mirabegron and Spinal-Cord-Injuries

Systematic review.. To evaluate the efficacy and safety of mirabegron in patients with neurogenic detrusor overactivity due to SCI or MS.. A comprehensive search of the Pubmed, Cochrane, Scopus, and Embase databases was performed. Studies evaluating adult patients with neurogenic detrusor overactivity due to SCI or MS were analyzed according to clinical and urodynamic outcome parameters.. A total of 488 patients were included in 11 studies, with sample sizes ranging from 15 to 91. The duration of the treatments varied from 4 weeks to 12 months. Mirabegron was used as a secondline treatment after anticholinergics in most of the studies. While clinical outcome parameters are used in studies involving only MS patients, urodynamic outcome parameters are also used in studies involving patients with SCI. The efficacy of mirabegron was found not to be different than anticholinergics when compared in MS patients. Comprehensive urodynamic evaluation was performed in 2 randomized, double-blind, placebo-controlled studies and no satisfactory results were obtained compared to placebo. In retrospective studies there were some significant improvements in P. Although mirabegron demonstrates similar clinical efficacy to anticholinergics in MS patients, its effect on urodynamic parameters in patients with SCI cannot be considered satisfactory. It has a good safety profile with mild cardiovascular side effects.

Topics: Acetanilides; Adult; Cholinergic Antagonists; Humans; Multiple Sclerosis; Randomized Controlled Trials as Topic; Retrospective Studies; Spinal Cord Injuries; Thiazoles; Treatment Outcome; Urinary Bladder, Neurogenic; Urinary Bladder, Overactive; Urodynamics

Patients with spinal cord injury (SCI) present with a wide range and variety of urologic manifestations, depending upon the level of injury. Historically, patients with spinal cord injury experienced significant mortality related to renal failure. Greater knowledge of the pathophysiology of SCI, however, has contributed to a reduction in mortality. It is essential to perform a thorough initial evaluation and regular follow-up of these patients to achieve the primary goal of preservation of renal function, with the secondary goal of optimizing the patient's quality of life.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Botulinum Toxins, Type A; Catheters, Indwelling; Humans; Muscarinic Antagonists; Neuromuscular Agents; Plastic Surgery Procedures; Spinal Cord Injuries; Thiazoles; Urethra; Urinary Bladder; Urinary Bladder, Neurogenic; Urinary Catheterization; Urinary Diversion; Urodynamics

To analyze cardiovascular safety of mirabegron in patients with spinal cord injury (SCI)- and multiple sclerosis (MS)-induced neurogenic detrusor overactivity (NDO) in a prospective, randomized, double-blind, placebo-controlled study.. Seventy-eight patients were enrolled into the study, and 66 of them were included into the final analysis. In 49 (74.2%), NDO developed due to suprasacral SCI, 17 (25.8%) suffered from NDO due to MS. Eleven patients were previously treated for hypertension and one for arrhythmia. All study participants received placebo for 2 weeks run-in period. Subsequently, eligible subjects were randomized for 4 weeks of active treatment with mirabegron 50 mg once daily (Group A; n = 32) or placebo (Group B; n = 34). Data from resting electrocardiography (ECG), 24-h ECG and blood pressure monitoring, and echocardiographic examination, were used for cardiovascular safety assessment. All reported variables were evaluated at time of randomization and at the end of the study. Longitudinal changes of variables within the groups and differences between the groups were assessed using nonparametric Kruskal-Wallis test, and p ≤ 0.05 was considered statistically significant.. No statistically significant longitudinal changes were found in safety variables, except for prolongation of QT interval in placebo group (p = 0.0328) recorded by resting ECG. No significant difference between the Groups A and B, in any of the variables, was observed. A single cardiovascular study drug-related adverse event was recorded in a patient with cervical SCI (3.13%).. Our results suggest that mirabegron can be safely used in the treatment of patients with SCI- and MS-induced NDO.

