Jamal M Mazen, Adams Atoya B, Jansen Jan-Peter, Webster Lynn R
1] Department of Internal Medicine, Long Beach VA Medical Center, Long Beach, California, USA [2] Department of Medicine, UCI College of Medicine, Irvine, California, USA.
AB Clinical Trials, Las Vegas, Nevada, USA.
Am J Gastroenterol. 2015 May;110(5):725-32. doi: 10.1038/ajg.2015.106. Epub 2015 Apr 28.
This multicenter, phase 3 trial evaluated oral lubiprostone for constipation associated with non-methadone opioids in patients with chronic noncancer-related pain.
Adults with opioid-induced constipation (OIC; <3 spontaneous bowel movements [SBMs] per week) were randomized 1:1 to double-blind lubiprostone 24 μg or placebo twice daily for 12 weeks. The primary end point was the overall SBM response rate. Responders had at least moderate response (≥1 SBM improvement over baseline frequency) in all treatment weeks with available observed data, as well as full response (≥3 SBMs per week) for at least 9 of the 12 treatment weeks.
In total, 431 patients were randomized; 212 each received lubiprostone and placebo, and 7 were not treated. Overall, the SBM response rate was significantly higher for patients treated with lubiprostone vs. placebo (27.1 vs. 18.9%, respectively; P=0.030). Overall mean change from baseline in SBM frequency was significantly greater with lubiprostone vs. placebo (3.2 vs. 2.4, respectively; P=0.001). The median time to first SBM was significantly shorter with lubiprostone vs. placebo (23.5 vs. 37.7 h, respectively; P=0.004). Compared with placebo, the patients treated with lubiprostone exhibited significant improvements in straining (P=0.004), stool consistency (P<0.001), and constipation severity (P=0.010). No significant differences were observed in quality-of-life measures or the use of rescue medication; however, the percentage of patients who used rescue medication was consistently lower in the lubiprostone group than in the placebo group at months 1 (34.9 vs. 37.7%), 2 (23.4 vs. 26.6%), and 3 (20.5 vs. 22.0%). Adverse events (AEs) >5% were diarrhea, nausea, vomiting, and abdominal pain (lubiprostone: 11.3, 9.9, 4.2, and 7.1%, respectively; placebo, 3.8, 4.7, 5.2, and 0%, respectively). None of the serious AEs (lubiprostone, 3.3%; placebo, 2.8%) were related to lubiprostone.
Lubiprostone significantly improved symptoms of OIC and was well tolerated in patients with chronic noncancer pain.
本多中心3期试验评估了口服鲁比前列酮用于治疗慢性非癌性疼痛患者中与非美沙酮类阿片药物相关的便秘。
患有阿片类药物引起的便秘（OIC；每周自发排便次数<3次）的成年人按1:1随机分为两组，双盲接受每日两次24μg鲁比前列酮或安慰剂治疗，为期12周。主要终点是总体自发排便反应率。在所有有可观察数据的治疗周中，反应者至少有中度反应（比基线频率改善≥1次自发排便），并且在12个治疗周中的至少9周有完全反应（每周≥3次自发排便）。
总共431名患者被随机分组；每组212名分别接受鲁比前列酮和安慰剂治疗，7名未接受治疗。总体而言，接受鲁比前列酮治疗的患者的自发排便反应率显著高于接受安慰剂治疗的患者（分别为27.1%和18.9%；P=0.030）。与安慰剂相比，鲁比前列酮治疗组自发排便频率从基线的总体平均变化显著更大（分别为3.2和2.4；P=0.001）。首次自发排便的中位时间，鲁比前列酮组显著短于安慰剂组（分别为23.5小时和37.7小时；P=0.004）。与安慰剂相比，接受鲁比前列酮治疗的患者在用力排便（P=0.004）、大便稠度（P<0.001）和便秘严重程度（P=0.010）方面有显著改善。在生活质量指标或急救药物使用方面未观察到显著差异；然而，在第1个月（34.9%对37.7%）、第2个月（23.4%对26.6%）和第3个月（20.5%对22.0%），鲁比前列酮组使用急救药物的患者百分比始终低于安慰剂组。发生率>5%的不良事件为腹泻、恶心、呕吐和腹痛（鲁比前列酮组分别为11.3%、9.9%、4.2%和7.1%；安慰剂组分别为：3.8%、4.7%、5.2%和0%）。严重不良事件（鲁比前列酮组为3.3%；安慰剂组为2.8%）均与鲁比前列酮无关。
鲁比前列酮显著改善了阿片类药物引起的便秘症状，并且在慢性非癌性疼痛患者中耐受性良好。
