Bumetanide Injection for Heart Failure

(MsDR Trial)

Overseen By Veena Rao

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Yale University

Must not be taking: Non-loop diuretics

Disqualifiers: Low GFR, Flash pulmonary edema, others

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

Compensation: Varies

Number of Visits: 5

Duration: 9 days

75 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the effects of different doses of bumetanide injections on people with heart failure. Researchers seek to determine how well these doses manage symptoms and improve heart function. Participants must have a clinical diagnosis of heart failure, remain stable without changes in their treatment plan, and not have been hospitalized in the past three months. Those managing heart failure and meeting these criteria might find this trial a good fit.

As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot use non-loop diuretics in the 14 days before the study, except for low-dose aldosterone antagonists like spironolactone or eplerenone at 50 mg or less.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that bumetanide is generally safe to use. The FDA has already approved it to treat swelling from heart, liver, or kidney issues. Studies indicate that bumetanide is effective and safe, even for people with heart failure and chronic kidney disease.

Other research found that bumetanide has a safety level similar to other medications like furosemide, which is a positive sign for its safety in humans. Although this trial is in its early stages (Phase 1), focusing mainly on safety, existing evidence suggests that bumetanide is well-tolerated. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for heart failure?

Researchers are excited about bumetanide injections for heart failure because these injections offer rapid fluid removal compared to the standard oral diuretics like furosemide. Unlike oral medications, bumetanide injections can be more effective for patients with severe fluid retention, as they bypass the digestive system and work directly in the bloodstream. This direct administration not only allows for quicker relief of symptoms but also offers precise dosing, which can be crucial for managing acute heart failure situations. Additionally, the trial explores various dosages, potentially optimizing treatment effectiveness and minimizing side effects.

What evidence suggests that Bumetanide Injection might be an effective treatment for heart failure?

Research has shown that bumetanide can greatly aid people with heart failure by increasing urination, which helps remove excess salt and water from the body. For those with heart failure, it helps control fluid levels, reducing symptoms like swelling and difficulty breathing. Studies comparing bumetanide to other similar drugs suggest it works equally well in eliminating excess fluid. Additionally, bumetanide may be less likely to worsen insulin resistance, which is important for the overall health of heart failure patients. Overall, bumetanide presents a promising option for managing heart failure symptoms. Participants in this trial will receive different dosages of bumetanide to evaluate its effectiveness and safety at varying levels. ^{2 3 5 6 7}

Who Is on the Research Team?

Jeffrey Testani, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for adults over 18 with heart failure who are stable on their current medications and haven't been hospitalized in the last 3 months. They should not have severe kidney issues, be using certain diuretics, or have conditions like restrictive cardiomyopathy. Pregnant or breastfeeding individuals and those unable to follow the study plan are excluded.

Inclusion Criteria

I am older than 18 years.

I am not planning to change my heart failure treatments during the study.

I have been diagnosed with heart failure.

Exclusion Criteria

I have chronic issues with holding urine that would prevent me from doing certain tests.

Your hemoglobin level is less than 8 grams per deciliter.

I haven't taken any water pills except for low-dose spironolactone or eplerenone in the last 2 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Pre-study Diet

Participants follow a study diet provided by the metabolic kitchen to decrease variability in diuretic response

5 days

Treatment

Participants receive randomized doses of bumetanide and undergo bio-specimen collection

9 days

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Bumetanide Injection

Trial Overview

The study tests how well different doses of Bumetanide Injection work in patients with heart failure. It's a controlled experiment where each patient receives multiple doses in random order without knowing which dose they're getting at any time.

How Is the Trial Designed?

Group I: Bumetanide 2.5 mg Active Control 1 Intervention

2.5 mg Randomized to doses 10 mg, 5 mg, 2.5 mg, 1.25 mg

Group II: Bumetanide 1.25 mg Active Control 1 Intervention

1.25 mg Randomized to doses 10 mg, 5 mg, 2.5 mg, 1.25 mg

Group III: Bumetanide 10 mg Active Control 1 Intervention

Randomized to doses 10 mg, 5 mg, 2.5 mg, 1.25 mg

Group IV: Bumetanide 5 mg Active Control 1 Intervention

5 mg Randomized to doses 10 mg, 5 mg, 2.5 mg, 1.25 mg

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

A transvaginal ultrasound-guided injection of botulinum toxin A (BoNT-A) in 12 women significantly improved symptoms of lower urinary tract syndrome, as shown by better scores in the international prostate symptom score (IPSS) and patient perception of bladder condition (PPBC) after the procedure.

