ObjectiveTo evaluate the potential of solifenacin 5 mg combined with mirabegron 25 or 50 mg to deliver superior efficacy compared with monotherapy, with acceptable tolerability, in the general overactive bladder (OAB) population with urinary incontinence (UI). Patients and MethodsAfter a 4-week placebo run-in, patients aged ≥18 years with wet OAB (urgency, urinary frequency and UI) for ≥3 months who recorded on average ≥8 micturitions/24 h, ≥1 urgency episode/24 h, and ≥3 UI episodes over the 7-day micturition diary, were eligible for randomisation to double-blind treatment [2:2:1:1:1:1 ratio, solifenacin 5 mg + mirabegron 25 mg (combined S5 + M25 group); solifenacin 5 mg + mirabegron 50 mg (combined S5 + M50 group); solifenacin 5 mg; mirabegron 25 mg; mirabegron 50 mg; or placebo for 12 weeks], and 2-weeks' single-blind, placebo run-out. Co-primary efficacy variables were change from baseline to end of treatment (EoT) in the mean number of UI episodes/24 h and micturitions/24 h, assessed using a 7-day electronic micturition diary. Secondary efficacy variables included change from baseline to EoT in the mean volume voided/micturition, change from baseline at weeks 4, 8, 12 and EoT in mean number of UI episodes/ 24 h, micturitions/24 h, urgency episodes/24 h, urgency UI (UUI) episodes/24 h and nocturia episodes/24 h; the percentage of patients (responders) achieving zero UI episodes/24 h at EoT in the last 7 days prior to each visit, micturition frequency normalisation (<8 episodes/24 h) at weeks 4, 8, 12 and EoT; and the number of UUI episodes and nocturia episodes in the 7-day diary. Safety assessments included incidence and frequency of treatment-emergent adverse events (TEAEs), post-void residual (PVR) urine volume, and changes from baseline in laboratory parameters. ResultsWhilst the combined S5 + M50 group was superior to solifenacin 5 mg for UI, with a mean (standard error) adjusted difference of À0.20 (0.12) UI episodes/24 h (95% confidence interval À0.44, 0.04, P = 0.033), there was no statistical superiority vs mirabegron 50 mg [À0.23 (0.12) UI episodes/24 h; P = 0.052]. In secondary analyses, all active treatment groups had greater improvements in UI episodes/ 24 h vs placebo, with effect sizes for the combined therapy groups (combined S5 + M25 group: À0.70 episodes/24 h; combined S5 + M50 group: À0.65 episodes/24 h) that were substantially higher than those obtained with monotherapy (range À0.37 episodes/24 h for mirabegron 25 mg to À0.45 episodes/24 h for solifenacin 5 mg). For micturitions/24 h, adjusted change from baseline to EoT was greater in the combined therapy groups vs monotherapies (combined S5 + M50 group, nominal P values 0.006 and <0.001 vs solifenacin 5 mg and mirabegron 50 mg, respectively; combined S5 + M25 group, nominal P values 0.040 and 0.001 vs solifenacin 5 mg and mirabegron 25 mg, respectively). All active treatment groups had greater improvements in the mean numbers of micturitions/24 h vs placebo, with effect sizes for the combined therapy groups (combined S5 + M25 group: À0....
This study looked at the safety and efficacy of a combination of solifenacin succinate 5mg plus mirabegron 50mg tablets over 12 mo in patients with the overactive bladder (OAB) symptoms of increased urination frequency, heightened urgency to urinate, and unintentional passing of urine. We compared this treatment with solifenacin succinate 5mg or mirabegron 50mg alone, and found that the combination treatment was well tolerated by patients and led to greater improvements in symptoms. This novel combination could be an improved treatment option in the clinical setting for patients with OAB. This study is registered at ClinicalTrials.gov as NCT02045862.
Background Fidaxomicin, a narrow-spectrum antibiotic approved for Clostridioides (Clostridium) difficile infection (CDI) in adults, is associated with lower rates of recurrence than vancomycin; however, pediatric data are limited. This multicenter, investigator-blind, phase 3, parallel-group trial assessed the safety and efficacy of fidaxomicin in children. Methods Patients aged <18 years with confirmed CDI were randomized 2:1 to 10 days of treatment with fidaxomicin (suspension or tablets, twice daily) or vancomycin (suspension or tablets, 4 times daily). Safety assessments included treatment-emergent adverse events. The primary efficacy end point was confirmed clinical response (CCR), 2 days after the end of treatment (EOT). Secondary end points included global cure (GC; CCR without CDI recurrence) 30 days after EOT (end of study; EOS). Plasma and stool concentrations of fidaxomicin and its active metabolite OP-1118 were measured. Results Of 148 patients randomized, 142 were treated (30 <2 years old). The proportion of participants with treatment-emergent adverse events was similar with fidaxomicin (73.5%) and vancomycin (75.0%). Of 3 deaths in the fidaxomicin arm during the study, none were CDI or treatment related. The rate of CCR at 2 days after EOT was 77.6% (76 of 98 patients) with fidaxomicin and 70.5% (31 of 44) with vancomycin, whereas the rate of GC at EOS was significantly higher in participants receiving fidaxomicin (68.4% vs 50.0%; adjusted treatment difference, 18.8%; 95% confidence interval, 1.5%–35.3%). Systemic absorption of fidaxomicin and OP-1118 was minimal, and stool concentrations were high. Conclusions Compared with vancomycin, fidaxomicin was well tolerated and demonstrated significantly higher rates of GC in children and adolescents with CDI. ClinicalTrials.gov identifier NCT02218372
With frequencies varying up to 20%, treatment resistant pulmonary failure is a major life-threatening complication in COVID-19 (SARS-CoV-2, HCoV19) disease pathology. Both acute respiratory distress syndrome (ARDS), proposed to be caused by an over-reacting immune system which floods the lung with edema, a liquid consisting of inflammatory cells, and diminished lung perfusion, have been postulated to cause this treatment resistant lung failure. Aging, co-morbidities, male gender and obesity are pre-existing factors associated with the more severe outcome. Thrombosis is more frequently observed than usually seen during ICU admission. Different hypotheses explaining the pathophysiological cascade leading to fast progressing severe COVID-19 disease and how to counteract it have been proposed. A variety of intervention studies to control severity are ongoing or planned. Not suggested so far, we here hypothesize that the inflammatory lipid modulator prostaglandin E2 (PGE2) executes a prominent role in COVID-19 pathophysiology. Based on this we suggest measuring PGE2 in patients and evaluating selective inhibition of the human microsomal prostaglandin E synthase-1 (mPGES-1) as a potential innovative therapeutic approach in this devastating condition for which sonlicromanol, a drug currently in phase 2b studies for mitochondrial disease, is a candidate.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.