Bumetanide Injection for Heart Failure
(MsDR Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Yale University
Must not be taking: Non-loop diuretics
Disqualifiers: Low GFR, Flash pulmonary edema, others
No Placebo Group
Trial Summary
What is the purpose of this trial?
This study will employ a randomized order, double-blind, repeated measures dose ranging design. This design was chosen in order to generate multiple within-subject serial loop diuretic dose response exposures. The overall study schema will include 75 heart failure (HF) patients.
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.
What data supports the effectiveness of the drug Bumetanide Injection for heart failure?
While the specific effectiveness of Bumetanide Injection for heart failure isn't directly addressed, diuretics (drugs that help remove excess fluid from the body) like Bumetanide are commonly used to manage symptoms in heart failure patients. They help reduce fluid buildup, which can ease symptoms such as swelling and shortness of breath.12345
How is Bumetanide Injection unique for treating heart failure?
Bumetanide Injection is unique for treating heart failure because it is a loop diuretic (a type of medication that helps remove excess fluid from the body) administered via injection, which can provide rapid relief from fluid overload compared to oral diuretics. This can be particularly beneficial in acute settings where quick action is needed to reduce symptoms like swelling and shortness of breath.678910
Eligibility Criteria
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.
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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.
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Trial Timeline
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
Treatment Details
Interventions
- Bumetanide Injection (Loop Diuretic)
Trial OverviewThe 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.
Participant Groups
4Treatment groups
Active Control
Group I: Bumetanide 2.5 mgActive Control1 Intervention
2.5 mg Randomized to doses 10 mg, 5 mg, 2.5 mg, 1.25 mg
Group II: Bumetanide 1.25 mgActive Control1 Intervention
1.25 mg Randomized to doses 10 mg, 5 mg, 2.5 mg, 1.25 mg
Group III: Bumetanide 10 mgActive Control1 Intervention
Randomized to doses 10 mg, 5 mg, 2.5 mg, 1.25 mg
Group IV: Bumetanide 5 mgActive Control1 Intervention
5 mg Randomized to doses 10 mg, 5 mg, 2.5 mg, 1.25 mg
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Yale UniversityNew Haven, CT
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Who Is Running the Clinical Trial?
Yale UniversityLead Sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)Collaborator
References
Medication dosing in outpatients with heart failure after implementation of a practice-based performance improvement intervention: findings from IMPROVE HF. [2022]Eligible outpatients with heart failure (HF) and reduced left ventricular ejection fraction (LVEF) frequently do not receive target doses of HF medications. The Registry to Improve the Use of Evidence-Based Heart Failure Therapies in the Outpatient Setting (IMPROVE HF) evaluated the effect of a practice-based performance improvement intervention on treatment of outpatients with LVEF ≤35%. Specific agent and dose were collected at baseline and 24 months for angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs), β-blockers, and aldosterone antagonists. Changes in dosing over time were analyzed for each medication class. Data were available for 7605 patients. At baseline, target dose treatment rates were 36.1%, 20.5%, and 74.4%, respectively. Absolute and relative improvements of 9.8% and 47.7% ( P
Heart Failure Due to Reduced Ejection Fraction: Medical Management. [2017]Heart failure is an increasingly common condition resulting in high rates of morbidity and mortality. For patients who have heart failure and reduced ejection fraction, randomized clinical trials demonstrate consistent mortality benefit from angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, direct-acting vasodilators, beta blockers, and aldosterone antagonists. Additionally, some data show benefits from two new classes of drugs: angiotensin receptor blocker/neprilysin inhibitor and sinus node modulator. Diuretics and digoxin can be used as needed for symptom control. Statins are not recommended solely for treatment of heart failure. Implantable cardioverter-defibrillators and biventricular pacemakers improve mortality and function in selected patients. For patients who have been hospitalized for heart failure, disease management programs and telemonitoring can reduce hospitalizations and mortality.
