Quadruple Therapy Using a 3-in-1 Capsule of Bismuth Subcitrate Potassium, Metronidazole, and Tetracycline with Omeprazole Compared to Triple Therapy for the Eradication of Helicobacter pylori: 2010 Presidential Poster

Abstract

Purpose: Although proton pump inhibitor triple therapy is recommended as first line treatment of H. pylori, eradication rates <80% have been recently reported. Bismuth containing quadruple therapy is an alternative. The efficacy of these 2 approaches was evaluated by re-analyzing 2 randomized controlled trials (RCTs). Methods: One N. American RCT comparing omeprazole plus a 3-in-1 capsule of bismuth subcitrate potassium, metronidazole, and tetracycline (OBTM) vs. omeprazole, amoxicillin and clarithromycin (OAC) each given for 10 days was combined with a European RCT comparing OBTM (10 days) vs. OAC (7 days). Both RCTs evaluated therapy in patients with upper GI symptoms, positive 13C urea breath test (UBT), a rapid urease test with at least 1 positive test from histology and culture. H. pylori eradication was confirmed by 2 negative UBTs 6 and 10 weeks post therapy. The impact of sex, age, race, presence of peptic ulcer disease (PUD), duration of OAC therapy, and pretreatment H. pylori clarithromycin and metronidazole resistance was evaluated on efficacy in univariate and multivariate analyses. All data were analyzed on an intention to treat basis. Results: 299 patients were enrolled in the N. American RCT with eradication rates in OBMT arm of 126/147 (86%; 95% CI=79%-91%) and 122/152 (80%; 95% CI=73%-86%) in OAC arm. 440 patients were enrolled in the European RCT with eradication rates of 174/218 (80%; 95% CI=74%-85%) with 10d OBTM and 123/222 (55%; 95% CI=49%-62%) with 7d OAC. There were no predictors of treatment failure in OBTM arms in univariate or multivariate analysis including H. pylori metronidazole resistant strains (81% versus 86%, p=0.23). OAC was less successful in patients without PUD vs. those with PUD (eradication rate 60% vs. 77% respectively; p=0.003), in those taking 7d vs. 10d of therapy (80% vs. 55%; p<0.0001) and in clarithromycin resistant strains (12% vs. 78%, p<0.0001). These factors remained significant in a logistic regression model adjusting for all factors outlined above. In a logistic regression model combining OBTM and OAC groups adjusting for all factors plus an interaction term for clarithromycin resistance and treatment regimen, clarithromycin resistance (p=0.004) was an independent predictor of treatment failure whereas therapy with OBTM was an independent predictor of treatment success (p=0.003). Conclusion: OBTM appears less susceptible to influence of H. pylori resistance to antibiotics and other factors in determining efficacy and overall may be a better first line choice in the treatment of H. pylori infection. Disclosure: Dr Moayyedi, Advisory Board Member, Axcan Pharma; Dr Bazzolo, Advisory Board Member, Axcan Pharma; Prof Megraud, Advisory Board Member and Dr Giguere, Employee, Axcan Pharma. This research was supported by an industry grant from Axcan Pharma.