Efficacies of Hybrid and High-dose Dual Therapies for the First-line Anti-H Pylori Treatment
Condition: Helicobacter Pylori Infection
Study type: Interventional

Summary: 
      Both hybrid and high-dose dual therapies developed by the scholars from Taiwan can achieve a
      high eradication rate for clarithromycin-resistant strains, and have a great potential to
      replace bismuth quadruple therapy in the treatment of H. pylori infection. This study aims to
      better understand the potential of both hybrid and igh-dose dual therapies in the treatment
      of H. pylori infection.

      .
    

Detailed description: 
      Helicobacter pylori (H. pylori) infect more than 50% of humans globally. It is the principal
      cause of chronic gastritis, gastric ulcer, duodenal ulcer, gastric adenocarcinoma and gastric
      mucosa-associated lymphoid tissue lymphoma (MALToma). The Real-world Practice & Expectation
      of Asia-Pacific Physicians and Patients in H. pylori Eradication (REAP-HP) Survey
      demonstrated that standard triple therapy was still the most commonly used anti-H. pylori
      regimen in the Asia Pacific region. However, the eradication rates of standard triple therapy
      have declined to less than 80% in most countries worldwide. The main reasons for eradication
      failure of standard triple therapy include antibiotic resistance, poor compliance and CYP2C19
      genotype of host. Clarithromycin resistance of H. pylori has been identified as the main
      reason for the failure of standard triple therapy. Pooled data from 20 studies involving
      1,975 patients treated with standard triple therapy showed an eradication rate of 88% in
      clarithromycin-sensitive strains versus 18% in clarithromycin-resistant strains. Therefore,
      the background rate of clarithromycin resistance is critically important for the efficacy of
      standard triple therapy. Recently, several strategies including bismuth-containing quadruple
      therapy, non-bismuth quadruple therapy (i.e., sequential therapy, concomitant therapy and
      hybrid therapy) and high-dose dual therapy have been proposed to increase the eradication
      rate.

      Hybrid therapy developed by our study group in 2011 consists of a dual therapy with a proton
      pump inhibitor (PPI) and amoxicillin for 7 days followed by a quadruple regimen with a PPI,
      amoxicillin, clarithromycin and metronidazole for 7 days [10]. It achieved an eradication
      rate of 97.4% by intention-to-treat (ITT) analysis and 99.1% by per-protocol (PP) analysis in
      a Taiwan population with clarithromycin resistance rate of 7%. Subsequent randomized
      controlled trials demonstrated that 14-day hybrid therapies were comparable or more effective
      than 10-day sequential therapies. A recent large multicentre randomized controlled trial
      documented that 14-day hybrid and 14-day concomitant therapies had comparable efficacy in the
      treatment of H. pylori infection, and both could cure more than 90% of patients with H.
      pylori infections in areas of high clarithromycin and metronidazole resistance [24].
      Therefore, hybrid therapy has a great potential to replace bismuth quadruple therapy in the
      first-line treatment of H. pylori infection. Currently, hybrid therapy is a recommended
      first-line treatment for H. pylori infection in the ACG guideline

      , Bangkok Consensus Report and Taiwan Consensus Report. High-dose dual therapy developed by
      Yang et al. is another emerging treatment for H pylori infection. The new therapy consists of
      high-dose PPI and amoxicillin, which keep the intragastric pH at a value higher than 6.5
      regardless of CYP2C19 genotype and maintain steady plasma concentration of amoxicillin above
      the minimal inhibitory concentration (MIC) for H pylori [28]. The efficacy of the new therapy
      was significantly higher than that of standard triple therapy in Taiwan. However, it was less
      effective as the first-line therapy for eradicating H pylori in Korea and in the United
      States.

      This study aims to better understand the potential of both hybrid and igh-dose dual therapies
      in the treatment of H. pylori infection.
    

Intervention name(s): Pariet; Amolin; Klaricid; Flagyl
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Rabeprazole 20 mg and amoxicillin 750 mg qid for 14 days; Rabeprazole 20 mg and amoxicillin 750 mg qid for 14 days; Rabeprazole 20 mg and amoxicillin 1 g bid. for 7 days, followed by rabeprazole 20 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg bid. for 7 days; Rabeprazole 20 mg and amoxicillin 1 g bid. for 7 days, followed by rabeprazole 20 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg bid. for 7 days
Other intervention name(s): Rabeprazole; Amoxicillin; Clarithromycin; Metronidazole
Intervention MeSH terms: Amoxicillin; Metronidazole; Clarithromycin; Rabeprazole
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Interventional Study Model
Masking: Single (Investigator)
Primary purpose: Treatment
Keywords: Helicobacter pylori eradication; Hybrid therapy; High dose dual proton pump inhibitor and Amoxicillin therapy