Tailored Treatment of H. Pylori Infection Based Polymorphisms of CYP2C19 and 23S rRNA of H. Pylori
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00149084|
Recruitment Status : Unknown
Verified September 2005 by Hamamatsu University.
Recruitment status was: Recruiting
First Posted : September 8, 2005
Last Update Posted : September 11, 2006
|First Submitted Date ICMJE||September 6, 2005|
|First Posted Date ICMJE||September 8, 2005|
|Last Update Posted Date||September 11, 2006|
|Study Start Date ICMJE||April 2003|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
||Whether the tailored treatment yields a higher eradication rate in comparison with the standard treatment|
|Original Primary Outcome Measures ICMJE
||Whether the tailored treatment yield higher eradication rate in comparison with the standard treatment.|
|Change History||Complete list of historical versions of study NCT00149084 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||Cost-effectiveness of the tailored strategy|
|Original Secondary Outcome Measures ICMJE
||cost-effective ness of the tailored strategy.|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Tailored Treatment of H. Pylori Infection Based Polymorphisms of CYP2C19 and 23S rRNA of H. Pylori|
|Official Title ICMJE||Pharmacogenomics-Based Tailor-Made Strategy for Eradication of Helicobacter Pylori|
|Brief Summary||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.|
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.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 3|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Intervention ICMJE||Drug: Lansoprazole, clarithromycin, amoxicillin|
|Study Arms||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Unknown status|
|Original Enrollment ICMJE||Not Provided|
|Study Completion Date||Not Provided|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages||15 Years to 90 Years (Child, Adult, Older Adult)|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||Japan|
|Removed Location Countries|
|NCT Number ICMJE||NCT00149084|
|Other Study ID Numbers ICMJE||Hp.CYP.001|
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||Hamamatsu University|
|Collaborators ICMJE||Yokoyama Foundation for Clinical Pharmacology|
|PRS Account||Hamamatsu University|
|Verification Date||September 2005|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP