Current issues of ACP Journal Club are published in Annals of Internal Medicine


Ranitidine and antimicrobial therapy for Helicobacter pylori healed duodenal ulcers faster than ranitidine alone

ACP J Club. 1991 Nov-Dec;115:70. doi:10.7326/ACPJC-1991-115-3-070

Source Citation

Graham DY, Lew GM, Evans DG, Evans DJ Jr, Klein PD. Effect of triple therapy (antibiotics plus bismuth) on duodenal ulcer healing. Ann Intern Med. 1991 Aug 15;115:2 66-9.



To determine whether antibiotic therapy for Helicobacter pylori added to H2-receptor antagonist therapy accelerates the healing of duodenal ulcers.


Randomized, single-blind, controlled trial.


Houston Veterans Affairs Medical Center, from June 1988 to May 1990.


Consecutive patients with endoscopically proven active duodenal ulcer were entered unless they were receiving anti-ulcer therapy, were scheduled for surgery, refused to participate, or had comorbid disease likely to limit follow-up. 98% of patients had H. pylori infection. The 2 study groups were similar for mean ulcer size, the proportion of smokers, recent use of nonsteroidal anti-inflammatory drugs, and alcohol intake ≥ once per week.


Patients received 300 mg/d of ranitidine for 16 weeks, either alone (n = 52) or, as triple therapy, with bismuth, either 5 tablets/d (first 30 patients) or 8 tablets/d (last 23 patients), tetracycline hydrochloride, 500 mg 4 times/d, and metronidazole, 250 mg 3 times/d, all given for the first 2 weeks (n = 53). Endoscopy was done at entry and after 2, 4, 8, 12, and 16 weeks of therapy or until the ulcer healed. Infection with H. pylori was assessed by 13C-urea breath test, by assay of IgG antibody against H. pylori, and by culture and histologic evaluation of antral mucosal biopsy specimen

Main outcome measure

Ulcer healing, defined as complete re-epithelialization. The endoscopist was blinded to treatment allocation.

Main results

Ulcers healed faster in patients receiving ranitidine and triple therapy, as shown by cumulative healing or lifetable analysis (P< 0.01). After 16 weeks, ulcers were healed in 98% of patients receiving ranitidine and triple therapy, and in 84% of those receiving ranitidine alone. 45 of 53 patients who received antibiotics were free of infection at the end of the study, therapy failed in 2, and status was unknown in 6 patients. All patients assigned to ranitidine alone remained infected with H. pylori. 14 of 15 patients receiving nonsteroidal anti-inflammatory drugs during the study had healed ulcers after 16 weeks..


Duodenal ulcers healed faster with ranitidine and antimicrobial therapy for H. pylori than with ranitidine alone.

Sources of funding: Department of Veterans Affairs; National Institute of Diabetes and Digestive and Kidney Diseases; Department of Agriculture; Hilda Schwartz.

Address for article reprint: Dr. D. Y. Graham, Veterans Affairs Medical Center (111D), 2002 Holcombe Boulevard, Houston, TX 77030, USA.


Helicobacter pylori infection is a causative factor in chronic active gastritis, but its role in the etiology of duodenal ulcers is less clear. Graham and colleagues add to the burgeoning mountain of circumstantial evidence for the role of this spiral-shaped bacterium in the pathogenesis of duodenal ulcers.

In this single-blind, randomized controlled study the addition of 3 antimicrobials (tetracycline, metronidazole, and bismuth subsalicylate) to a histamine-receptor (H2) blocker accelerated the healing of duodenal ulcers. This report confirms the almost universal finding of H. pylori infection in patients with duodenal ulcer and shows that eradication of this organism is associated with improved duodenal ulcer healing rates at each possible end point. Lacking, of course, is the other of Koch's postulates, the reproduction of duodenal ulcer disease by the deliberate infection of volunteers with this bacterium; previous attempts to do so yielded gastric lesions, especially in the presence of H2-receptor blocker administration (1).

Treatment of uncomplicated duodenal ulcer disease is unlikely to be altered by these findings. The addition of 15 pills per day—not to mention the cost, inconvenience, and side effects—is likely to limit this regimen to a select group of patients. As the authors point out, the marginal benefit of triple antibiotic therapy is minimal now that safe and effective agents are widely available for the treatment of duodenal ulcers. Further, other studies have shown a high recurrence rate of the bacterium after treatment. Readers should refer to studies (2-5) published after the report of this trial. Antibiotics, through known or unknown mechanisms of action, may be useful in the treatment of that subset of patients with refractory or recurrent duodenal ulcers. We await further studies with baited (13C-urea) breath.

I. David Shocket, MD
Veterans Affairs Medical CenterBoston, Massachusetts


1. Wormsley KG. Campylobacter pylori and ulcer disease—a causal connection? Scand J Gastroenterol. 1989;24 (Suppl 160):53-8.

2. Graham DY, Lew GM, Klein PD, et al. Effect of treatment of Helicobacter pylori infections on the long-term recurrence of gastric or duodenal ulcer. A randomized, controlled study. Ann Intern Med. 1992;116:705-8.

3. Hentschel E, Brandstätter G, Dragosics B, et al. Effect of ranitidine and amoxicillin plus metronidazole on the eradication of Helicobacter pylori and the recurrence of duodenal ulcer. N Engl J Med. 1993;328:308-12.

4. Labenz J, Gyenes E, Rühl GH, Börsch G. Amoxicillin plus omeprazole versus triple therapy for eradication of Helicobacter pylori in duodenal ulcer disease: a prospective, randomized, and controlled study. Gut. 1993;34:1167-70.

5. Veldhuyzen van Zanten SJ, Sherman PM. Helicobacter pylori infection as a cause of gastritis, duodenal ulcer, gastric cancer and nonulcer dyspepsia: a systematic overview. Can Med Assoc J. 1994;150:177-85.