Pharmacogenetics of Gastrointestinal Bleeding

Gastrointestinal Hemorrhage Clinical Trial

Official title:

Pharmacogenetics of Gastrointestinal Bleeding Under Nonsteroidal Anti-inflammatory Drugs : the Role of Cytochrome P450 2C9

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00190255
• Other study ID #: P030412
• Status: Completed
• Phase: Phase 4
• First received: September 13, 2005
• Last updated: May 9, 2011
• Start date: April 2004
• Est. completion date: July 2007

Study information

• Verified date: March 2007
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Observational

Clinical Trial Summary

Gastrointestinal bleeding is a severe adverse effect occurring in subjects secondary to the use of nonsteroidal anti-inflammatory drugs (NSAIDs). The enzyme CYP2C9 is responsible for the elimination of several NSAIDs. This protein is inactive in 12% of the subjects because of genetic mutations. We hypothesized that individuals carrying such mutations should be at higher risk of gastrointestinal bleeding since they display decreased NSAIDs elimination.

Description:

Gastrointestinal bleeding is a severe adverse effect occurring in subjects secondary to the use of nonsteroidal anti-inflammatory drugs (NSAIDs). The enzyme CYP2C9 is responsible for the elimination of most NSAIDs. Several polymorphisms have been observed in CYP2C9. Of these, the CYP2C9*3 allele, found in 12% of caucasian subjects, leads to reduced function of the enzyme.

We hypothesized that individuals carrying this mutation should be at higher risk of gastrointestinal bleeding since they display decreased elimination of some NSAIDs.

The purpose of this study is to determine whether the frequency for CYP2C9*3 variant allele is increased in subjects using NSAIDs metabolized by CYP2C9 in comparison with subjects under NSAIDs not metabolized by this enzyme.

The study groups consist of 200 patients suffering from gastrointestinal bleeding after NSAIDs use, divided in 100 patients using NSAIDs metabolized by CYP2C9 and 100 patients using other NSAIDs.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: July 2007
• Est. primary completion date: July 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Upper gastrointestinal bleeding revealed by hematemesis, melena or lowering of at least 2g/dl of haemoglobin

• Endoscopic report of gastrointestinal ulcer or haemorrhagic lesion

• Immediate antecedents of NSAID therapy

Exclusion Criteria:

• Cirrhosis (Child B or C)

• Coma

• Concomitant therapy with substrates or inhibitors of CYP2C9 : ketoconazole, itraconazole, ritonavir, phenobarbital, rifampicin, depakine, phenytoin, St John's worts

• Patients treated by a NSAID metabolized by CYP2C9 and a NSAID not metabolized by CYP2C9

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Gastrointestinal Hemorrhage
• Hemorrhage
• Non-steroidal Anti-inflammatory Drug Sensitivity
• Stomach Ulcer

Intervention

Procedure:
• CY2PC9 genotyping
CY2PC9 genotyping

Locations

Country	Name	City	State
France	: Service d'hépato-gastroentérologie, Hôpital Henri Mondor	Paris
France	Service d'hépato-gastroentérologie, Hôpital Pitié Salpétrière	Paris
France	Service d'hépato-gastroentérologie, Hôpital Saint Antoine	Paris
France	Service d'hépato-gastroentérologie, Hôpital Paul BROUSSE	Villejuif

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

References & Publications (2)

Martin JH, Begg EJ, Kennedy MA, Roberts R, Barclay ML. Is cytochrome P450 2C9 genotype associated with NSAID gastric ulceration? Br J Clin Pharmacol. 2001 Jun;51(6):627-30. — View Citation

Martínez C, Blanco G, Ladero JM, García-Martín E, Taxonera C, Gamito FG, Diaz-Rubio M, Agúndez JA. Genetic predisposition to acute gastrointestinal bleeding after NSAIDs use. Br J Pharmacol. 2004 Jan;141(2):205-8. Epub 2004 Jan 5. — View Citation