Topics: Acetanilides; Adolescent; Adrenergic beta-3 Receptor Agonists; Adult; Aged; Cardiovascular Diseases; Double-Blind Method; Female; Humans; Male; Middle Aged; Multiple Sclerosis; Prospective Studies; Spinal Cord Injuries; Thiazoles; Urinary Bladder, Overactive; Young Adult

To determine the effectiveness of mirabegron in patients with neurogenic lower urinary tract dysfunction.. Randomized, double-blind, placebo-controlled study. Canadian patients with spinal cord injury (SCI) or multiple sclerosis (MS) with urinary symptoms and incontinence were recruited. Patients were randomized to mirabegron 25 mg (or an identical placebo) for 2 weeks at which point a dose escalation to mirabegron 50 mg (or an identical placebo) was maintained for 8 weeks. Urodynamics were performed before and after treatment. The primary outcome measure was maximum cystometric capacity (MCC). Intention to treat analysis and ANCOVA models (with adjustment for baseline values) were used and marginal means (MM) are reported; P-value <0.05 was considered significant.. Among patients with SCI or MS, we demonstrated non-significant trends towards improvement in some urodynamic parameters with mirabegron 50 mg compared to placebo, and a significantly lower neurogenic bladder symptom burden.

Topics: Acetanilides; Adult; Aged; Canada; Double-Blind Method; Female; Humans; Male; Middle Aged; Multiple Sclerosis; Pilot Projects; Spinal Cord Injuries; Thiazoles; Treatment Outcome; Urinary Bladder, Neurogenic; Urinary Bladder, Overactive; Urinary Incontinence; Urodynamics

To assess the clinical, urodynamic efficacy, and safety of mirabegron in patients with neurogenic detrusor overactivity (NDO) consequent to traumatic spinal cord injury (SCI).. This prospective cohort study was performed between January 2018 and July 2019 and included adult patients with stable traumatic suprasacral SCI, performing clean intermittent catheterization (CIC), and demonstrating NDO on urodynamic study (UDS). A 3-day bladder diary was made at the baseline after which all patients were started on Mirabegron 50 mg. They were followed up at 6 weeks with a repeat bladder diary and UDS which were compared with those at the baseline.. A total of 30 patients (4 females, 26 males, mean age: 30.07 years) were included. After 6 weeks of treatment, 5 out of the 29 incontinent patients became completely dry. The mean frequency of CIC decreased from 6.63 at the baseline to 5.37 at 6 weeks (p = .002), the mean CIC volume increased from 275 ml to 341 ml (p = .0002), the mean number of incontinence episodes in between CIC reduced from 3.97 to 2.27 (p < .0001) and time from CIC to leakage increased from 1.73 h to 2.75 h (p < .0001). The mean cystometric capacity increased from 348 ml to 406 ml (p = .008) and the maximum amplitude of NDO decreased from 54 cm H. Mirabegron is efficacious and safe in patients with NDO consequent to traumatic SCI.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Adult; Female; Humans; Male; Prospective Studies; Spinal Cord Injuries; Thiazoles; Urinary Bladder, Overactive

To evaluate whether the long-term usage of mirabegron, which was reported to have potential side effects on male reproductive organs in animal studies, was harmful to spermatogenesis in human testis.. Thirty consecutive patients with spinal cord injury (20-48 years old) who performed clean intermittent catheterization were involved in this study. Ten patients were treated with mirabegron (50 mg/d) for more than 2 years and refrained from using an antimuscarinic agent due to the side effects of constipation and dry mouth. Twenty patients were treated with neither anticholinergic agents nor mirabegron. All underwent conventional testicular sperm extraction. The sperm recovery rate and histopathologic findings of the retrieved testicular tissue were compared between both groups.. We found no difference in the sperm recovery rate (P = .083) between both groups. Spinal cord injury patients treated with mirabegron had better spermatogenesis than those not treated with mirabegron (P < .05).. From these data, we conclude that the therapeutic dose of mirabegron had no harmful effect on spermatogenesis in spinal cord injury patients of reproductive age.

