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Tailored Treatment of H. Pylori Infection Based Polymorphisms of CYP2C19 and 23S rRNA of H. Pylori

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2005 by Hamamatsu University.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Yokoyama Foundation for Clinical Pharmacology
Information provided by:
Hamamatsu University
ClinicalTrials.gov Identifier:
NCT00149084
First received: September 6, 2005
Last updated: September 8, 2006
Last verified: September 2005
  Purpose

The eradication rate of the standard H. pylori eradication therapy (such as the triple therapy with a proton pump inhibitor [PPI], amoxicillin and clarithromycin) depends on bacterial susceptibility to clarithromycin and genotypes of CYP2C19 in patients. The investigators intend to investigate whether the tailored therapy based on the two above-mentioned factors increases the cure rate of the initial eradication therapy.


Condition Intervention Phase
Helicobacter Infections
Gastritis
Gastric Ulcer
Duodenal Ulcer
Drug: Lansoprazole, clarithromycin, amoxicillin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pharmacogenomics-Based Tailor-Made Strategy for Eradication of Helicobacter Pylori

Resource links provided by NLM:


Further study details as provided by Hamamatsu University:

Primary Outcome Measures:
  • Whether the tailored treatment yields a higher eradication rate in comparison with the standard treatment

Secondary Outcome Measures:
  • Cost-effectiveness of the tailored strategy

Estimated Enrollment: 296
Study Start Date: April 2003
Detailed Description:

Current treatment strategies for the eradication of H. pylori include a proton pump inhibitor (PPI) and one or two anti-bacterial agents, such as amoxicillin, clarithromycin, and metronidazole.

PPIs, such as lansoprazole and omeprazole, are mainly metabolized in the liver by a genetically determined enzyme, S-mephenytoin 4'-hydroxylase (CYP2C19). Plasma concentrations of PPIs and their activity for acid inhibition depend to a significant extent on the genetic differences in the activity of this enzyme. The acid inhibition attained by the standard dose of a PPI is sometimes therapeutically insufficient in individuals with the rapid extensive metabolizer (RM) genotype of CYP2C19, whereas that in individuals with poor metabolizer (PM) genotype of CYP2C19 is in most cases clinically sufficient. We have reported that the CYP2C19 genotype status is one of the determinants of H. pylori eradication therapy. In the triple therapy with a PPI, amoxicillin, and clarithromycin, bacterial susceptibility to clarithromycin as well as the CYP2C19 genotype status was significantly related to eradication rates of H. pylori. Therefore, the tailored treatment based on these two factors is expected to increase the eradication rates of the initial therapy.

Interestingly, both of CYP2C19 genotypes and bacterial susceptibility to clarithromycin can be measured by the genetic test of the single nucleotide polymorphisms (SNPs) of the CYP2C19 gene and the 23S rRNA gene of H. pylori, respectively. We have recently developed the inexpensive and reliable high-throughput method for measurement of such SNPs by the invader assay. Polymorphisms of CYP2C19 of patients and mutations of 23S rRNA of H. pylori associated with susceptibility to clarithromycin can be detected from the gastric tissue samples infected with H. pylori, such as the gastric tissue sample already used for rapid urease test (RUT).

Then, we treat H. pylori-positive patients by the tailored regimen based on genotypes of CYP2C19 of patients and 23S rRNA of H. pylori or the standard regimen and test the therapeutic efficacy of this pharmacogenomics-based tailored strategy in a prospective manner.

Patients were randomly assigned to the standard or tailored regimen group with the use of a computer-generated randomization list based on a blocked randomization method.

Patients assigned to the standard regimen group were treated with 30 mg of lansoprazole bid, 400 mg of clarithromycin bid, and 750 mg of amoxicillin bid for one week, which had been approved under the Japanese formulary regulation regardless of any pharmacogenomic backgrounds of H. pylori-infected peptic ulcer patients.

In the tailored regimen group, patients infected with a clarithromycin-sensitive strain of H. pylori are treated with triple therapy consisting of clarithromycin 200 mg tid, amoxicillin 500 mg tid and the individualized doses of lansoprazole dose (i.e., 30 mg tid in RMs, 15 mg tid in IMs, and 15 mg bid in PMs) for one week, while patients infected with a clarithromycin-resistant strain of H. pylori are treated with dual therapy consisting of amoxicillin 500 mg qid and the individualzed dose of lansoprazole (i.e., 30 mg qid in RMs, 15 mg qid in IMs, and 15 mg bid in PMs) for two weeks.

  Eligibility

Ages Eligible for Study:   15 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with H. pylori infection

Exclusion Criteria:

  • Patients without H. pylori infection
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00149084

Contacts
Contact: Takahisa Furuta, MD PhD 81-53-435-2850 furuta@hama-med.ac.jp
Contact: Naohito Shirai, MD, PhD naohito@hama-med.ac.jp

Locations
Japan
Hamamatsu University School of Medicine Recruiting
Hamamatsu, Shizuoka, Japan, 431-3192
Contact: Takahisa Furuta, MD, PhD    81-53-435-2850    furuta@hama-med.ac.jp   
Principal Investigator: Takahisa Furuta, MD, PhD         
Sponsors and Collaborators
Hamamatsu University
Yokoyama Foundation for Clinical Pharmacology
Investigators
Study Chair: Takahisa Furuta, MD, PhD Center for Clinical Research, Hamamatsu University School of Medicine
  More Information

Publications:

ClinicalTrials.gov Identifier: NCT00149084     History of Changes
Other Study ID Numbers: Hp.CYP.001
Study First Received: September 6, 2005
Last Updated: September 8, 2006
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by Hamamatsu University:
The tailored H. pylori eradication therapy
CYP2C19 genotype
23S rRNA
clarithromycin
Lansoprazole
Amoxicillin
H. pylori infection

Additional relevant MeSH terms:
Communicable Diseases
Duodenal Ulcer
Helicobacter Infections
Infection
Stomach Ulcer
Ulcer
Bacterial Infections
Digestive System Diseases
Duodenal Diseases
Gastrointestinal Diseases
Gram-Negative Bacterial Infections
Intestinal Diseases
Pathologic Processes
Peptic Ulcer
Stomach Diseases
Amoxicillin
Clarithromycin
Dexlansoprazole
Lansoprazole
Anti-Bacterial Agents
Anti-Infective Agents
Anti-Ulcer Agents
Enzyme Inhibitors
Gastrointestinal Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Synthesis Inhibitors
Proton Pump Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 23, 2014