Optimized Nonbismuth Quadruple Therapies Cure Most Patients With Helicobacter pylori Infection in Populations With High Rates of Antibiotic Resistance

Background & Aims Strategies to eradicate Helicobacter pylori infection could be improved by suppressing acid and extending the duration of therapy (optimization). We compared the efficacy of 2 different optimized nonbismuth quadruple regimens in areas of high resistance to antimicrobial agents. Methods We performed a prospective noninferiority multicenter trial in which 343 consecutive individuals with H pylori infection were assigned randomly to groups given hybrid therapy (40 mg omeprazole and 1 g amoxicillin, twice daily for 14 days; 500 mg clarithromycin and 500 mg nitroimidazole were added, twice daily for the final 7 days) or concomitant therapy (same 4 drugs taken concurrently, twice daily for 14 days). We assessed bacterial resistance to these drugs in a subset of patients using the E-test. Efficacy, side effects, and compliance were determined. Results In per-protocol analysis, rates of eradication for hybrid and concomitant therapies were 92% (95% confidence interval [CI], 87%−95%) and 96.1% (95% CI, 93%–99%), respectively ( P  = .07). In intention-to-treat analysis, rates were 90% (95% CI, 86%−93%) and 91.7% (95% CI, 87%–95%), respectively ( P  = .35). Almost all patients (95.5%) were fully compliant; 23.5% of patients had  H pylori strains that were resistant to clarithromycin (Italy, 26%; Spain, 19.5%), 33% were resistant to metronidazole (Italy, 33%; Spain, 34%), and 8.8% were resistant to both drugs (Italy, 7.1%; Spain, 11.5%). Side effects (only mild) were reported in 51.5% of patients (47% hybrid vs 56% concomitant; P  = .06). Compliance greater than 80% was the only significant predictor of eradication (odds ratio, 12.5; 95% CI, 3.1−52; P  = .001). Significantly more patients were compliant with hybrid therapy (98.8%) than concomitant therapy (95.2%;  P  = .05). Conclusions Optimized nonbismuth quadruple hybrid and concomitant therapies cured more than 90% of patients with H pylori infections in areas of high clarithromycin and metronidazole resistance. ClinicalTrials.gov number NCT01464060.