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Updated: Sep 16, 2025
Quadruple-Checkerboard: A Modification of the Three-Dimensional Checkerboard for Studying Drug Combinations
Published on: July 24, 2021
Effectiveness and Safety of First-Line Non-Bismuth Quadruple Concomitant Therapy Versus Single-Capsule Bismuth
Olga P Nyssen1, Nuria Montes2, Ángeles Pérez-Aísa3
1Department of Gastroenterology, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain.
Background:
The V Spanish Consensus Conference on Helicobacter pylori recommended either a 14-day non-bismuth quadruple concomitant therapy (CT: proton pump inhibitor [PPI], clarithromycin, amoxicillin, and metronidazole) or a 10-day bismuth-containing quadruple therapy (Sc-BQT: PPI, bismuth, tetracycline, and metronidazole in a single capsule). The relative advantages of each remain uncertain.
Aim:
To compare the effectiveness and safety of first-line empirical CT versus Sc-BQT in Spain.
Methods:
We analysed data from treatment-naïve patients enrolled in the European Registry on H. pylori Management (Hp-EuReg; 2013-2024). Multivariate logistic regression with propensity score weighting and bootstrap analysis (10,000 replicas) estimated modified intention-to-treat effectiveness and safety.
Results:
We evaluated 13,787 treatments: 7234 (52%) with CT-10 and 14 days, and 6553 (48%) with Sc-BQT-every 6 and 8 h. Sc-BQT showed greater effectiveness than 14-day CT (94% vs. 91%; p < 0.001). However, 14-day CT with standard-dose PPI (93%) outperformed Sc-BQT every 6 h with low-dose PPI (90%) (p = 0.043). Sc-BQT every 8 h with high-dose PPI achieved the highest eradication (98%) (p = 0.015). Adherence was similar with Sc-BQT (94%) and 14-day CT (93%), being highly associated with eradication success (p < 0.001). Sc-BQT, particularly with low- or standard-dose PPI, had a better safety profile (p < 0.001).
Conclusion:
Sc-BQT is more effective, better tolerated, and more broadly applicable than 14-day CT. Both regimens achieved ≥ 90% success, but Sc-BQT's stewardship-friendly profile further supports its use as first-line therapy for H. pylori eradication.
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