High-dose Dual Therapy Is Superior to Standard First-line or Rescue Therapy for Helicobacter pylori Infection

Abstract

Background & Aims The efficacy of treatment of Helicobacter pylori infection has decreased steadily due to increasing resistance to clarithromycin, metronidazole, and levofloxacin. Resistance to amoxicillin is generally low, and high intragastric pH increases the efficacy of amoxicillin, so we investigated whether a combination of a high-dose proton-pump inhibitor and amoxicillin (dual therapy) was more effective than standard first-line or rescue therapies in eradicating H pylori. Methods We performed a large-scale, multi-hospital trial to compare the efficacy of a high-dose dual therapy (HDDT) with that of standard therapies in treatment-naïve (n=450) or treatment-experienced (n=168) patients with H pylori infection. Treatment-naïve patients were randomly assigned to groups given HDDT (rabeprazole 20 mg and amoxicillin 750 mg, 4 times/day for 14 days; group A1), sequential therapy for 10 days (group B1), or clarithromycin-containing triple therapy for 7 days (group C1). Treatment-experienced patients were randomly assigned to groups given HDDT for 14 days (group A2), sequential therapy for 10 days (B2), or levofloxacin-containing triple therapy for 7 days (C2). H pylori infection was detected using the 13C–urea breath test. We evaluated factors associated with treatment outcomes. Results In the intention-to-treat treat analysis, H pylori was eradicated in 95.3% of patients in group A1 (95% confidence interval [CI], 91.9%–98.8%), 85.3% in B1 (95% CI, 79.6%–91.1%), and 80.7% in group C1 (95% CI, 74.3%–87.1%). Infection was eradicated in 89.3% of patients in group A2 (95% CI, 80.9%–97.6%), 51.8% in group B2 (95% CI, 38.3%–65.3%), and 78.6% (95% CI, 67.5%–89.7%). The efficacy of HDDT was significantly higher than that of currently recommended regimens, irrespective of CYP2C19 genotype. Bacterial resistance to drugs was associated with treatment failure. There were no significant differences between groups in adverse events or patient adherence. Conclusions HDDT is superior to standard regimens as empiric first-line or rescue therapy for H pylori infection, with similar safety profiles and tolerability. ClinicalTrials.gov no: NCT01163435.

ACG Clinical Guideline: Treatment of Helicobacter pylori Infection

“…amoxicillin dosing) with other regimens as salvage treatments ( 178,203,206 ). Two of these studies have been conducted in Germany, both by Miehlke et al Th e fi rst study included 84 patients with at least one previous treatment failure (most patients had two or more treatment failures) and compared 14-day high-dose dual therapy (omeprazole 40 mg and amoxicillin 750 mg, both given q.i.d .)…”

“…By proportion meta-analysis, the pooled eradication rate for high-dose dual salvage treatment in the European studies was 71% (63-79%). Finally, in Taiwan, Yang et al ( 206 ) included 168 patients with one or more previous eradication failures, and reported that the eradication rate with the 14-day high-dose dual therapy (rabeprazole 20 mg and amoxicillin 750 mg, both given q.i.d .) was 89% (81-98%), which was not signifi cantly diff erent than with 7-day levofl oxacin triple therapy (79, 67-90%), but was signifi cantly higher than with 10-day sequential therapy (52, 38-65%).…”

“…Only two RCTs have assessed its effi cacy as a salvage treatment, and the results are discouraging. One RCT, conducted in Taiwan, included 168 patients who had failed one or more previous eradication treatments; the eradication rate with 10-day sequential therapy (52%, 95% CI 38-65%) was signifi cantly lower than with 14-day high-dose dual amoxicillin therapy (89%, 81-98%) or 7-day levofl oxacin triple therapy (79, 67-90%) ( 206 ). Th e other RCT was conducted in Korea and included 158 patients who had failed clarithromycin triple therapy; 10-day sequential therapy was signifi cantly inferior to 10-day bismuthbased quadruple therapy (eradication rates 57 vs. 84%) ( 210 ).…”

Gastric Mucosal Atrophy Might Be Associated with the Efficacy of First-Line Therapy Using Vonoprazan for <i>Helicobacter pylori</i>

“…In fact, when the role of high-dose dual therapy (HDDT) with 20 mg RPZ and 750 mg AMPC 4 times per day for 14 days was examined, ITT analysis showed that H. pylori was eradicated in 95.3% of patients in the HDDT group and 81% in the standard triple therapy group [38]. Conversely, a study of the effect of extended dual release LPZ with AMPC had to be discontinued because of a lack of efficacy (53.8% in both ITT and PP analysis) [39].…”

Randomized Controlled Trial for Helicobacter pylori Eradication in a Naive Portuguese Population: Is Sequential Treatment Superior to Triple Therapy in Real World Clinical Setting?

“…14,15,19 Newer treatment options, such as concomitant 25,26 (TT plus metronidazole), hybrid 27,28 (ST, but with amoxicillin added during the second half of the regimen) and dual 29 (high dose PPI plus amoxicillin, four doses daily) treatment have been developed, in order to achieve eradication rates > 90%, as defended by Graham et al, 30 and have shown superior eradication rates compared to TT, but in most of them, TT duration was inferior to 14 days. 26,27,29 Regarding ST, a recent meta-analysis comparing it with hybrid and concomitant therapies showed no efficacy advantage in the newer treatment strategies. 31 Bismuth-based regimens, advocated in the Maastricht IV Consensus as a firstline treatment option in regions with high clarithromycin resistance, 1 has shown favorable results, 32 but bismuth is not widely available in many European countries, in particular in Portugal.…”