OBJECTIVES: To assess the efficacy and safety of umeclidinium bromide versus placebo for people with stable COPD.
SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register (CAGR), ClinicalTrials.gov, the World Health Organization (WHO) trials portal, and the GlaxoSmithKline (GSK) Clinical Study Register, using prespecified terms, as well as the reference lists of all identified studies. Searches are current to April 2017.
SELECTION CRITERIA: We included randomised controlled trials (RCTs) of parallel design comparing umeclidinium bromide versus placebo in people with COPD, for at least 12 weeks.
DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. If we noted significant heterogeneity in the meta-analyses, we subgrouped studies by umeclidinium dose.
MAIN RESULTS: We included four studies of 12 to 52 weeks' duration, involving 3798 participants with COPD. Mean age of participants ranged from 60.1 to 64.6 years; most were males with baseline mean smoking pack-years of 39.2 to 52.3. They had moderate to severe COPD and baseline mean post-bronchodilator forced expiratory volume in one second (FEV1) ranging from 44.5% to 55.1% of predicted normal. As all studies were systematically conducted according to prespecified protocols, we assessed risk of selection, performance, detection, attrition, and reporting biases as low.Compared with those given placebo, participants in the umeclidinium group had a lesser likelihood of developing moderate exacerbations requiring a short course of steroids, antibiotics, or both (odds ratio (OR) 0.61, 95% confidence interval (CI) 0.46 to 0.80; four studies, N = 1922; GRADE: high), but not specifically requiring hospitalisations due to severe exacerbations (OR 0.86, 95% CI 0.25 to 2.92; four studies, N = 1922, GRADE: low). The number needed to treat for an additional beneficial outcome (NNTB) to prevent an acute exacerbation requiring steroids, antibiotics, or both was 18 (95% CI 13 to 37). Quality of life was better in the umeclidinium group (mean difference (MD) -4.79, 95% CI -8.84 to -0.75; three studies, N = 1119), and these participants had a significantly higher chance of achieving a minimal clinically important difference of at least four units in St George's Respiratory Questionnaire (SGRQ) total score compared with those in the placebo group (OR 1.45, 95% CI 1.16 to 1.82; three studies, N = 1397; GRADE: moderate). The NNTB to achieve one person with a clinically meaningful improvement was 11 (95% CI 7 to 29). The likelihood of all-cause mortality, non-fatal serious adverse events (OR 1.33; 95% CI 0.89 to 2.00; four studies, N = 1922, GRADE: moderate), and adverse events (OR 1.06, 95% CI 0.85 to 1.31; four studies, N = 1922; GRADE: moderate) did not differ between umeclidinium and placebo groups. The umeclidinium group demonstrated significantly greater improvement in change from baseline in trough FEV1 compared with the placebo group (MD 0.14, 95% CI 0.12 to 0.17; four studies, N = 1381; GRADE: high). Symptomatic improvement was more likely in the umeclidinium group than in the placebo group, as determined by Transitional Dyspnoea Index (TDI) focal score (MD 0.76, 95% CI 0.43 to 1.09; three studies, N = 1193), and the chance of achieving a minimal clinically important difference of at least one unit improvement was significantly higher with umeclidinium than with placebo (OR 1.71, 95% CI 1.37 to 2.15; three studies, N = 1141; GRADE: high). The NNTB to attain one person with clinically important symptomatic improvement was 8 (95% CI 5 to 14). The likelihood of rescue medication usage (change from baseline in the number of puffs per day) was significantly less for the umeclidinium group than for the placebo group (MD -0.45, 95% CI -0.76 to -0.14; four studies, N = 1531).
AUTHORS' CONCLUSIONS: Umeclidinium reduced acute exacerbations requiring steroids, antibiotics, or both, although no evidence suggests that it decreased the risk of hospital admission due to exacerbations. Moreover, umeclidinium demonstrated significant improvement in quality of life, lung function, and symptoms, along with lesser use of rescue medications. Studies reported no differences in adverse events, non-fatal serious adverse events, or mortality between umeclidinium and placebo groups; however, larger studies would yield a more precise estimate for these outcomes.
Materials and Methods: The whole plant of C. roseus was extracted using methanol extraction method. Phytochemical qualitative screening was carried out for C. roseus extract according to standard procedures used to test for the presence of alkaloid, saponin, terpenoid and steroid. Cytotoxicity was assessed using 3-(4,5-dimethylthiazol-2,5-diphenyltetrazolium bromide (MTT) assay. Plaque reduction assays were carried out to evaluate the antiviral activity of C. roseus extract against herpes simplex virus type 1 (HSV-1). These include post-treatment, pre-treatment and virucidal assays.
Results: C. roseus extract contain secondary metabolites such as alkaloid, saponin and terpenoid but does not contain steroid. Cytotoxicity screening against Vero cells using MTT assay showed that the CC50 values for crude extract of C. roseus was 0.5 mg/mL. The extract prepared from C. roseus possesses phytochemical compound that was non-cytotoxic to the cell with potential antiviral activity. Plaque reduction assays against herpes simplex virus type 1 (HSV-1) showed that the selective indices (SI = CC50 / EC50) of C. roseus extract in post-treatment, pre-treatment and virucidal assays were 36, 20 and 4.7 respectively. The results revealed that the extract prepared from C. roseus possesses phytochemical compound that was non-cytotoxic to the cell with potential antiviral activity.
Conclusion: This study showed that C. roseus extract has promising potential to be explored as anti-HSV-1 agent regardless of the mode of treatment.