The Role of CYP2C19 on the Eradication of H. Pylori Infection:Implication of PK/PD Relationships

The Role of CYP2C19 Poor Metabolizers and Extensive Metabolizers of PPI in Short-Term Triple Therapy on the Eradication of H. Pylori Infection: Implication of PK/PD Relationships

The objective of this trial is to find the rationale and the optimal dose and duration of regimen for the eradication of H. pylori infection using different proton pump inhibitors.

Study Overview

• Status: Unknown
• Conditions: Peptic Ulcer With H. Pylori Infection; Gastritis With H. Pylori Infection
• Intervention / Treatment: Drug: Rabeprazole vs. Esomeprazole

Detailed Description

Helicobacter pylori in known to be closely associated with the pathogenesis of gastroduodenal disorders such as peptide ulcer. Eradication of this bacterium is important in the treatment of these diseases as well as in the reduction of the recurrence. The one-week triple therapy with proton pump inhibitors (PPIs) is now considered to be the standard therapies in the treatment of Helicobacter pylori infection, providing more than 80% eradication rates with few adverse effects. PPIs are mainly metabolized by CYP2C19, which is known to exhibit polymorphisms in both its genotype and phenotype. Based on the PK/PD results of our study on PPI, recently, we have proposed that CYP2C19 poor metabolizers might be subject to advantageous conditions, especially after day-4, for the treatment of H. pylori infection when 20 mg rabeprazole was given twice daily. Our results also suggest a possibility to start the triple therapy on day-4 of rabeprazole treatment to ensure the optimal acid suppression effect for antibiotics to exert the bacteriocidal effect. To find the rationale and the optimal dosing regimen for the eradication of H. pylori infection using different proton pump inhibitors, volunteers of four groups would be included in this study. PPI (rabeprazole or esomeprazole) is given for 7 days. Antibiotics are given starting from day-1 or day-4 of PPI dosing. The eradication rate of H. pylori infection and the PK/PD of PPIs are also evaluated.

• Study Type: Interventional
• Enrollment: 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 100
    • Department of Internal Medicine, National Taiwan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female dyspeptic patients with H. pylori-positive peptic ulcer or gastritis will be recruited at the university hospital in this study.

Exclusion Criteria:

• 1)Pregnant or lactating female;*2)Patients have endoscopy-based evidence of gastric malignancy, pyloric obstruction, and esophageal stricture requiring dilation, fresh clot, active bleeding, or perforated ulcers;3)Patients requiring anticoagulants or corticosteroid therapy (at dosages greater than the equivalent of prednisone, 10 mg/day);4)Patients with significant impairment of renal function (creatinine>2mg/dl); liver function impairment (AST and ALT 2x upper limit of normal); severe cardiac disease, e.g. angina pectoris, myocardial infarction, cardiac arrhythmia, congestive heart failure (New York Heart Association Functional Classification III and IV) or acute respiratory disease;5)Patients with a history of esophageal and/or gastric varices;6)Use of other investigational drugs within 30 days prior to the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
the role of CYP2C19 on the eradication of H. pylori infection

Secondary Outcome Measures

Outcome Measure
implication of PK/PD relationships

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Principal Investigator: Jyh-Chin Yang, M.D., Department of Internal Medicine, National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start: June 1, 2004
• Study Completion: April 1, 2005

Study Registration Dates

• First Submitted: September 12, 2005
• First Submitted That Met QC Criteria: September 12, 2005
• First Posted (Estimate): September 13, 2005

Study Record Updates

• Last Update Posted (Estimate): November 23, 2005
• Last Update Submitted That Met QC Criteria: November 22, 2005
• Last Verified: January 1, 2004

More Information

Terms related to this study

• Keywords: rabeprazole, omeprazole, CYP2C19, H. pylori, PK/PD
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Disease Attributes; Gastrointestinal Diseases; Stomach Diseases; Gastroenteritis; Intestinal Diseases; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Duodenal Diseases; Gastritis; Infections; Communicable Diseases; Helicobacter Infections; Peptic Ulcer; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Rabeprazole; Esomeprazole
• Other Study ID Numbers: 920505; NTUH93S060