Meta-analysis: Four-Drug, Three-Antibiotic, Non-bismuth-Containing “Concomitant Therapy” Versus Triple Therapy for Helicobacter pylori Eradication


Reprints request to: David Y. Graham, MD, Veterans Affairs Medical Center (111D), 2002 Holcombe Blvd., Houston, Texas 77030, USA. E-mail:


Background: Low success rates with triple therapy for Helicobacter pylori infections have prompted search for alternatives. In one, a proton-pump inhibitor (PPI) and amoxicillin was followed by the PPI plus clarithromycin and a nitroimidazole (sequential therapy); in another, these four drugs were given concomitantly (concomitant therapy).

Aim: To compare concomitant therapy with standard triple therapy for H. pylori infection.

Methods: By searching PubMed, EMBASE, the Cochrane Central Register of Controlled Trials and abstracts of major gastrointestinal meeting, two independent reviewers systemically identified randomized controlled trials (RCT) comparing concomitant quadruple to standard triple therapies as well as studies reporting eradication rates of concomitant quadruple therapy in treatment of H. pylori. Pooled eradication rates and odds ratios (OR) with 95% confidence intervals (CI) were calculated, and univariable metaregression analysis for all extracted variables was conducted.

Results: We identified nine studies (10 treatment arms) including five qualifying RCTs (576 subjects) comparing concomitant (293 subjects, duration 3 to 5 days) and triple therapy (283 subjects, duration 5 to 10 days) and four other studies evaluating concomitant therapy (478 subjects, duration 3 to 7 days). Pooled estimates of the five RCTs showed superiority of concomitant therapy over triple therapy; with intention-to-treat) pooled OR of 2.86 (95% CI: 1.73–4.73) and per-protocol (PP) pooled OR of 3.52 (95% CI: 1.95–6.38). Considering all 10 treatment arms, the ITT eradication rate was 89.7% (95% CI: 86.8–92.1%) and PP was 92.9% (95% CI: 90.2–94.8%).

Conclusion: Concomitant therapy appears to be an effective alternative to triple therapy and is less complex than sequential therapy.