MISOPROSTOL DOSAGE IN THE PREVENTION OF NONSTEROIDAL ANTIINFLAMMATORY DRUG-INDUCED GASTRIC AND DUODENAL-ULCERS - A COMPARISON OF 3 REGIMENS
MISOPROSTOL DOSAGE IN THE PREVENTION OF NONSTEROIDAL ANTIINFLAMMATORY DRUG-INDUCED GASTRIC AND DUODENAL-ULCERS - A COMPARISON OF 3 REGIMENS
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DOI：
10.7326/0003-4819-123-5-199509010-00004
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发表时间：
1995-09-01
影响因子：
39.2
通讯作者：
STANTON, DS
中科院分区：
文献类型：
--
作者：
RASKIN, JB;WHITE, RH;STANTON, DS
目的：比较三种米索前列醇给药方案预防与长期非甾体抗炎药 (NSAID) 治疗相关的胃和十二指肠溃疡的有效性和耐受性。设计：一项多中心、12 周、随机、双盲、安慰剂对照、平行、四肢研究。患者：入选标准包括 NSAID 治疗期间出现上消化道症状，且无胃或十二指肠溃疡的内镜证据。共有1623名患者入组；其中 1197 例符合主要入组和治疗方案依从性标准并完成了试验。这 1197 名患者组成了可评估组。 干预措施：患者被随机分配至四种治疗方案中的一种：安慰剂每日四次；安慰剂每日四次；米索前列醇200微克，每日两次，安慰剂每日两次；米索前列醇200μg，每日3次，安慰剂，每日1次；米索前列醇200μg，每日四次。 测量：治疗4、8、12周后进行上消化道内窥镜检查是否有溃疡。通过不良事件监测评估治疗方案的耐受性和安全性。结果：在安慰剂组中，胃溃疡的发生率为15.7%，十二指肠溃疡的发生率为7.5%。每日两次米索前列醇组（8.1%；差异，7.6% [95% CI，2.7% 至 12.5%]；P = 0.002）、每日 3 次（3.9%；差异，11.8% [CI，7.4% 至 16.3%]；P < 0.001）和每日四次（4%；差异，与安慰剂相比，为 11.7% [CI，6.7% 至 16.8%]；P < 0.001）。与每日三次米索前列醇治疗的患者相比，每日两次米索前列醇治疗的患者胃溃疡发生率显着升高（差异为 4.2% [95% CI，0.7% 至 7.7%]；P = 0.02）。米索前列醇在预防胃溃疡方面具有显着的剂量反应效应（P = 0.02）。每日两次米索前列醇组（2.6%；差异，4.9% [CI，1.5% 至 8.2%]；P = 0.004）、每日 3 次（3.3%；差异，4.2% [CI，0.6% 至 7.7%]；P = 0.019）和每日四次（1.4%；差异，与安慰剂相比，为 6.1% [CI，2.6% 至 9.6%]；P = 0.007）。每天两次接受米索前列醇的患者与每天三次接受米索前列醇的患者之间没有发现显着差异，并且十二指肠溃疡没有剂量反应效应。每日两次米索前列醇治疗组（12%）和每日三次米索前列醇治疗组（12%）因不良事件退出的发生率显着低于每日四次米索前列醇治疗组（20%）。每日四次米索前列醇治疗组（74%）的胃肠道不良事件发生率显着高于安慰剂组（62%）。结论：米索前列醇，每天两次或三次，每次 200 μg，对长期接受 NSAID 治疗的患者具有显着的预防胃和十二指肠溃疡的作用。这些剂量比目前批准的每天四次 200 微克的治疗方案具有更好的耐受性。
Objective: To compare the effectiveness and tolerability of three misoprostol dosing regimens for the prevention of gastric and duodenal ulcers associated with long-term nonsteroidal anti-inflammatory drug (NSAID) therapy.Design: A multicenter, 12-week, randomized, double-blind, placebo-controlled, parallel, four-limb study.Patients: Eligibility criteria included upper gastrointestinal symptoms during NSAID therapy and no endoscopic evidence of gastric or duodenal ulcers. A total of 1623 patients was enrolled; 1197 of these met major accession and regimen-compliance criteria and completed the trial. These 1197 patients composed the evaluable group.Interventions: Patients were randomly assigned to one of four regimens: placebo four times daily; 200 mu g of misoprostol twice daily and placebo twice daily; 200 mu g of misoprostol three times daily and placebo once daily; and 200 mu g of misoprostol four times daily.Measurements: Upper gastrointestinal endoscopic examinations for ulcers were done after 4, 8, and 12 weeks of therapy. Tolerability and safety of the regimens were assessed by adverse-event monitoring.Results: In the placebo group, the incidence of gastric ulcers was 15.7% and the incidence of duodenal ulcers was 7.5%. The incidence of gastric ulcers was significantly lower in the groups receiving misoprostol twice daily (8.1%; difference, 7.6% [95% CI, 2.7% to 12.5%]; P = 0.002), three times daily (3.9%; difference, 11.8% [CI, 7.4% to 16.3%]; P < 0.001), and four times daily (4%; difference, 11.7% [CI, 6.7% to 16.8%]; P < 0.001) compared with placebo. The gastric ulcer rate was significantly higher in patients receiving misoprostol twice daily compared with those receiving misoprostol three times daily (difference, 4.2% [95% CI, 0.7% to 7.7%]; P = 0.02). A significant (P = 0.02) misoprostol dose-response effect was noted in the prevention of gastric ulcers. The incidence of duodenal ulcers was significantly lower in the groups receiving misoprostol twice daily (2.6%; difference, 4.9% [CI, 1.5% to 8.2%]; P = 0.004), three times daily (3.3%; difference, 4.2% [CI, 0.6% to 7.7%]; P = 0.019), and four times daily (1.4%; difference, 6.1% [CI, 2.6% to 9.6%]; P = 0.007) compared with placebo. No significant difference was detected between patients receiving misoprostol twice daily and those receiving misoprostol three times daily, and no dose-response effect was noted with duodenal ulcers. The incidence of withdrawals for adverse events was significantly lower in the groups receiving misoprostol twice daily (12%) and three times daily (12%) than in the group receiving it four times daily (20%). The incidence of gastrointestinal adverse events was significantly higher in the group receiving misoprostol four times daily (74%) than in the placebo group (62%).Conclusion: Misoprostol, 200 mu g twice or three times daily, offers substantial protection against gastric and duodenal ulcers in patients receiving long-term NSAID therapy. These dosages were better tolerated than the currently approved regimen of 200 mu g four times daily.