM 2 ER torsemide
The other half will receive 24 mg ER torsemide followed by 20 mg IR torsemide, or 48 mg ER torsemide followed by 40 mg IR torsemide (6-10 days each)
Intervention: Extended Release Torsemide Tablets (Drug)
ARM 2 ER torsemide
The other half will receive 24 mg ER torsemide followed by 20 mg IR torsemide, or 48 mg ER torsemide followed by 40 mg IR torsemide (6-10 days each)
Intervention: Immedate Release Torsemide Tablets (Drug)
Outcomes
Primary Outcomes
Urinary sodium excretion measurement
Time Frame: 4-8 hours (post-lunch period)
Urinary sodium excretion (mmol) measured after dosing: 4-8 hours (post-lunch period)
Secondary Outcomes
- Urinary sodium excretion(0-4 hours (pre-lunch period) and 8-24 hours (post-lunch period))