Cohort Study of Clopidogrel and Proton Pump Inhibitors

NCT01231867 | Completed DMC

• 2 other identifiers: 09_042CALIBER 09_09
• Study Type: observational
• Target: 24,471
• Locations: 1 country
• Sites: 1

Brief Summary

Patients who have experienced and survived non-ST segment elevation acute coronary syndromes are often prescribed a combination of aspirin and clopidogrel to thin the blood and prevent further acute coronary episodes. Both clopidogrel and aspirin may cause stomach bleeds and so a prophylactic proton pump inhibitor is frequently co-prescribed in order to prevent such bleeds. Recent mechanistic and observational studies suggest proton pump inhibitors may reduce the effectiveness of clopidogrel and so patients may not benefit as much as expected from combined aspirin and clopidogrel. The investigators propose a cohort study of patients prescribed clopidogrel + aspirin. Amongst these patients the investigators will measure the relative rate of acute coronary syndrome and death comparing patients with and without proton pump inhibitor treatment. To provide a more complete picture of the risks and benefits of treatment the investigators will also measure the relative rate of stomach bleeds in the same groups of patients. In addition, whether the inhibitory effect of proton pump inhibitors on the protective effect of clopidogrel is due to their inhibition of drug metabolising enzymes will be explored by assessing the effects of other drugs that inhibit the same enzymes.

Conditions

Coronary Heart Disease; Acute Coronary Syndrome; Drug Interactions; Clopidogrel; Proton Pump Inhibitors; Gastrointestinal Hemorrhage

Keywords

Coronary Heart Disease; Acute Coronary Syndrome; Drug interactions; Clopidogrel; Proton Pump Inhibitors; Gastrointestinal Hemorrhage

Outcome Measures

Primary Outcomes (1)

• Time to composite end point of all cause mortality OR incident myocardial infarction (MI)

  up to 12 years

Secondary Outcomes (2)

• Time to incident gastrointestinal (GI) bleed.

  up to 12 years

• Time to incident myocardial infarction

  up to 12 years

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

All patients registered in the GPRD from 1998 to date and receiving clopidogrel in combination with aspirin and with at least 12 months up to standard observation before the first prescription for clopidogrel will be eligible for inclusion. Data will be restricted to 1998 onwards as this is the year clopidogrel was licensed in the UK.

You may not qualify if:

• Data will be restricted to 1998 onwards as this is the year clopidogrel was licensed in the UK.

Sponsors & Collaborators

• London School of Hygiene and Tropical Medicine: lead
• University College, London: collaborator

Study Sites (1)

London School of Hygiene & Tropical Medicine

London, WC1E 7HT, United Kingdom

Location

Related Publications (6)

• Gilard M, Arnaud B, Le Gal G, Abgrall JF, Boschat J. Influence of omeprazol on the antiplatelet action of clopidogrel associated to aspirin. J Thromb Haemost. 2006 Nov;4(11):2508-9. doi: 10.1111/j.1538-7836.2006.02162.x. Epub 2006 Aug 8. No abstract available.

  PMID: 16898956 BACKGROUND

• Gilard M, Arnaud B, Cornily JC, Le Gal G, Lacut K, Le Calvez G, Mansourati J, Mottier D, Abgrall JF, Boschat J. Influence of omeprazole on the antiplatelet action of clopidogrel associated with aspirin: the randomized, double-blind OCLA (Omeprazole CLopidogrel Aspirin) study. J Am Coll Cardiol. 2008 Jan 22;51(3):256-60. doi: 10.1016/j.jacc.2007.06.064.

  PMID: 18206732 BACKGROUND

• Ho PM, Peterson ED, Wang L, Magid DJ, Fihn SD, Larsen GC, Jesse RA, Rumsfeld JS. Incidence of death and acute myocardial infarction associated with stopping clopidogrel after acute coronary syndrome. JAMA. 2008 Feb 6;299(5):532-9. doi: 10.1001/jama.299.5.532.

  PMID: 18252883 BACKGROUND

• Juurlink DN, Gomes T, Ko DT, Szmitko PE, Austin PC, Tu JV, Henry DA, Kopp A, Mamdani MM. A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. CMAJ. 2009 Mar 31;180(7):713-8. doi: 10.1503/cmaj.082001. Epub 2009 Jan 28.

  PMID: 19176635 BACKGROUND

• Sibbing D, Morath T, Stegherr J, Braun S, Vogt W, Hadamitzky M, Schomig A, Kastrati A, von Beckerath N. Impact of proton pump inhibitors on the antiplatelet effects of clopidogrel. Thromb Haemost. 2009 Apr;101(4):714-9.

  PMID: 19350116 BACKGROUND

• Douglas IJ, Evans SJ, Hingorani AD, Grosso AM, Timmis A, Hemingway H, Smeeth L. Clopidogrel and interaction with proton pump inhibitors: comparison between cohort and within person study designs. BMJ. 2012 Jul 10;345:e4388. doi: 10.1136/bmj.e4388.

  PMID: 22782731 DERIVED

Related Links

• London School of Hygiene \& Tropical Medicine
• General Practice Research Database
• CALIBER

MeSH Terms

Conditions

Coronary Disease; Acute Coronary Syndrome; Gastrointestinal Hemorrhage

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Gastrointestinal Diseases; Digestive System Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Ian J Douglas, PhD, MSc

  London School of Hygiene and Tropical Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Lecturer

Study Record Dates

• First Submitted: October 18, 2010
• First Posted: November 1, 2010
• Study Start: December 1, 2010
• Primary Completion: May 1, 2012
• Study Completion: May 1, 2012
• Last Updated: May 4, 2015

Record last verified: 2015-05

Locations

GB (1)