Dataset Information

Efficacy and Safety of Prucalopride in Chronic Constipation: An Integrated Analysis of Six Randomized, Controlled Clinical Trials.

ABSTRACT:

Background

Prucalopride, a selective, high-affinity 5-hydroxytryptamine 4 receptor agonist, stimulates gastrointestinal and colonic motility and alleviates common symptoms of chronic constipation (CC) in adults. The relative efficacy by gender has not been evaluated.

Aim

To evaluate the global efficacy and safety of prucalopride 2 mg daily in men and women with CC using data from six large, randomized, controlled clinical trials.

Methods

Data were combined from six phase 3 and 4, double-blind, randomized, placebo-controlled, parallel-group trials. The primary efficacy endpoint was the percentage of patients with a mean of ≥3 spontaneous complete bowel movements (SCBMs) per week over 12 weeks of treatment. Safety was assessed throughout all the trials.

Results

Overall, 2484 patients (597 men; 1887 women; prucalopride, 1237; placebo, 1247) were included in the integrated efficacy analysis and 2552 patients were included in the integrated safety analysis. Significantly more patients achieved a mean of ≥3 SCBMs/week over the 12 weeks of treatment in the prucalopride group (27.8 %) than in the placebo group [13.2 %, OR 2.68 (95 % CI 2.16, 3.33), p < 0.001]. Prucalopride had a favorable safety and tolerability profile. Efficacy and safety outcomes were not significantly different between men and women.

Conclusion

The integrated analysis demonstrates the efficacy and safety of prucalopride in the treatment of CC in men and women.

SUBMITTER: Camilleri M

PROVIDER: S-EPMC4943977 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Efficacy and Safety of Prucalopride in Chronic Constipation: An Integrated Analysis of Six Randomized, Controlled Clinical Trials.

Camilleri Michael M Piessevaux Hubert H Yiannakou Yan Y Tack Jan J Kerstens René R Quigley Eamonn M M EMM Ke MeiYun M Da Silva Susana S Levine Amy A

Digestive diseases and sciences 20160407 8

<h4>Background</h4>Prucalopride, a selective, high-affinity 5-hydroxytryptamine 4 receptor agonist, stimulates gastrointestinal and colonic motility and alleviates common symptoms of chronic constipation (CC) in adults. The relative efficacy by gender has not been evaluated.<h4>Aim</h4>To evaluate the global efficacy and safety of prucalopride 2 mg daily in men and women with CC using data from six large, randomized, controlled clinical trials.<h4>Methods</h4>Data were combined from six phase 3 ...[more]

PMID: 27056037

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Project description:BackgroundPrucalopride is a selective, high-affinity, 5-hydroxytryptamine (serotonin) type 4 (5-HT4) receptor agonist with gastrointestinal prokinetic activities. This integrated analysis of data from three double-blind phase III trials (ClinicalTrials.gov: NCT00488137, NCT00483886, NCT00485940) compared the efficacy and safety of prucalopride 2 mg once daily in women with chronic constipation [≤2 spontaneous complete bowel movements (SCBM) per week] in whom laxatives had failed to provide adequate relief with that in the all-patient (AP) population of men and women with chronic constipation who had or had not obtained relief from laxatives.MethodsPatients received prucalopride 2 mg or placebo once-daily for 12 weeks. Efficacy endpoints included an average of ≥3 SCBM/week and average increases of ≥1 SCBM/week and ≥1 SBM/week over this period. A response on any of these three endpoints was considered to be clinically relevant, and an overall response rate was derived for patients satisfying any of these endpoints.ResultsOf the AP population (n = 1318), 936 were women in whom laxatives had failed to provide adequate relief (WLF). More patients on prucalopride 2 mg than placebo had an average of ≥3 SCBM/week (AP 24.4 vs 11.0%; WLF 24.7 vs 9.2%), an average increase of ≥1 SCBM/week (AP 43.5 vs 24.8%; WLF 44.2 vs 22.6%), and an average increase of ≥1 SBM/week (AP 66.7 vs 38.4%; WLF 68.3 vs 37.0%) (all p < 0.001). Significant differences from placebo were evident in week 1 and sustained thereafter. Overall response rates in the AP and WLF populations, respectively, were 69.7 and 71.0% with prucalopride 2 mg and 44.5 and 41.6% with placebo (p < 0.001). Early (weeks 1-4) response predicted ultimate response over time. Common (>10%) adverse events were abdominal pain, nausea, diarrhoea, and headache.ConclusionsPrucalopride 2 mg once daily is effective in WLF. The efficacy and safety profile observed in WLF was similar to that in the total evaluated population of patients with chronic constipation who had or had not obtained adequate relief from laxatives.

