Ehsanullah R S, Page M C, Tildesley G, Wood J R
Department of Gastroenterology, Glaxo Group Research Limited, Greenford, Middlesex.
BMJ. 1988 Oct 22;297(6655):1017-21. doi: 10.1136/bmj.297.6655.1017.
To evaluate the prophylactic effect of ranitidine 150 mg twice daily in patients requiring one of the following non-steroidal anti-inflammatory drugs: naproxen, piroxicam, diclofenac, and indomethacin. In addition, risk factors were studied in order to help in targeting of such treatment to specific groups of patients.
Double blind, placebo controlled, randomised, parallel group with endoscopic assessments at 0, 4, and 8 weeks.
Multicentre outpatient study at secondary referral centres in five European countries. PATIENTS--297 patients with rheumatoid arthritis or osteoarthritis over the age of 18 without lesions in the stomach and duodenum at baseline endoscopy (after one week without taking non-steroidal anti-inflammatory drugs). Those taking other antirheumatic agents, concomitant ulcerogenic drugs, or treatment for peptic ulcers within the previous 30 days were excluded. Age, sex, arthritic disease, and type of non-steroidal anti-inflammatory drug used were comparable in the two treatment groups. In all, 263 patients completed the trial.
Ranitidine 150 mg twice daily or placebo (plus the selected non-steroidal anti-inflammatory drug) was prescribed within five days after the baseline endoscopy for two consecutive periods of four weeks. Paracetamol was permitted during the study, but not antacids. Patients were withdrawn if the most severe grade of damage (including ulceration) was found at the four week endoscopy or when indicated, or with lesser damage at the investigator's discretion.
Frequency of gastric and duodenal ulceration or lesions, or both.
The cumulative incidence of peptic ulceration by eight weeks was 10.3% (27/263); 2 out of 135 (1.5%) developed duodenal ulceration in the ranitidine group, compared with 10 out of 126 (8%) taking placebo. The frequency of gastric ulceration was the same (6%) for the two groups at eight weeks. Though significantly fewer gastric lesions developed in the ranitidine group by eight weeks. The frequency of non-ulcerative lesions in the duodenum did not differ greatly for the two groups at either time point. Twelve out of 75 (16%) patients taking piroxicam developed peptic ulceration, of whom two thirds had duodenal ulceration. Patients with a history of peptic ulcer were particularly susceptible to recurrent ulceration, against which ranitidine offered some protection.
Ranitidine 150 mg twice daily significantly reduced the incidence of duodenal ulceration but not gastric ulceration when prescribed concomitantly with one of four commonly used non-steroidal anti-inflammatory drugs.
评估雷尼替丁每日两次、每次150毫克对需要使用以下非甾体抗炎药之一的患者的预防效果：萘普生、吡罗昔康、双氯芬酸和吲哚美辛。此外，还研究了风险因素，以帮助针对特定患者群体进行此类治疗。
双盲、安慰剂对照、随机、平行组研究，在0、4和8周进行内镜评估。
欧洲五个国家二级转诊中心的多中心门诊研究。患者——297例年龄超过18岁的类风湿性关节炎或骨关节炎患者，基线内镜检查（在停用非甾体抗炎药一周后）时胃和十二指肠无病变。排除在过去30天内服用其他抗风湿药、同时服用致溃疡药物或接受消化性溃疡治疗的患者。两个治疗组在年龄、性别、关节炎疾病和使用的非甾体抗炎药类型方面具有可比性。共有263例患者完成了试验。
在基线内镜检查后5天内，连续两个为期四周的时间段，每日两次、每次150毫克服用雷尼替丁或安慰剂（加所选非甾体抗炎药）。研究期间允许使用对乙酰氨基酚，但不允许使用抗酸剂。如果在四周内镜检查时发现最严重的损伤等级（包括溃疡），或在必要时，或根据研究者的判断有较轻损伤，则将患者撤出。
胃和十二指肠溃疡或病变（或两者兼有）的发生率。
到八周时消化性溃疡的累积发生率为10.3%（27/263）；雷尼替丁组135例中有2例（1.5%）发生十二指肠溃疡，而服用安慰剂组126例中有10例（8%）发生。两组在八周时胃溃疡的发生率相同（6%）。尽管到八周时雷尼替丁组发生的胃部病变明显较少。两个组在两个时间点十二指肠非溃疡性病变的发生率差异不大。服用吡罗昔康的75例患者中有12例（16%）发生消化性溃疡，其中三分之二为十二指肠溃疡。有消化性溃疡病史的患者特别容易复发溃疡，雷尼替丁对此有一定的保护作用。
每日两次、每次150毫克服用雷尼替丁与四种常用非甾体抗炎药之一合用时，可显著降低十二指肠溃疡的发生率，但不能降低胃溃疡的发生率。
