Ehsanullah and colleagues assessed the prophylactic effect of ranitidine 150 mg twice daily in patients who needed one of the non-steroidal anti-inflammatory drugs (NSAIDs), including naproxen, piroxicam, diclofenac, and indomethacin. The investigators also assessed the risk factors to help target such treatment to specific groups of patients.

This double-blind, placebo controlled, randomized, parallel group, multicenter study, conducted at secondary referral centres in five European countries included endoscopic assessments at week 0, 4, and 8.

A total of 297 patients with rheumatoid arthritis or osteoarthritis, aged above 18 years, without any lesions in the stomach and duodenum at baseline endoscopy (after one week without taking NSAIDs) were included in the study.

Patients who were being treated with other antirheumatic drugs, concomitant ulcerogenic agents, or received treatment for peptic ulcers within the previous 30 days were excluded. Overall, 263 patients completed the trial.

Patients were randomized to receive either ranitidine 150 mg twice a day or placebo (plus selected NSAID) within five days of the baseline endoscopy for two consecutive periods of four weeks. Patients were allowed to take paracetamol during the study, but not antacids. Patients were withdrawn if the most severe grade of damage was identified at the four week endoscopy or when indicated, or with lesser damage, at the discretion of the investigator. The study end point was frequency of gastric and duodenal ulceration or lesions, or both.

Findings of the study -

• The cumulative incidence of peptic ulceration by 8 weeks was 10.3% (27/263) - 1.5% developed duodenal ulceration in the ranitidine group, compared with 8% in the placebo group.
• The frequency of gastric ulceration was the same, i.e., 6% for the two groups at 8 weeks.
• Significantly fewer gastric lesions were noted in the ranitidine group by 8 weeks.
• The frequency of non-ulcerative lesions in the duodenum was not different for the two groups at either time point.
• In all, 16% patients taking piroxicam developed peptic ulceration; of these two-thirds had duodenal ulceration.
• Patients having a history of peptic ulcer were vulnerable to recurrent ulceration; however, ranitidine provided some protection against it.

The study concluded that ranitidine treatment could lead to significant reduction in the incidence of duodenal ulceration when prescribed along with one of four commonly used NSAIDs.

Source: Ehsanullah RS, Page MC, Tildesley G, Wood JR. Prevention of gastroduodenal damage induced by non-steroidal anti-inflammatory drugs: controlled trial of ranitidine. British Medical Journal 1988;297:1017.