The Journal of Informed Pharmacotherapy 2000;2:209-211.
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Reviewers_Name: Peter J. Zed, B.Sc., B.Sc. (Pharm), Pharm.D.
Reviewers_Specialty: Pharmacy/Emergency Medicine
Agrawal NM, Campbell DR, Safdi MA, Lukasik NL, Huang B, Haber MM for the NSAID-Associated Gastric Ulcer Study Group. Superiority of lansoprazole vs. ranitidine in healing non-steroidal anti-inflammatory drug-induced gastric ulcers. Arch Intern Med 2000;160:1455-61. PubMed Citation
This study was a prospective, multicentre, double-blind, parallel group study
designed to identify the optimal antisecretory therapy for healing of gastric
ulcers in patients using an nonsteroidal anti-inflammatory drug (NSAID) and the
impact of Helicobacter pylori infection on gastric ulcer healing.
Patients aged 18 years or older with an active non-malignant gastric ulcer (primary lesions >5 mm in diameter) documented by endoscopic and biopsy findings and who were receiving a stable dose of an NSAID for at least the previous month were eligible for enrollment into the study. The primary study endpoint was gastric ulcer healing rate at 8 weeks. Secondary endpoints included gastric ulcer healing rate at 8 weeks in H. pylori-infected and non-infected patients. Patient symptoms were also assessed using a patient diary that was completed on a daily basis.
1. Was assignment of patients randomized?
Yes. All patients were assigned randomly in a 1:1:1 ratio to receive ranitidine 150 mg orally twice daily, or lansoprazole 15 or 30 mg orally once daily for 8 weeks.
Yes. All three groups demonstrated similar baseline parameters at the start of the trial.
Yes. Patients also received antacid tablets (400 mg each of aluminum hydroxide and magnesium hydroxide and 25 mg of simethicone) and were instructed only to use them for symptom relief as needed. Patients were also instructed to avoid any other antiulcer (e.g. H2-receptor antagonist,> misoprostol, or sucralfate) or ulcerogenic medications (except an NSAID or low dose aspirin) other than the study medications until completion of the study.
1. How large was the treatment effect?
The primary endpoint, gastric ulcer healing at 8 weeks, occurred in 53% patients treated with ranitidine compared to 69% of patients who received lansoprazole 15 mg (p=0.01 vs. ranitidine, 95% confidence interval [CI] for the difference between groups 3.2-28.0) and 73% of patients who received lansoprazole 30 mg, (p=0.009 vs. ranitidine, 95% CI 7.4-31.8). This correlates to an absolute risk reduction (ARR) of 16-20% and a number needed to treat of 5 and 7 for lansoprazole 15 and 30 mg daily, respectively, as compared to ranitidine for ulcer healing at 8 weeks.
The secondary endpoint of gastric ulcer healing rate at 8 weeks in H. pylori-infected and non-infected patients was not different between the groups. As with the total population, the lansoprazole 15 mg and 30 mg recipients had higher gastric ulcer healing rates at 8 weeks in both the H. pylori-infected (67% and 82%, respectively) and non-infected patients (70% and 69%, respectively) as compared to ranitidine (60% and 51% for H. pylori positive and negative patients, respectively).
During the 8 treatment weeks, there was no difference in the improvement in symptom relief, however a statistically significant reduction in antacid use was observed with lansoprazole 15 mg (p<0.01) and 30 mg (p<0.05) use as compared to ranitidine. In particular, there were fewer antacid tablets per day (ranitidine 1.11 vs. lansoprazole 15 mg 0.86 (p<0.05) vs. lansoprazole 30 mg 0.78 (p<0.01)) and a smaller percentage of days of antacid use (ranitidine 35.6% vs. lansoprazole 15 mg 30.9% (p=ns) vs. lansoprazole 30 mg 28.7% (p<0.05)). The authors did not provide information regarding any actual OTC use of H2-receptor antagonists or other medications.
Overall, treatment-related adverse effects occurred in 11% of ranitidine-treated patients and 8% and 9% of lansoprazole 15 mg and 30 mg recipients, respectively. The most common adverse effect reported by the patients was diarrhea. There were no statistically significant differences among treatment groups for any specific drug-related adverse effect.
2. How precise was the estimate of the treatment effect?
The 95% CI for the primary endpoint of gastric ulcer healing at 8 weeks did not include zero, thus indicating statistical significance. In this author's opinion, the lower end of the CI range still represents a clinically significant difference between treatment groups.
2. Were all clinically important outcomes considered?
Yes, although health-related quality of life and pharmacoeconomic analyses would have been useful.
1. Yeomans ND, Tulassay Z, Juhasz L, et al, A comparison of omeprazole with ranitidine for ulcers associated with nonsteroidal anti-inflammatory drugs. N Engl J Med 1998;338:719-26
2. Hawkey CJ, Karrasch JA, Szczepanski L, et al. Omeprazole compared
with misoprostol for ulcers associated with nonsteroidal anti-inflammatory drugs. N Engl J Med 1998;338:727-34.
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