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

Gastritis With H. Pylori Infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00162877
• Other study ID #: 920505
• Secondary ID: NTUH93S060
• Status: Active, not recruiting
• Phase: N/A
• First received: September 12, 2005
• Last updated: November 22, 2005
• Start date: June 2004
• Est. completion date: April 2005

Study information

• Verified date: January 2004
• Source: National Taiwan University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Taiwan: Department of Health
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 80
• Est. completion date: April 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Communicable Diseases
• Gastritis With H. Pylori Infection
• Helicobacter Infections
• Infection
• Peptic Ulcer
• Peptic Ulcer With H. Pylori Infection

Intervention

Drug:
• Rabeprazole vs. Esomeprazole

Locations

Country	Name	City	State
Taiwan	Department of Internal Medicine, National Taiwan University Hospital	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
National Taiwan University Hospital

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	the role of CYP2C19 on the eradication of H. pylori infection
Secondary	implication of PK/PD relationships