Angiotensin receptor neprilysin inhibition compared with enalapril on the risk of clinical progression in surviving patients with heart failure. [2022]Clinical trials in heart failure have focused on the improvement in symptoms or decreases in the risk of death and other cardiovascular events. Little is known about the effect of drugs on the risk of clinical deterioration in surviving patients.
The effect of treatment on survival in congestive heart failure. [2019]Congestive heart failure (CHF) is a disorder characterized by a variety of clinical, biochemical, electrophysiological, and hemodynamic abnormalities. During the past two decades, numerous drugs have been employed in the treatment of this complex syndrome, and many agents have been shown to improve symptoms and ventricular function in patients with CHF. Because CHF is associated with a high risk of death, treatment should be directed not only toward the relief of symptoms, but also toward a reduction in mortality. Many variables have been shown to be related to survival; taken individually, however, each is limited in its utility in predicting prognosis. In recent years, large-scale studies with large sample sizes have directly assessed the effects of treatment on mortality in CHF. Results from these trials indicate that vasodilators and angiotensin-converting enzyme (ACE) inhibitors may improve mortality in patients with symptoms of heart failure. Additional trials are now in progress to evaluate the effect of treatment on patients with asymptomatic left ventricular dysfunction.
Drug therapy for chronic heart failure due to left ventricular systolic dysfunction: a scientific review. I. Introduction. [2008]Heart failure is a complex syndrome resulting from cardiac changes, structural or functional, that cause pump failure and consequently diminished cardiac output. Drug therapy improves patients' prognosis and, based on good-quality evidence, is safe and cost-effective. There are several drug classes that can be used in left ventricular dysfunction, so it may be useful to discuss their stratification and prioritization for clinical practice. This is the first of a series of papers that will present and discuss the most valid, important and applicable evidence on drug therapy in chronic heart failure due to left ventricular systolic dysfunction. We will not discuss acute heart failure (or decompensation of chronic heart failure) or non-pharmacologic treatments (implantable cardioverter-defibrillators, cardiac resynchronization therapy, heart transplantation, anti-platelet therapy, etc.).
Intranasal injection of corticosteroids. [2018]Intranasal injections into the inferior turbinates of a slightly form of prednisolone TBA (Hydeltra(R) TBA) into persons with complaint of nasal obstruction gave considerable relief in 78 per cent of cases. Nasal hyperfunction due to seasonal allergic rhinitis, vasomotor rhinitis and secondary nasal edema from sinusitis was the indication for use. No local or general reactions other than a small amount of bleeding at the time of injection was noted. This method allows full utilization of the anti-inflammatory activity of corticosteroids at the local tissue level without producing a systemic effect.
OnabotulinumtoxinA for the treatment of overactive bladder. [2023]OnabotulinumtoxinA injection is a safe and effective treatment for adults with refractory overactive bladder. There is sufficient level 1 evidence to support offering onabotulinumtoxinA injections as a second-line treatment to patients who have failed behavioral therapy and oral medications such as antimuscarinics and β3 agonists. An intradetrusor injection of 100 U of onabotulinumtoxinA is likely the optimal dose to balance risks and benefits, and this is the dose approved by the US Food and Drug Administration. Improvement in urgency urinary incontinence episodes, as well as symptom scores and quality of life, were seen in around 60%-65% of patients, and were significantly improved compared with those on placebo. Most studies have reported a duration of symptom relief ranging from 6 to 12 months, with repeat injections being safe and efficacious. Overall, the risk of urinary retention was around 6% across the study populations.
The First Injection: Rates of Urinary Retention in Women With Urgency Incontinence Treated With Intravesical OnabotulinumtoxinA Injection. [2021]The aim of the study was to describe the rate of symptomatic and asymptomatic urinary retention and catheterization in women undergoing initial intravesical onabotulinumtoxinA (BnTA) injection for urgency urinary incontinence (UUI).
