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Pharmacogenetics of Gastrointestinal Bleeding

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ClinicalTrials.gov Identifier: NCT00190255
Recruitment Status : Completed
First Posted : September 19, 2005
Last Update Posted : May 10, 2011
Sponsor:
Information provided by:

Study Description
Brief 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.

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

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.


Study Design

Study Type : Observational
Actual Enrollment : 200 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Pharmacogenetics of Gastrointestinal Bleeding Under Nonsteroidal Anti-inflammatory Drugs : the Role of Cytochrome P450 2C9
Study Start Date : April 2004
Primary Completion Date : July 2007
Study Completion Date : July 2007

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Groups and Cohorts

Intervention Details:
    Procedure: CY2PC9 genotyping
    CY2PC9 genotyping

Outcome Measures

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.

Eligibility Criteria

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00190255


Locations
France
Service d'hépato-gastroentérologie, Hôpital Saint Antoine
Paris, France, 75012
Service d'hépato-gastroentérologie, Hôpital Pitié Salpétrière
Paris, France, 75013
: Service d'hépato-gastroentérologie, Hôpital Henri Mondor
Paris, France, 94010
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
First Posted: September 19, 2005    Key Record Dates
Last Update Posted: May 10, 2011
Last Verified: March 2007

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:
Hemorrhage
Gastrointestinal Hemorrhage
Stomach Ulcer
Pathologic Processes
Gastrointestinal Diseases
Digestive System Diseases
Peptic Ulcer
Duodenal Diseases
Intestinal Diseases
Stomach Diseases
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antirheumatic Agents