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


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

ACP J Club. 1996 May-June;124:64. doi:10.7326/ACPJC-1996-124-3-064

Source Citation

de Boer WA, Driessen WM, Jansz AR, Tytgat GN. Quadruple therapy compared with dual therapy for eradication of Helicobacter pylori in ulcer patients: results of a randomized prospective single-centre study. Eur J Gastroenterol Hepatol. 1995 Dec;7: 1189-94.



To assess the effectiveness and side effects of 7-day quadruple therapy (omeprazole and triple antibiotics) compared with 14-day dual therapy (omeprazole and amoxicillin) in the eradication of Helicobacter pylori.


Randomized controlled trial with 6-week follow-up.


Community hospital in the Netherlands.


76 patients (mean age 51 y, 71% men) who had chronic peptic ulcer disease and endoscopically proven H. pylori infection. Exclusion criteria were pregnancy, plans for pregnancy, or allergy to penicillin. Follow-up was 96%.


Patients were allocated to quadruple therapy (n = 40) or dual therapy (n = 36). Quadruple therapy consisted of omeprazole, 20 mg twice daily, on days 1 to 10; colloidal bismuth subcitrate, 120 mg 4 times/d, on days 4 to 10; tetracycline hydrochloride, 500 mg 4 times/d, on days 4 to 10; and metronidazole, 500 mg 3 times/d, on days 4 to 10. Dual therapy consisted of omeprazole, 20 mg twice daily, on days 1 to 14 and amoxicillin, 1000 mg twice daily, on days 1 to 14. Acid-suppressive medication and H2-receptor antagonists were prohibited. Patients recorded side effects and tolerability with the regimens. Compliance was assessed by pill count.

Main Outcome Measures

Biopsy-confirmed eradication of H. pylori and side effects.

Main Results

7 days of quadruple therapy led to a higher cure rate 6 weeks after treatment than did 14 days of dual therapy (93% vs 56%, P < 0.001) by intention-to-treat analysis. {This absolute risk improvement of 37% means that 3 patients would need to receive quadruple therapy for 7 days (rather than dual therapy for 14 days) to cure 1 additional patient of peptic ulcer disease, 95% CI 2 to 5; the relative risk improvement was 67%, CI 27% to 136%.}* In a per protocol analysis, the cure rate was 100% in patients who received quadruple therapy compared with 59% of patients who received dual therapy (P < 0.001). Patients who received dual therapy were more likely to report no side effects compared with patients who received quadruple therapy (37% vs 13%, P = 0.026). More than 80% of patients in both groups had 100% compliance with medication regimens.


7-day quadruple therapy was more effective than 14-day dual therapy in curing Helicobacter pylori infection but caused more adverse effects.

Source of funding: None.

For article reprint: Dr. W.A. de Boer, Sint Anna Ziekenhuis, Department of Internal Medicine, Postbus 10, 5340 BE Oss, the Netherlands. FAX 31-412-621-2222.

*Numbers calculated from data in article.


Triple therapy eradicated H. pylori infection 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.