Lansoprazole for secondary prevention of gastric or duodenal ulcers associated with long-term non-steroidal anti-inflammatory drug (NSAID) therapy: results of a prospective, multicenter, double-blind, randomized, double-dummy, active-controlled trial

Kentaro Sugano, Teiji Kontani, Shinichi Katsuo, Yoshinori Takei, Nobuhiro Sakaki, Kiyoshi Ashida, Yuji Mizokami, Masahiro Asaka, Shigeyuki Matsui, Tatsuya Kanto, Satoshi Soen, Tsutomu Takeuchi, Hideyuki Hiraishi, Naoki Hiramatsu, Kentaro Sugano, Teiji Kontani, Shinichi Katsuo, Yoshinori Takei, Nobuhiro Sakaki, Kiyoshi Ashida, Yuji Mizokami, Masahiro Asaka, Shigeyuki Matsui, Tatsuya Kanto, Satoshi Soen, Tsutomu Takeuchi, Hideyuki Hiraishi, Naoki Hiramatsu

Abstract

Background: Low-dose lansoprazole has not been intensively evaluated for its efficacy in the prevention of recurrent gastric or duodenal ulcers in patients receiving long-term non-steroidal anti-inflammatory drug (NSAID) therapy for pain relief in such diseases as rheumatoid arthritis, osteoarthritis, and low back pain.

Methods: This multi-center, prospective, double-blind, randomized, active-controlled study involving 99 sites in Japan was designed to compare the efficacy of lansoprazole (15 mg daily) with gefarnate (50 mg twice daily). Patients with a history of gastric or duodenal ulcers who required long-term NSAID therapy were randomized to receive lansoprazole 15 mg daily (n = 185) or gefarnate 50 mg twice daily (n = 181) and followed up for 12 months or longer prospectively.

Results: The cumulative incidence of gastric or duodenal ulcer at days 91, 181, and 361 from the start of the study was calculated by the Kaplan-Meier method as 3.3, 5.9, and 12.7%, respectively, in the lansoprazole group versus 18.7, 28.5, and 36.9%, respectively, in the gefarnate group. The risk for ulcer development was significantly (log-rank test, P < 0.0001) lower in the lansoprazole group than in the gefarnate group, with the hazard ratio being 0.2510 (95% CI 0.1400-0.4499). A long-term follow-up study showed an acceptable safety profile for low-dose lansoprazole therapy, with diarrhea as the most frequent adverse event.

Conclusion: Lansoprazole was superior to gefarnate in reducing the risk of gastric or duodenal ulcer recurrence in patients with a definite history of gastric or duodenal ulcers who required long-term NSAID therapy.

Figures

Fig. 1
Fig. 1
Patient disposition in this trial (2010 CONSORT flow diagram). As noted in the manuscript, the study was prematurely terminated for ethical reasons before accrual of the expected number of patients. GI gastrointestinal
Fig. 2
Fig. 2
Kaplan–Meier estimates of the cumulative incidence of gastric or duodenal ulcers in the treatment groups

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