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


Triple therapy eradicated H. pylori infection better than dual therapy

ACP J Club. 1996 May-June;124:65. doi:10.7326/ACPJC-1996-124-3-065

Source Citation

Thijs JC, van Zwet AA, Moolenaar W, Wolfhagen MJ, ten Bokkel Huinink J. Triple therapy vs. amoxicillin plus omeprazole for treatment of Helicobacter pylori infection: a multicenter, prospective, randomized, controlled study of efficacy and side effects. Am J Gastroenterol. 1996 Jan;91:93-7.



To assess the effectiveness and safety of triple antibiotic therapy compared with dual therapy (omeprazole and amoxicillin) in patients with Helicobacter pylori infection.


Randomized controlled trial with 6-week follow-up.


The Netherlands.


118 patients (mean age 53 y, 64% men) who had peptic ulcer disease or non-ulcer dyspepsia and endoscopically proven H. pylori infection. Exclusion criteria were gastric surgery, gastric malignancy, major disease, pregnancy, or allergy to study medications. Complete evaluation at 6 weeks was done in 94% of patients.


Patients were allocated to triple therapy (n = 55) or dual therapy (n = 63). Triple therapy consisted of colloidal bismuth subcitrate, 120 mg 4 times/d; metronidazole, 250 mg 4 times/d; and tetracycline, 250 mg 4 times/d. Dual therapy consisted of omeprazole, 40 mg twice daily, and amoxicillin, 1000 mg twice daily. Both regimens were taken for 14 days. Compliance was self-reported.

Main Outcome Measures

Biopsy- or urea breath test-confirmed eradication of H. pylori and side effects.

Main Results

Both efficacy and intention-to-treat analyses were done. For the intention-to-treat analysis, 14 days of triple therapy led to a higher rate of H. pylori eradication than did dual therapy (95% vs 70%, P = 0.001). {This absolute risk improvement of 25% means that 4 patients would need to receive triple therapy for 14 days (rather than dual therapy) to eradicate H. pylori infection in 1 additional patient, 95% CI 3 to 9; the relative risk improvement was 35%, CI 15% to 65%.}* Side effects were mostly rated as mild by patients in both groups. Patients who received triple therapy had more side effects than patients who received dual therapy (73% vs 51%, P < 0.05). Compliance with medication in the intention-to-treat analysis exceeded 95%.


Triple therapy with bismuth subcitrate, tetracycline, and metronidazole was more effective than dual therapy with omeprazole and amoxicillin for eradicating Helicobacter pylori infection but caused more adverse effects.

Source of funding: Not stated.

For article reprint: Dr. J.C. Thijs, Department of Internal Medicine, Bethesda Hospital, Dr G.H. Amshoffweg 1, 7909 AA Hoogeveen, the Netherlands. FAX 31-528-286-299.

*Numbers calculated from data in article.


Quadruple therapy eradicated H. pylori-associated peptic ulcer disease better than dual therapy

The deluge of new information about H. pylori can be as confusing as it is enlightening. Although there is no single "right answer" about H. pylori eradication, several regimens consistently provide eradication rates of 90% or more. The relative importance of cost, side effects, and compliance will guide the individualized choice of an antibiotic regimen.

The 2 studies by Thijs and colleagues and de Boer and colleagues compare dual therapy (omeprazole and amoxicillin) with triple antibiotic regimens in well-designed, randomized, controlled trials. Both studies showed that dual therapy produced H. pylori eradication rates of less than 80% compared with the greater than 90% eradication rate with triple antibiotic regimens. Although the preponderance of evidence (1, 2) shows that dual therapy has low eradication rates of 50% to 70%, dual therapy is still popular because of lower side effects and simpler (twice daily) dosing regimens. The "take home" point of this commentary: Standard dual therapy with amoxicillin and omeprazole is not recommended because H. pylori eradication rates are too low (1).

Compliance in these 2 studies was outstanding and may not be easily replicated in a non-research setting. Shorter regimens, however, cause fewer side effects or require only twice daily dosing, which would probably improve compliance. In the study of quadruple therapy (triple antibiotics with omeprazole) by de Boer and colleagues, antibiotic treatment was shortened to 7 days without decreasing efficacy and is a reasonable choice. 7-day triple therapy (omeprazole, 20 mg twice daily; clarithromycin, 500 mg twice daily; and amoxicillin, 1 g twice daily, or metronidazole, 500 mg twice daily) appears to provide eradication rates of 90% with fewer side effects and simpler dosing than standard triple antibiotic regimens (2). Studies on these new regimens, however, are mostly limited to small, single- center, randomized, controlled trials. Stronger endorsements may require larger, multicenter trials. Also, these new regimens are more expensive than standard triple antibiotic therapy. With a compliant patient in a cost-sensitive, managed-care setting, standard triple antibiotic therapy may still be the best choice.

Several additional caveats about H. pylori management deserve mention. Currently, the treatment of H. pylori gastritis and non-ulcer dyspepsia is not recommended (3). Further research, however, may identify a subgroup of patients who consistently improve with treatment. Given 90% eradication rates with these antibiotic regimens, laboratory confirmation of H. pylori eradication is only recommended for bleeding, perforated, or refractory ulcers (1, 3). 7-day dual antibiotic and omeprazole regimens may heal active ulcers as well as standard acid suppression therapy. Until more definitive, large-scale trial results are published, however, we recommend continuing standard acid suppression therapy for a total of 6 weeks after completing antibiotic treatment regimen for active ulcers.

Finally, given the multiplicity of antibiotic regimens available, we believe that compliance is improved and confusion minimized by standardizing one's practice: Select 1 or 2 regimens, provide detailed written instructions about how to take the medication, and consider using nurse-educators to explain the rationale for antibiotic regimens and the importance of taking all medications. These steps will replicate the interventions that helped Thijs and colleagues and de Boer and colleagues attain exceptional compliance rates.

Philip S. Schoenfeld, MD, MSEd
James A. Butler, MDNational Naval Medical CenterBethesda, Maryland, USA


1. Soll AH. Medical treatment of peptic ulcer disease. JAMA. 1996;275:622-9.

2. Rauws EA, van der Hulst RW. Current guidelines for the eradication of Helicobacter pylori in peptic ulcer disease. Drugs. 1995;50:984-90.

3. Helicobacter pylori in peptic ulcer disease. NIH Consensus Development Panel on Helicobacter pylori in Peptic Ulcer Disease. JAMA. 1994;272:65-9.