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.
Is Bumetanide Injection a promising drug for heart failure?The provided research articles do not contain information about Bumetanide Injection or its effectiveness for heart failure, so we cannot determine if it is a promising drug for this condition based on the given data.610131415
What data supports the idea that Bumetanide Injection for Heart Failure is an effective treatment?The available research does not provide specific data on the effectiveness of Bumetanide Injection for Heart Failure. Instead, it highlights other drugs like angiotensin-converting enzyme inhibitors and beta blockers, which have shown benefits in reducing mortality and improving symptoms in heart failure patients. Bumetanide, a diuretic, is generally used to manage symptoms by reducing fluid buildup, but the research does not specifically mention its impact on survival or long-term outcomes compared to these other treatments.2781112
What safety data exists for Bumetanide Injection in heart failure treatment?The provided research does not contain safety data for Bumetanide Injection in heart failure treatment. The studies focus on the safety and efficacy of flecainide and encainide, which are antiarrhythmic agents, not Bumetanide. Therefore, no relevant safety data for Bumetanide Injection is available in the given research.13459
Do I have to stop taking my current medications for the trial?The trial does not specify if you need to stop all current medications, but you cannot use non-loop diuretics in the last 14 days before the trial, except for low-dose aldosterone antagonists like spironolactone or eplerenone (≤50 mg).
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.
I haven't been hospitalized unexpectedly in the last 3 months.
Exclusion Criteria
I have chronic issues with holding urine that would prevent me from doing certain tests.
I have been hospitalized for sudden lung swelling needing breathing support, or have a rare heart condition affecting my heart's volume.
My kidney function is very low or I am on dialysis.
Treatment Details
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.
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
Short- and long-term efficacy and safety of flecainide acetate for supraventricular arrhythmias. [2019]This report summarizes efficacy and safety data on the use of flecainide acetate for supraventricular arrhythmias. For this purpose, 60 original articles were identified by a literature search representing data from 1,835 treatment courses. In 18 trials, flecainide was administered intravenously; in 19, orally; and in 23, both forms of therapy were applied. There were 5 placebo-controlled and 12 comparative studies, whereas data from uncontrolled studies were represented in 43 articles. Short-term flecainide administration terminated atrial fibrillation in 65% of attempts and terminated atrial flutter in 28%. The drug was effective during long-term therapy for atrial fibrillation in 49% of patients, with similar efficacy rates in 11 comparative trials and in 16 uncontrolled studies. In randomized, placebo-controlled studies in patients with paroxysmal atrial fibrillation, flecainide was shown to reduce significantly the number of attacks, to prolong the time between attacks, and to improve quality of life. In patients with atrioventricular (AV) reciprocating tachycardias, acute drug administration was successful in 72%; 83% of patients with AV nodal reentrant tachycardias and 74% exhibiting arrhythmias associated with the Wolff-Parkinson-White syndrome responded acutely. During long-term therapy, efficacy rates were 70%, 78%, and 69%, respectively. Ectopic atrial tachycardia responded in 86% and 95% of patients treated with flecainide acutely or chronically. Data concerning drug-related side effects were available for 1,794 of 1,835 treatment courses (98%). Overall, 352 of 1,794 patients (20%) reported at least one non-cardiac or cardiac adverse experience.(ABSTRACT TRUNCATED AT 250 WORDS)
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.
Safety considerations and dosing guidelines for encainide in supraventricular arrhythmias. [2019]The safety issues relevant to treatment with encainide in patients with supraventricular arrhythmia were reviewed based on 349 patients enrolled in clinical trials in the United States and Europe. Although 20% of patients had a history of congestive heart failure, cardiomegaly, or cardiomyopathy at entry, there was no case of new or worsened heart failure. There were 5 cases (1.4%) of proarrhythmia in adults, reflecting a worsening of the arrhythmia being treated or of a coexisting ventricular arrhythmia. The profile of drug-related adverse effects was comparable to that previously reported, causing discontinuance in 6% of patients. The effects most often seen were dizziness, visual disturbance, headache, nausea and vertigo. Only 1 patient had clinically significant abnormal laboratory values, possibly reflecting hepatocellular injury in conjunction with viral hepatitis. Most responders received a daily dose of 75 to 200 mg/day, generally given in 3 divided doses. Encainide has a very favorable safety profile for use in the treatment of supraventricular arrhythmias.
