Gastroenterology · Medical Literature
[Dual therapy vs bismuth quadruple therapy in recurrent H. pylori: multicenter randomized trial].
Abstract
With increasing antibiotic resistance, treatment of H. pylori infection has gradually become a challenge for clinicians. To compare the efficacy and safety of dual therapy plus bismuth (DTB) with quadruple therapy with bismuth (DBT) for the treatment of H. pylori in patients with at least one previous eradication therapy failure. The primary objective was eradication of H. pylori at 6 weeks after treatment. Randomized, open-label, superiority clinical trial evaluating H. pylori eradication in patients with at least one prior treatment failure. Participants were randomly assigned to receive a 14-day course of bismuth-based dual therapy (TDB: esomeprazole 40mg three times daily, amoxicillin 1g three times daily, and bismuth subsalicylate 262mg four times daily) or bismuth-based quadruple therapy (TQB: esomeprazole 40mg three times daily, amoxicillin 1g three times daily, doxycycline 100mg twice daily, and bismuth subsalicylate 262mg four times daily). A total of 267 of 283 subjects were randomized; 11 were excluded due to exclusion criteria and 5 declined participations. Eradication rates by intention-to-treat and per-protocol analyses were 90.1% (119/131; 95% CI: 84.7-94.7%) and 95.8% (113/118; 95% CI: 90.5-98.2%) for TDB, and 78.7% (107/136; 95% CI: 71.1-84.7%) and 84.7% (94/111; 95% CI: 76.8-90.2%) for TQB. Superiority of TDB was confirmed (p=0.001 in ITT; p=0.04 in PP). Adverse events occurred in 30.5% (33/131) of TDB patients and 44.1% (60/136) of TQB patients (p=0.001). Bismuth-based dual therapy is a superior alternative to classical bismuth quadruple therapy for the treatment of patients with at least one failed therapy for H. pylori, as it provides greater eradication with superior safety and compliance.
Clinical relevance
Recurrent H. pylori infection following at least one failed eradication attempt represents a growing clinical challenge in the era of rising antibiotic resistance, where standard regimens increasingly fall short. This multicenter randomized trial directly addresses the evidence gap regarding optimal salvage therapy, comparing a novel bismuth-based dual therapy (TDB) against the conventional bismuth quadruple regimen (TQB) in a real-world, treatment-experienced population. Clinicians managing H. pylori salvage cases need updated, evidence-based regimens that balance superior eradication with an acceptable safety and tolerability profile.
Key findings
1. ITT eradication rate for bismuth-based dual therapy (TDB: esomeprazole + amoxicillin + bismuth subsalicylate) was 90.1% (119/131; 95% CI: 84.7–94.7%), significantly superior to TQB at 78.7% (107/136; 95% CI: 71.1–84.7%) (p=0.001). 2. Per-protocol eradication rate for TDB was 95.8% (113/118; 95% CI: 90.5–98.2%) vs. 84.7% (94/111; 95% CI: 76.8–90.2%) for TQB, confirming superiority (p=0.04). 3. Superiority of TDB over TQB was formally confirmed on both ITT and PP analyses, meeting the pre-specified primary endpoint of H. pylori eradication at 6 weeks post-treatment. 4. Adverse event rates were significantly lower in the TDB arm: 30.5% (33/131) vs. 44.1% (60/136) for TQB (p=0.001), indicating a meaningfully better tolerability profile. 5. Both regimens were administered as 14-day courses; TDB consisted of esomeprazole 40 mg TID + amoxicillin 1 g TID + bismuth subsalicylate 262 mg QID, while TQB added doxycycline 100 mg BID. 6. Of 283 enrolled subjects, 267 were randomized (11 excluded per exclusion criteria, 5 declined), reflecting a well-controlled trial design with adequate allocation.
Practice implications
For patients with H. pylori infection and at least one prior eradication failure, bismuth-based dual therapy (esomeprazole 40 mg TID + amoxicillin 1 g TID + bismuth subsalicylate 262 mg QID for 14 days) should be considered as a preferred salvage regimen over bismuth quadruple therapy, given its superior ITT (90.1% vs. 78.7%) and PP (95.8% vs. 84.7%) eradication rates alongside a significantly lower adverse event burden. The addition of doxycycline in the quadruple regimen did not confer additional benefit and was associated with higher adverse event rates, suggesting that antibiotic simplification with high-dose PPI and bismuth may be the more effective and better-tolerated strategy in this population. Clinicians should counsel patients on the intensive dosing schedule (TID/QID) required for TDB adherence, as compliance was reflected in the high per-protocol eradication rates, and confirm local resistance patterns where susceptibility testing is available.