Topics: Acetanilides; Adult; Animals; Humans; Male; Middle Aged; Spermatogenesis; Spinal Cord Injuries; Thiazoles; Young Adult

Pre-post intervention.. 1. To test whether replacement of oral anticholinergic (AC) agents with mirabegron for neurogenic lower urinary tract dysfunction (NLUTD) yields improved cognitive function in older persons with spinal cord injury (SCI). 2. To test whether mirabegron is safe and as efficacious as AC.. USA.. Pilot study: Twenty older (>60 y/o) persons with SCI taking chronic (>6 months) AC medication for NLUTD were enrolled. All participants were first studied on AC at baseline then switched to mirabegron for 6 months. Primary outcomes were cognitive tests of (1) executive function (TEXAS, SDMT); (2) attention (SCWT); and (3) memory (SLUMS and WMS-IV Story A/B). Secondary outcomes assessed efficacy and safety including Neurogenic Bladder Symptom Score (NBSS), bladder diary, neurogenic bowel dysfunction (NBD) survey, heart rate (HR), electrocardiogram (EKG), and mean arterial pressure (MAP).. When switching from AC to mirabegron for NLUTD, older persons with SCI exhibited statistically significant improvements in immediate Story A recall (p = 0.01), delayed story A and B recall (p = 0.01, 0.004), and in TEXAS (p = 0.04). Three subscores within NBSS significantly improved (p = 0.001) and the frequency of incontinence decreased (p = 0.03) on mirabegron. NBD, HR, MAP, and EKGs were unchanged.. Older persons with SCI on AC for NLUTD demonstrated improved short-term and delayed memory (WMS-IV Story A/B) as well as executive function (TEXAS) when switched to mirabegron. Efficacy of mirabegron for NLUTD symptoms was superior to AC with no adverse effects on bowel or cardiovascular function.. Claude D. Pepper Older Americans Independence Center.

Topics: Acetanilides; Aged; Aged, 80 and over; Cholinergic Antagonists; Cognition; Humans; Pilot Projects; Spinal Cord Injuries; Thiazoles; Urinary Bladder, Overactive

The effects of solifenacin and mirabegron on vesical and urethral function were compared in rats with or without spinal cord injury (SCI). Isovolumetric cystometry and urethral pressure recording were initially performed in intact rats. Then, the bladder neck was ligated under urethane anesthesia, after which a catheter was inserted through the bladder dome for isovolumetric cystometry and another catheter was inserted into the urethra to measure urethral pressure. Solifenacin (0.03-3 mg/kg) or mirabegron (0.03-3 mg/kg) was injected intravenously, and bladder and urethral activity were recorded. To create rats with SCI, the spinal cord was transected at the lower thoracic level under isoflurane anesthesia. After 2 weeks, a catheter was inserted through the bladder dome for single cystometry and bladder activity was recorded without anesthesia following intravenous injection of solifenacin or mirabegron. Isovolumetric cystometry revealed a larger decrease in maximum bladder contraction pressure after injection of solifenacin, whereas prolongation of the interval between bladder contractions was greater with mirabegron. In SCI rats, single cystometry showed that solifenacin and mirabegron both increased bladder volume at the first non-voiding bladder contraction and decreased the maximum bladder contraction pressure. Mirabegron also increased the voided volume and decreased the percentage residual volume without altering bladder capacity. Solifenacin and mirabegron both inhibited bladder contractility, and mirabegron possibly also induced urethral relaxation. Mirabegron may be suitable for patients with overactive bladder and residual urine.