Classification by type of ventricular arrhythmia predicts frequency of adverse cardiac events from flecainide. [2019]Antiarrhythmic therapy is known to be associated with a significant risk of adverse cardiac reactions, including a proarrhythmic response. This study assessed in 1,330 patients followed up for 292 +/- 393 days the predictive value for cardiovascular safety of a system by which patients were classified according to ventricular arrhythmias on entry, presence or absence of organic heart disease and drug dose for flecainide acetate. Baseline arrhythmia subgroups included patients with premature ventricular complexes only, nonsustained ventricular tachycardia, and sustained ventricular tachycardia. Proarrhythmic events occurred in 6.8% of patients overall and were serious in 2.3% and lethal in 1.0%. However, proarrhythmia was highly dependent on arrhythmia class on entry: serious nonlethal proarrhythmic events occurred in 6.6% of patients with sustained ventricular tachycardia, only 0.9% with nonsustained ventricular tachycardia and 0% with premature ventricular complexes (p less than 0.01). Proarrhythmic death occurred in 3.1% of patients with sustained ventricular tachycardia, 0.2% with nonsustained ventricular tachycardia and 0% with premature ventricular complexes only (p less than 0.01). Proarrhythmia was also influenced by the presence of structural heart disease: serious nonlethal proarrhythmia occurred in 2.6% of patients with versus 0.4% of those without organic heart disease, and death occurred in 1.2 versus 0%, respectively. These adverse events were also dependent on dosing regimen. Flecainide caused premature discontinuation due to new or worsened heart failure in 1.4% of patients, all with underlying organic heart disease; however, heart failure was not clearly related to dose or type of arrhythmia. Symptomatic conduction disturbances occurred in 2.2%, and were predicted by preexistent sinus node disease but not by other baseline features.(ABSTRACT TRUNCATED AT 250 WORDS)
Extracardiac adverse effects of flecainide. [2019]The results of a well-controlled multicenter shortterm safety and efficacy study, supported by results from several long-term studies, indicate that therapeutic doses of flecainide are well tolerated by most patients. The most frequently reported extracardiac adverse experiences were dizziness (30%) and visual disturbances (28%), often occurring in tandem. Headache, nausea, dyspnea and chest pain occurred at incidences of 6 to 9%; other adverse experiences occurred at incidences of greater than or equal to 5%. Because of study design, it is likely that these figures are overestimates; they include all reports, whether or not they were caused by flecainide. Extracardiac adverse experiences were given as reasons contributing to discontinuation of therapy in 10% of patients in the short-term and 6% of patients in the long-term studies. In most cases the inability to tolerate flecainide became evident early in therapy. No new adverse experiences indicative of any chronic toxic effect of flecainide were reported during the long-term studies. Side effects tended to be intermittent and to decrease over time.
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.
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.).
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
Safety of flecainide. [2021]Flecainide is a class Ic antiarrhythmic agent that has an important role as part of rhythm control strategies in patients with atrial fibrillation (AF). Early clinical data on the use of flecainide showed an increase in arrhythmias and mortality compared with placebo in patients with a previous myocardial infarction and asymptomatic or mildly symptomatic ventricular arrhythmias. These findings only apply to a specific group of patients with left ventricular dysfunction and ischaemic heart disease, but had a negative impact on the use of class Ic antiarrhythmics across all indications and patient groups. The aim of this review was to evaluate the available safety data for flecainide in the literature and to assess its current use in patients with AF. Current European guidelines now recommend the use of flecainide in carefully selected groups of patients with AF who do not have structural heart disease. This includes for the cardioversion of recent-onset AF, pretreatment prior to direct current cardioversion, out-of-hospital acute oral therapy ('pill-in-the-pocket' approach) and for the ongoing maintenance of sinus rhythm. Potential cardiac adverse effects of flecainide include proarrhythmia, conduction abnormalities and negative inotropic effects. Dizziness is the most frequent non-cardiac side effect, followed by blurred vision and difficulty focusing; these are almost all mild, transient and tolerable. Data from recent clinical trials in patients with supraventricular arrhythmias suggest that flecainide has a good tolerability profile in groups of appropriately selected patients. Caution is required when using flecainide in patients with renal dysfunction, and there are a number of drug interactions, but these are well documented and manageable. Overall, flecainide is a good choice for the pharmacological management of AF. It has a good safety record and low incidence of adverse effects, rare end-organ toxicity and a low risk of ventricular proarrhythmia. To ensure that the benefits of treatment outweigh any potential risks, careful patient selection and monitoring is required.
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.
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.
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.
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.