Combination of enprostil and cimetidine is more effective than cimetidine alone in treating gastric ulcer: prospective multicenter randomized controlled trial.
OBJECTIVE
Little is known about the clinical efficacy of co-therapy of enprostil, a prostaglandin E2 analogue, with a histamine H2-receptor antagonist. We aimed to assess the additive benefit of enprostil in combination with cimetidine for treating gastric ulcer in a prospective multicenter randomized controlled trial.


METHODS
In 43 hospitals 171 intention-to-treat (ITT) patients, diagnosed as having gastric ulcer by endoscopy, were randomly allocated to receive either enprostil 25microg b.i.d. and cimetidine 400mg b.i.d. (Group E=85), or cimetidine 400mg b.i.d. alone (Group C=86) for 8 weeks. Healing was examined by endoscopy at 4 and 8 weeks.


RESULTS
Per protocol (PP) analysis comprised 166 patients (E=82, C=84). Despite no significant advantage at 4 weeks (E=55.3%, C=42.2%), the combination yielded higher healing rates at 8 weeks by ITT (E=89.4%, C=68.6%; p<0.001) and PP analysis (E=92.7%, C=70.2%; p<0.001). Symptom relief rates [E, C] at 2, 4, and 8 weeks were [80.2%, 68.3%] (not significant), [97.4%, 88.3%] (p<0.05), and [95.6%, 87.0%] (p<0.05), respectively. Significant advantage was observed in the patients aged 40 or older, with solitary ulcer (>5mm in diameter), and without smoking or drinking habits. No adverse effects were critical.


CONCLUSIONS
Enprostil safely and significantly augmented gastric ulcer healing and symptom relief by cimetidine.
Murata
Hiroaki
H
Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Japan.
Kawano
Sunao
S
Tsuji
Shingo
S
Tsujii
Masahiko
M
Hori
Masatsugu
M
Kamada
Takenobu
T
Matsuzawa
Yuuji
Y
Katsu
Kenichi
K
Inoue
Kyouichi
K
Kobayashi
Kenichi
K
Mitsufuji
Syouji
S
Bamba
Tadao
T
Kawasaki
Hironaka
H
Kajiyama
Goro
G
Umegaki
Euji
E
Inoue
Masanori
M
Saito
Ichimonji
I
D000328:Adult; D000368:Aged; D002927:Cimetidine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D016620:Enprostil / Q000008:administration & dosage*; D005260:Female; D005500:Follow-Up Studies; D005753:Gastric Mucosa / Q000473:pathology; D005773:Gastroscopy; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D011336:Probability; D011446:Prospective Studies; D012008:Recurrence; D018570:Risk Assessment; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D013276:Stomach Ulcer / Q000188:drug therapy* / Q000473:pathology*; D016896:Treatment Outcome
D002927:Cimetidine; D016620:Enprostil