Topics: Acetanilides; Animals; Disease Models, Animal; Female; Rats; Rats, Sprague-Dawley; Solifenacin Succinate; Spinal Cord Injuries; Thiazoles; Urethra; Urinary Bladder; Urological Agents

To investigate the effects of combined therapy with an anticholinergic agent and a β3-adrenoceptor agonist on bladder dysfunction and proliferation-related molecule expression in rats with spinal cord injury (SCI).. The spinal cord was transected at the level of T8-9 in female Sprague-Dawley rats, which were divided into four groups; A: Vehicle, B: 10 mg/kg/day of oxybutynin, C: 10 mg/kg/day of mirabegron, and D: combined administration of oxybutynin and mirabegron. Drugs were administered by oral gavage from 2 to 4 weeks after spinal cord transection. We evaluated urodynamic parameters and bladder tissue remodeling factors.. Non-voiding contractions (NVCs) during the storage phase of cystometrograms tended to be decreased in all three treated groups with a significant reduction in group D versus A. Bladder compliance was improved, and intercontraction intervals, voided volume and bladder capacity were increased in group D. In all three treated groups (B-D), the expression of HIF1-α and TGF-β1 was decreased compared to group A. The expression of collagen-III and bFGF was decreased in groups B and D. The total bladder elastin level was increased in group D.. The combination therapy of an anticholinergic agent and a β3-adrenoceptor agonist elevated the bladder elastin level, reduced NVCs, and increased bladder compliance more effectively than the monotherapy in SCI rats. Thus, the combination therapy could be effective for the treatment of neurogenic bladder dysfunction including bladder remodeling. Neurourol. Urodynam. 36:1039-1045, 2017. © 2016 Wiley Periodicals, Inc.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Animals; Disease Models, Animal; Drug Therapy, Combination; Female; Mandelic Acids; Muscarinic Antagonists; Rats; Rats, Sprague-Dawley; Spinal Cord Injuries; Thiazoles; Urinary Bladder; Urinary Bladder, Neurogenic; Urination; Urodynamics; Urological Agents

It is a retrospective chart analysis.. In patients with neurogenic lower urinary tract dysfunction (NLUTD) due to spinal cord injury (SCI), neurogenic detrusor overactivity (NDO) can cause both deterioration of the upper urinary tract and urinary incontinence. Antimuscarinic treatment is frequently discontinued due to side effects or lack of efficacy, whereas injection of onabotulinumtoxin into the detrusor is a minimally invasive procedure with risks of urinary retention, infection and haematuria. Mirabegron, a new β-3 agonist, is a potential new agent for treatment of NDO. Aim of the study was to evaluate the efficacy of mirabegron in SCI patients with NLUTD.. Swiss Paraplegic Center, Nottwil, Switzerland.. A retrospective chart analysis of SCI patient treated with mirabegron.. Fifteen patients with NDO were treated with mirabegron for a period of at least 6 weeks. Significant reduction of the frequency of bladder evacuation per 24 h (8.1 vs 6.4, P=0.003), and of incontinence episodes per 24 h (2.9 vs 1.3, P=0.027) was observed. Furthermore, we observed improvements in bladder capacity (from 365  to 419 ml), compliance (from 28 to 45 ml cm(-1) H(2)0) and detrusor pressure during storage phase (45.8  vs 30 cm H(2)0). At follow-up, 9/15 patients were satisfied with the therapy, 4/15 reported side effects (3 × aggravation of urinary incontinence, 1 × constipation).. Mirabegron may evolve as an alternative in the treatment of NDO. We observed improvements in urodynamic and clinical parameters. Due to the limited number of patients and the retrospective nature of the study, prospective, placebo-controlled studies are necessary.

Topics: Acetanilides; Adult; Female; Follow-Up Studies; Humans; Male; Middle Aged; Retrospective Studies; Severity of Illness Index; Spinal Cord Injuries; Statistics, Nonparametric; Switzerland; Thiazoles; Time Factors; Treatment Outcome; Urinary Bladder, Overactive; Urodynamics; Urological Agents