Extended vs Immediate Release Torsemide for Heart Failure

(NEXT-HF Trial)

Overseen By Chris Wilcox, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Sarfez Pharmaceuticals, Inc.

Must be taking: Loop diuretics

Must not be taking: Other diuretics

Disqualifiers: Recent cardiovascular events, severe lung disease, uncontrolled diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether taking extended-release torsemide in the morning helps people with heart failure excrete more sodium through urine after lunch compared to the immediate-release version. Participants will try both versions of torsemide, a medication that removes excess fluid, to determine which works better for them. Ideal candidates have stable heart failure and currently take a consistent dose of a loop diuretic (a type of water pill). The study aims to determine if one version of the medication provides longer-lasting fluid and sodium removal. As a Phase 4 trial, this research involves an FDA-approved treatment and seeks to understand its benefits for more patients.

Will I have to stop taking my current medications?

If you are currently taking a loop diuretic like furosemide, bumetanide, or torsemide, you will need to switch to the study medication, torsemide, during the trial. Other medications for heart failure should remain stable, and you should not need to stop them.

What is the safety track record for torsemide?

Research has shown that torsemide, in both regular and long-lasting forms, is generally safe for treating heart failure. Studies have found that torsemide, compared to furosemide (another common diuretic), does not result in more deaths or hospital visits, indicating it is well-tolerated by patients.

For regular torsemide, findings suggest no significant increase in side effects compared to furosemide. Patients taking torsemide experienced similar heart-related and overall health outcomes.

Long-lasting torsemide is also considered safe. Research comparing it to the regular version shows no major differences in safety, meaning the long-lasting form does not cause more side effects than the regular form.

Since this trial is in the post-marketing surveillance phase, torsemide has already received FDA approval for heart failure, indicating that earlier research thoroughly evaluated its safety. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the extended and immediate release forms of torsemide for heart failure because they offer flexibility in drug release and absorption. Unlike standard diuretics, which are often limited to one release type, these forms of torsemide can be tailored to patient needs. Immediate-release (IR) torsemide provides quick relief by rapidly reducing fluid overload, while extended-release (ER) torsemide maintains a steady effect, potentially enhancing patient comfort and adherence. This combination approach aims to improve overall management of heart failure symptoms compared to existing treatments.

What evidence suggests that this trial's treatments could be effective for heart failure?

This trial will compare the immediate-release (IR) and extended-release (ER) forms of torsemide for heart failure. Studies have shown that both forms of torsemide can help people with heart failure. Research indicates that torsemide reduces the risk of hospital stays due to heart failure compared to furosemide, a common water pill. This suggests it may help keep patients out of the hospital. Additionally, torsemide is associated with a slightly lower risk of death. While this trial compares the immediate and extended-release versions, both types have demonstrated benefits in managing heart failure symptoms. ^{2 4 5 6 7}

Who Is on the Research Team?

Salim Shah, PhD, JD

Principal Investigator

Sarfez Pharmaceuticals, Inc.

Are You a Good Fit for This Trial?

This trial is for heart failure patients who are already taking loop diuretics. They should be stable on their current medication and willing to switch to either extended-release or immediate-release Torsemide for the study. Specific inclusion and exclusion criteria details were not provided.

Inclusion Criteria

My heart failure medications will not change during the study.

Informed Consent: Willing and able to sign the informed consent form

I am 18 years old or older.

Exclusion Criteria

I am not taking any NSAIDs except for possibly low-dose Aspirin.

Breastfeeding: Female participants who are breastfeeding

Serum potassium concentration <3.5 or >5.5 mmol/L

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Stabilization

Participants are stabilized on the assigned torsemide formulation

1 week

1 visit (in-person)

Treatment Period 1

Participants receive either IR or ER torsemide for 6-10 days, followed by a test day with urine and blood sample collection

6-10 days

1 visit (in-person)

Washout/Crossover

Participants switch to the alternate torsemide formulation for 6-10 days, followed by a test day with urine and blood sample collection

6-10 days

1 visit (in-person)

Follow-up

Participants resume their pre-enrollment diuretic regimen and continue routine follow-up with their physicians

What Are the Treatments Tested in This Trial?

Interventions

• Torsemide

Trial Overview The study compares two forms of Torsemide: an extended-release version that's supposed to work over a longer period, and an immediate-release version that works quickly. It's a randomized, double-blind crossover trial where participants will try both versions at different times.

How Is the Trial Designed?

Group I: Arm 1 IR torsemide Active Control 2 Interventions

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)

Group II: ARM 2 ER torsemide Active Control 2 Interventions

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)

Who Is Running the Clinical Trial?

Sarfez Pharmaceuticals, Inc.

Lead Sponsor

Trials

6

Recruited

100+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10824237/

Effect of Furosemide Versus Torsemide on Hospitalizations ... In conclusion, patients with HF treated with torsemide have a reduced risk of hospitalizations compared with those treated with furosemide, without any ...

2. ahajournals.org ahajournals.org/doi/10.1161/CIRCULATIONAHA.123.064842

Effect of Torsemide Versus Furosemide on Symptoms and ... Among patients discharged after hospitalization for HF, a strategy of torsemide compared with furosemide did not improve symptoms or quality of life over 12 ...

3. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2800428

Effect of Torsemide vs Furosemide After Discharge on All ... However, prior observational data demonstrated 1-year mortality rates following heart failure hospitalization of more than 30%. A meta-analysis ...

4. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1002/pds.70130

Comparative Effectiveness and Safety of Torsemide Versus ... Compared with furosemide, initiation of torsemide was associated with a slightly lower risk of a composite of all-cause mortality or heart ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0149291899800071

A Pharmacoeconomic assessment of torsemide and ... Outcomes included CHF/cardiovascular (CV)-related medical costs, change in NYHA class, change in sodium retention score, hospitalizations, physician visits, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10765996/

Efficacy and safety of torsemide versus furosemide in heart ... Results from three trials each showed a nonsignificant reduction in the risk of cardiac death (Figure S2).

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06176794

NCT06176794 | Immediate Release Torsemide Versus ... The purpose of this study is to assess whether a morning dose of the extended release torsemide has a better efficacy than the ordinary immediate release ...