The Efficacy of Transvaginal Ultrasound-Guided BoNT-A External Sphincter Injection in Female Patients with Underactive Bladder. [2023]Owing to the diverse treatment outcomes after a botulinum toxin A (BoNT-A) injection to the external sphincter, this study aimed to develop a new technique: an ultrasound-guided BoNT-A external sphincter injection. This single-center prospective cohort study was conducted at a tertiary medical center in Taichung, Taiwan. From December 2020 to September 2022, 12 women were enrolled. The patients were evaluated for lower urinary tract syndrome using patient perception of bladder condition (PPBC), international prostate symptom score (IPSS), uroflowmetry, post-void residual volume (PVR), cystometry, and external sphincter electromyography. We evaluated the patients the day before surgery and 1 week after the BoNT-A injection. For the patients requiring self-catheterization, we recorded the number of times they required clean intermittent catheterization (CIC) per day before the procedure and 1 month after the procedure. The IPSS, PPBC, and PVR were significantly better after the transvaginal ultrasound-guided BoNT-A external sphincter injection. The number of times the patients required daily CIC was also reduced after the injection. Only one patient developed de novo urge urinary incontinence. Our results demonstrated that a transvaginal ultrasound-guided BoNT-A injection was efficacious and safe in the treatment of underactive bladder.
Ultrasound-assisted intravesical botulinum toxin A delivery attenuates acetic acid-induced bladder hyperactivity in rats. [2023]Background: Intradetrusor injection of botulinum toxin A (BTX-A) is an effective treatment for overactive bladder (OAB). However, the occurrence of adverse events associated with BTX-A injection therapy hinders its acceptance among patients and its clinical promotion. Intravesical instillation of BTX-A offers a promising alternative to injection therapy for treating OAB. Nevertheless, due to the presence of the bladder permeability barrier (BPB) and the high molecular weight of BTX-A, direct instillation is unable to penetrate the bladder urothelium. Purpose: This study aims to investigate the safety and feasibility of ultrasound-assisted intravesical delivery of BTX-A and its potential benefits in a rat model of bladder hyperactivity induced by acetic acid instillation. Methods: Hengli BTX-A and microbubbles (MB) were mixed and prepared as a novel complex. The size distribution and zeta potentials of the complex were measured. On day 1, rats' bladders were instilled with 1 mL of saline, BTX-A (20 U in 1 mL), MB, or MB-BTX-A (20 U in 1 mL) complex with or without ultrasound (US) exposure (1 MHz, 1.5 W/cm2, 50% duty cycle, sonication for 10 s with a 10-s pause for a total of 10 min). The instillations were maintained for 30 min. After 7 days, cystometry was performed by filling the bladder with saline and 0.3% acetic acid (AA). Bladders were collected, weighed, and processed for immunoblotting, enzyme-linked immunosorbent assay (ELISA), histologic, and immunofluorescence analyses. Expression and distribution of SNAP-25 and SNAP-23 were assessed using Western blot and immunofluorescence. Calcitonin gene-related peptide (CGRP) in the bladder was detected using ELISA. Results: Intercontraction intervals (ICI) decreased by 72.99%, 76.16%, and 73.96% in rats pretreated with saline, BTX-A, and US + MB, respectively. However, rats treated with US + MB + BTX-A showed a significantly reduced response to AA instillation (57.31% decrease in ICI) without affecting amplitude, baseline pressure, or threshold pressure. Rats treated with US + MB + BTX-A exhibited increased cleavage of SNAP-25 and CGRP expression compared to the control group. Conclusion: Ultrasound-assisted intravesical delivery of BTX-A, with the assistance of MB cavitation, led to cleavage of SNAP-25, inhibition of calcitonin gene-related peptide release from afferent nerve terminals, and amelioration of acetic acid-induced bladder hyperactivity. These results support ultrasound-assisted intravesical delivery as an efficient non-injection method for administering BTX-A.