Bismuth-Based Quadruple Therapy versus Metronidazole-Intensified Triple Therapy as a First-Line Treatment for Clarithromycin-Resistant Helicobacter pylori Infection: A Multicenter Randomized Controlled Trial

Abstract

Background/Aims: Clarithromycin resistance is a main factor for treatment failure in the context of Helicobacter pylori infection. However, the treatment regimen for clarithromycin-resistant H. pylori infection has not yet been determined. We aimed to compare the efficacy and cost-effectiveness of 14-day bismuth-based quadruple therapy versus 14-day metronidazole-intensified triple therapy for clarithromycin-resistant H. pylori infection with genotypic resistance.Methods: This was a multicenter, randomized, controlled trial. A total of 782 patients with H. pylori infection examined using sequencing-based clarithromycin resistance point mutation tests were recruited between December 2018 and October 2020 in four institutions in Korea. Patients with significant point mutations (A2142G, A2142C, A2143G, A2143C, and A2144G) were randomly assigned to receive either 14-day bismuth-based quadruple therapy (n=102) or 14-day metronidazole-intensified triple therapy (n=99). Results:The overall genotypic clarithromycin resistance rate was 25.7% according to the sequencing method. The eradication rate of 14-day bismuth-based quadruple therapy was not significantly different in the intention-to-treat analysis (80.4% vs 69.7%, p=0.079), but was significantly higher than that of 14-day metronidazole-intensified triple therapy in the per-protocol analysis (95.1% vs 76.4%, p=0.001). There were no significant differences in the incidence of side effects. In addition, the 14-day bismuth-based quadruple therapy was more cost-effective than the 14-day metronidazole-intensified triple therapy.Conclusions: Fourteen-day bismuth-based quadruple therapy showed comparable efficacy with 14-day metronidazole-intensified triple therapy, and it was more cost-effective in the context of clarithromycin-resistant H. pylori infection.

Effective Eradication Regimen and Duration According to the Clarithromycin Susceptibility of Helicobacter pylori Determined Using Dual Priming Oligonucleotide-Based Multiplex Polymerase Chain Reaction

“…17,18,20 PP analysis from one recent randomized controlled trial, in Korea, showed that 14-day BQT achieved higher clarithromycinresistant H. pylori eradication than 14-day PAM as a firstline therapy (95.1% vs 76.4%, p=0.001). 21 A study in China, where H. pylori clarithromycin resistance is high, reported that tailored 10-day BQT (as informed by DPO-PCR results) had a higher eradication rate of 93.4%, based on PP analysis. 22 Therefore, in the presence of clarithromycin resistance, BQT appears to be a good alternative treatment option.…”

“…16 However, there may be several factors other than A2142G and A2143G point mutations that affect the eradication rate in the STT group. There is a possibility that other clinically significant point mutations exist, such as A2142C, A2143C, and A2144G, that are not currently detected by DPO-PCR, 21 although these mutations alone are associated with less than 5% of clarithromycin-resistant H. pylori isolates in Korea. 21,27 Due to the common heterogeneity of H. pylori, even within one individual, 28 the tissue biopsy-based DPO-PCR has the inherent potential bias of false-negative results, which may contribute to treatment failures.…”

“…There is a possibility that other clinically significant point mutations exist, such as A2142C, A2143C, and A2144G, that are not currently detected by DPO-PCR, 21 although these mutations alone are associated with less than 5% of clarithromycin-resistant H. pylori isolates in Korea. 21,27 Due to the common heterogeneity of H. pylori, even within one individual, 28 the tissue biopsy-based DPO-PCR has the inherent potential bias of false-negative results, which may contribute to treatment failures. In addition, different individual CYP2C9 polymorphism that affects the proton pump inhibitor metabolism can be considered another cause.…”

Bismuth-Based Quadruple Therapy for Clarithromycin-Resistant Helicobacter pylori Infection: Effectiveness and Cost-Efficiency

“…In the latest issue of Gut and Liver , Seo et al 4 compared both the efficacy and cost-effectiveness of tailored therapy as a first-line treatment using sequencing-based clarithromycin resistance testing. Eradication rates of the 14-day bismuth-based quadruple therapy (BQT) were not significantly different from that of 14-day metronidazole-intensified triple therapy (MIT) in an intention-to-treat analysis (80.4% vs 69.7%, p=0.079), but were significantly higher in the per-protocol analysis (95.1% vs 76.4%, p=0.001).…”

“…In this study, 4 cost-effectiveness analyses of tailored therapy were compared with empirical CTT in first-line and second-line therapies using incremental cost-effectiveness ratio. BQT is more cost-effective than MIT.…”