The technique was found to be safe, with only one patient experiencing new urge urinary incontinence, and it also reduced the need for clean intermittent catheterization (CIC) in patients requiring it.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Efficacy of Transvaginal Ultrasound-Guided BoNT-A External Sphincter Injection in Female Patients with Underactive Bladder. Tsai, CY., Yeh, YH., Tsai, LH., et al.[2023]

Intranasal injections of a form of prednisolone (Hydeltra(R) TBA) provided significant relief from nasal obstruction in 78% of patients suffering from conditions like seasonal allergic rhinitis and sinusitis-related nasal edema.

The treatment was well-tolerated, with minimal side effects, primarily a small amount of bleeding during injection, allowing for effective local anti-inflammatory action without systemic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intranasal injection of corticosteroids. SIMMONS, MW.[2018]

In a study involving 7605 outpatients with heart failure and reduced left ventricular ejection fraction, a performance improvement intervention led to a significant increase in the use of target doses of β-blockers, improving from 36.1% to 45.9% over 24 months.

The intervention did not result in similar increases for ACE inhibitors/ARBs or aldosterone antagonists, indicating a need for further research to understand barriers to achieving target doses for these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medication dosing in outpatients with heart failure after implementation of a practice-based performance improvement intervention: findings from IMPROVE HF. Gheorghiade, M., Albert, NM., Curtis, AB., et al.[2022]

Drug therapy for heart failure due to left ventricular dysfunction is proven to improve patient prognosis and is both safe and cost-effective, highlighting its importance in treatment plans.

This paper is the first in a series that will focus on the most relevant and applicable evidence regarding drug therapies for chronic heart failure, specifically targeting left ventricular systolic dysfunction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug therapy for chronic heart failure due to left ventricular systolic dysfunction: a scientific review. I. Introduction. Carneiro, AV.[2008]

In a study of 187 women receiving a 100 U injection of onabotulinumtoxinA (BnTA) for urgency urinary incontinence, 10% experienced urinary retention, with 8% having symptomatic retention and 2% having asymptomatic retention.

Women with a history of anti-stress urinary incontinence procedures were more likely to experience urinary retention, indicating that prior surgical interventions may increase the risk of retention after BnTA treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The First Injection: Rates of Urinary Retention in Women With Urgency Incontinence Treated With Intravesical OnabotulinumtoxinA Injection. Squires, NA., Mueller, MG., Lewicky-Gaupp, C., et al.[2021]

Ultrasound-assisted intravesical delivery of botulinum toxin A (BTX-A) using microbubbles significantly reduced bladder hyperactivity in a rat model, demonstrating its potential as a non-injection treatment method.

This method led to increased cleavage of SNAP-25 and reduced release of calcitonin gene-related peptide (CGRP), indicating a mechanism by which BTX-A can effectively alleviate symptoms of overactive bladder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrasound-assisted intravesical botulinum toxin A delivery attenuates acetic acid-induced bladder hyperactivity in rats. Liu, Q., Gao, Y., Cong, H., et al.[2023]

Patients with heart failure and reduced ejection fraction benefit from various medications, including ACE inhibitors, beta blockers, and newer drug classes like angiotensin receptor blocker/neprilysin inhibitors, which have been shown to improve survival rates.

For those hospitalized due to heart failure, implementing disease management programs and telemonitoring can significantly lower the chances of readmission and improve overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Heart Failure Due to Reduced Ejection Fraction: Medical Management. Chavey, WE., Hogikyan, RV., Van Harrison, R., et al.[2017]

In a study of 8399 patients with heart failure, the angiotensin-neprilysin inhibitor LCZ696 was found to significantly reduce the need for intensified treatment and emergency visits for worsening heart failure compared to the angiotensin-converting enzyme inhibitor enalapril.

Patients treated with LCZ696 experienced 23% fewer hospitalizations for heart failure and showed early and sustained improvements in biomarkers indicating heart stress and injury, suggesting it is more effective in preventing clinical deterioration in heart failure patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Angiotensin receptor neprilysin inhibition compared with enalapril on the risk of clinical progression in surviving patients with heart failure. Packer, M., McMurray, JJ., Desai, AS., et al.[2022]

Recent large-scale studies have shown that vasodilators and ACE inhibitors can significantly improve survival rates in patients with congestive heart failure (CHF), highlighting their importance in treatment plans.

Ongoing trials are investigating the effects of these treatments on patients with asymptomatic left ventricular dysfunction, suggesting a potential for early intervention in preventing CHF progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of treatment on survival in congestive heart failure. Pitt, B., Cohn, JN., Francis, GS., et al.[2019]

OnabotulinumtoxinA injections are a safe and effective second-line treatment for adults with refractory overactive bladder, showing improvement in 60%-65% of patients compared to placebo.

The optimal dose of 100 U, approved by the FDA, provides symptom relief for 6 to 12 months, with a low risk of urinary retention at around 6%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

OnabotulinumtoxinA for the treatment of overactive bladder. Cox, L., Cameron, AP.[2023]

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