Digestive Diseases and Sciences

, Volume 31, Supplement 2, pp 75S–80S

A multicenter international controlled comparison of two dosage regimens of misoprostol with cimetidine in treatment of gastric ulcer in outpatients

  • D. Rachmilewitz
  • J. W. Chapman
  • P. A. Nicholson
  • International Study Group
Prostaglandins in Peptic Ulcer Disease Clinical Efficacy of Misoprostol


In this double-blind, parallel-group multicenter study, patients with endoscopically proven gastric ulcers were randomly allocated to treatment with either 50 μg or 200 μg of misoprostol or 300 mg of cimetidine, each given four times daily for four weeks. Endoscopic, clinical and laboratory assessments were made before treatment and after four weeks; clinical and laboratory assessments were repeated at two weeks. In the Korean center, assessments were also made after six weeks and at eight weeks of treatment. Six hundred and thirty patients were studied. The three treatment groups were similar in age and occupation. However, the proportion of men in the misoprostol 50-μg, 200-μg and cimetidine 300-mg groups was 67%, 63%, and 59%, respectively. Therapeutic success was defined as complete healing of all ulcers, judged endoscopically. On an intent-to-treat basis, which includes all losses to follow-up and withdrawals as treatment failures, ulcer healing rates in the misoprostol 50-μg, 200-μg and cimetidine 300-mg groups were 39%, 51%, and 58%, respectively. In the Korean center, the healing rates were 38%, 64%, and 70%, respectively, after eight weeks of treatment. There was no statistically significant difference in the healing rates at four weeks between the misoprostol 200-μg and cimetidine 300-mg groups (P=0.16). The healing rate with the misoprostol 200-μg dose was significantly better than with the 50-μg dose (P=0.008). Cimetidine 300 mg relieved global pain significantly better than misoprostol 200 μg at two weeks (P=0.047) but not at four weeks. The 200-μg dose of misoprostol relieved pain significantly better than the 50-μg dose at four weeks (P=0.019), but not at two weeks. All three treatments were well tolerated. Severe adverse events were rare.


  1. 1.
    Wilson DE, Quadros E, Rajapaksa T, Adams A, Noar M: Effects of misoprostol on gastric acid and mucus secretion in man. Dig Dis Sci 31(Suppl):126S-129S, 1986Google Scholar
  2. 2.
    Isenberg JI, Hogan DL, Selling JA, Koss MA: Duodenal bicarbonate secretion in humans: role of prostaglandins. Dig Dis Sci 31(Suppl):130S, 1986 (abstract)Google Scholar
  3. 3.
    Leung FW, Miller JC, Guth PH: Dissociated effects of misoprostol on gastric acid secretion and mucosal blood flow. Dig Dis Sci 31(Suppl):86S-90S, 1986Google Scholar
  4. 4.
    McGuigan JE, Chang Y, Dajani EZ: Effect of misoprostol, an antiulcer prostaglandin, on serum gastrin in patients with duodenal ulcer. Dig Dis Sci 31(Suppl):120S-125S, 1986Google Scholar
  5. 5.
    Fimmel CJ, Blum AL: Acid inhibition but no protection from bile salt damage by a prostaglandin E1 analogue in man. Gastroenterology 84[5(2)]:1151, 1983 (abstract)Google Scholar
  6. 6.
    Agrawal NM, Godiwala T, Arimura A, Dajani EZ: Compartive cytoprotective effects against alcohol insult. Misoprostol versus cimetidine. Dig Dis Sci 31(Suppl):142S, 1986 (abstract)Google Scholar
  7. 7.
    Cohen MM, Clark L, Armstrong L, D'Souza J: Reduced aspirin-induced fecal blood loss with simultaneous administration of misoprostol (PGE1 methyl analogue). Gastroenterology 84[5(2)]:1126, 1983 (abstract)Google Scholar
  8. 8.
    Hunt JN, Smith JL, Jiang CL, Kessler L: Effect of synthetic prostaglandin E1 analog on aspirin-induced gastric bleeding and secretion. Dig Dis Sci 28(10):897–902, 1984Google Scholar
  9. 9.
    Silverstein FE, Kimmey MB, Saunders DR, Levine DS: Gastric protection by misoprostol against 1300 mg of aspirin: An endoscopic study. Dig Dis Sci 31(Suppl):137S-141S, 1986Google Scholar
  10. 10.
    Lanza FL: A double-blind study of prophylactic effect of misoprostol on lesions of gastric and duodenal mucosa induced by oral administration of tolmetin in healthy subjects. Dig Dis Sci 31(Suppl):131S-136S, 1986Google Scholar
  11. 11.
    Nicholson PA: A multicenter international controlled comparison of two dosage regimens of misoprostol and cimetidine in the treatment of duodenal ulcer in outpatients. Dig Dis Sci 30(Suppl):171S-177S, 1985Google Scholar
  12. 12.
    Rohner HG, Weinbeck M, Feyerabend H, Backwinkel KP, Pelz W, Pistauer H, Bock H, Mares A, Weiss W, Beckenbach HP: Two or four daily doses of cimetidine in the treatment of gastric ulcer. Z Gastroenterol 22:382–387, 1984Google Scholar
  13. 13.
    Bright-Asare P, Sontag SJ, Gould RJ, Brand DL, Roufail WM: Efficacy of misoprostol (twice daily dosage) in acute healing of duodenal ulcer: A multicenter, double-blind, controlled trial. Dig Dis Sci 31(Suppl):63S-67S, 1986Google Scholar
  14. 14.
    Misiewicz JJ: Peptic ulceration and its correlation with symptoms. Clin Gastroenterol 7:571–582, 1978Google Scholar
  15. 15.
    Frost F, Ratibek I, Rune SJ, Birger-Jensen K, Godmand-Hoyer E, Krag E, Rask-Madsen J, Wulff HR, Garbol J, Gotlieb-Jensen K, Hojlung M, Nissen VR: Cimetidine in patients with gastric ulcer: A multicenter controlled trial. Br Med J 2:795–797, 1977Google Scholar
  16. 16.
    Lam SK, Lau WY, Choi TK, Lai CL, Lok ASF, Hui WM, Ng MMT, Choi SKY: Prostaglandin E1 (misoprostol) overcomes the adverse effect of chronic cigarette smoking on duodenal-ulcer healing. Dig Dis Sci 31(Suppl):68S-74S, 1986Google Scholar

Copyright information

© Plenum Publishing Corporation 1986

Authors and Affiliations

  • D. Rachmilewitz
    • 2
    • 1
  • J. W. Chapman
    • 2
    • 1
  • P. A. Nicholson
    • 2
    • 1
  • International Study Group
    • 2
    • 1
  1. 1.G.DD. Searle & CompanyHigh WycombeEngland
  2. 2.Department of GastroenterologyHadassah University HospitalJerusalemIsrael

Personalised recommendations