Pharmacogenetics of Gastrointestinal Bleeding

This study has been completed.
Sponsor:
Information provided by:
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT00190255
First received: September 13, 2005
Last updated: May 9, 2011
Last verified: March 2007
  Purpose

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.


Condition Intervention Phase
Gastrointestinal Hemorrhage
Stomach Ulcer
Non-steroidal Anti-inflammatory Drug Sensitivity
Procedure: CY2PC9 genotyping
Phase 4

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Pharmacogenetics of Gastrointestinal Bleeding Under Nonsteroidal Anti-inflammatory Drugs : the Role of Cytochrome P450 2C9

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Biospecimen Retention:   Samples With DNA

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.


Enrollment: 200
Study Start Date: April 2004
Study Completion Date: July 2007
Primary Completion Date: July 2007 (Final data collection date for primary outcome measure)
Intervention Details:
    Procedure: CY2PC9 genotyping
    CY2PC9 genotyping
    Other Name: CY2PC9 genotyping
Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

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
Criteria

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
  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: NCT00190255

Locations
France
Service d'hépato-gastroentérologie, Hôpital Saint Antoine
Paris, France, 75012
: Service d'hépato-gastroentérologie, Hôpital Henri Mondor
Paris, France, 94010
Service d'hépato-gastroentérologie, Hôpital Pitié Salpétrière
Paris, France, 75013
Service d'hépato-gastroentérologie, Hôpital Paul BROUSSE
Villejuif, France, 94804
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Nicolas CARBONNELL, MD Assistance Publique - Hôpitaux de Paris
Study Director: Laurent BECQUEMONT, MD Assistance Publique - Hôpitaux de Paris
  More Information

Publications:
Responsible Party: Christophe AUCAN, Department Clinical Research of developpement
ClinicalTrials.gov Identifier: NCT00190255     History of Changes
Other Study ID Numbers: P030412
Study First Received: September 13, 2005
Last Updated: May 9, 2011
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
gastrointestinal haemorrhage
stomach ulcer
anti-inflammatory agents, non-steroidal
CYP2C9 protein, human
genotype
pharmacogenetics

Additional relevant MeSH terms:
Gastrointestinal Hemorrhage
Hemorrhage
Stomach Ulcer
Ulcer
Gastrointestinal Diseases
Digestive System Diseases
Pathologic Processes
Peptic Ulcer
Stomach Diseases
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Therapeutic Uses
Pharmacologic Actions
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on August 28, 2014