Project description:ObjectiveTo evaluate the evidence for the efficacy and safety of acupuncture at Tianshu (ST25) for functional constipation (FC).MethodsWe systematically searched seven databases to identify randomized controlled trials of acupuncture at ST25 alone or in combination with conventional therapy in the treatment of FC. Risk ratios (RRs) and mean differences (MDs) were calculated using RevMan 5.3 with 95% confidence interval (CI).ResultsThe study included ten trials with 1568 participants. Meta-analysis showed that the Cleveland Constipation Score (CCS) for deep needling was significantly lower than that for lactulose (deep needling with low-frequency dilatational wave: MD -0.58, 95% CI -0.94 to -0.22; deep needling with sparse wave: MD -3.67, 95% CI -6.40 to -0.94; deep needling with high-frequency dilatational wave: MD -3.42, 95% CI -5.03 to -1.81). Furthermore, CCS for shallow needling with high-frequency dilatational wave was lower than that for lactulose (MD -1.77, 95% CI -3.40 to -0.14). In addition, when deep needling was combined with high-frequency dilatational wave, the weekly frequency of spontaneous defecation (FSD) was significantly higher than that for lactulose (MD 1.57, 95% CI 0.93 to 2.21). Colonic Transit Time (CTT) scores were significantly higher when deep needling was combined with sparse wave (MD -14.36, 95% CI -18.31 to -10.41) or high-frequency dilatational wave (MD -11.53, 95% CI -19.25 to -3.81). The time of first defecation after treatment (TFD) of the shallow needling therapy was significantly longer than that of the lactulose (MD 13.67, 95% CI 5.66 to 21.67). The CCS 6 months after treatment (CCS6m) for deep needling was significantly lower than that for lactulose (MD -4.90, 95% CI -5.97 to -3.84). Moreover, the FSD 6 months after treatment (FSD6m) for shallow needling was significantly higher than that for lactulose (MD 0.49, 95% CI 0.02 to 0.97). The adverse event (AE) rate for lactulose was significantly higher than that achieved with the needling treatments, and this held true for both deep needling therapy (RR 0.41, 95% CI 0.23 to 0.72) and shallow needling therapy (RR 0.33, 95% CI 0.15 to 0.77).ConclusionsThe meta-analysis demonstrates that acupuncture at ST25 appears to be more effective than lactulose in the treatment of functional constipation. This was found to be especially true for deep needling with high-frequency dilatational wave, which had a greater impact on improving CCS, FSD, CTT, and CCS6m. Additionally, acupuncture at ST25 was shown to be safer than conventional treatment, with the rate of AE being significantly lower for both deep needling and shallow needling. The trial is registered with https://www.crd.york.ac.uk/prospero/(CRD42019141017)).

Project description:BackgroundPrucalopride (1 or 2 mg once daily) is approved for treating adults with chronic idiopathic constipation (CIC).ObjectivesWe determined the effect of age, body mass index (BMI), and renal function on the efficacy and safety of prucalopride in adults with CIC.DesignData were pooled from six 12-week, phase III-IV clinical studies in adults who received prucalopride (1 or 2 mg once daily) or placebo for CIC.MethodsAdults were stratified by age (<50; 50-64; ⩾65 years), BMI (underweight/healthy weight, <25 kg/m2; overweight, 25 to <30 kg/m2; obese, ⩾30 kg/m2), and renal function (normal renal function, estimated glomerular filtration rate (eGFR) ⩾90 mL/min/1.73 m2; mild renal impairment, eGFR 60 to <90 mL/min/1.73 m2; moderate renal impairment, eGFR 30 to <60 mL/min/1.73 m2). The primary efficacy endpoint was the proportion of patients with a mean of ⩾3 complete spontaneous bowel movements/week over 12 weeks. Safety data were evaluated descriptively.ResultsOf 2484 patients stratified by age (prucalopride, n = 1237; placebo, n = 1247), 1402, 708, and 374 were aged <50, 50-64, and ⩾65 years, respectively. Of 2482 patients stratified by BMI (prucalopride, n = 1237; placebo, n = 1245), 1425, 713, and 344 were underweight/healthy weight, overweight, and obese, respectively. Of 2474 patients stratified by renal function (prucalopride, n = 1233; placebo, n = 1241), 1444, 869, and 161 had normal renal function, mild renal impairment, and moderate renal impairment, respectively. More prucalopride-treated than placebo-treated patients achieved the primary efficacy endpoint. The difference was significant for all subgroups, except for the obese and moderate renal impairment subgroups. More prucalopride-treated than placebo-treated patients reported treatment-related adverse events in most subgroups.ConclusionPrucalopride demonstrated efficacy in adults with CIC, irrespective of age, BMI, and renal function. No unexpected safety concerns were identified.Trial registrationClinicalTrials.gov identifiers (https://clinicaltrials.gov/): NCT01147926, NCT01424228, NCT01116206, NCT00483886, NCT00485940, NCT00488137.

Dataset Information

Efficacy and Safety of Prucalopride in Chronic Constipation: An Integrated Analysis of Six Randomized, Controlled Clinical Trials.

Background

Aim

Methods

Results

Conclusion

Publications

Efficacy and Safety of Prucalopride in Chronic Constipation: An Integrated Analysis of Six Randomized, Controlled Clinical Trials.

Similar Datasets

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