PPI and Clopidogrel Response

NCT01170533 | Completed Phase 1 Results DMC

• 1 other identifier: UFJ 2009-2
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Clopidogrel, in combination with aspirin, is currently the recommended treatment for secondary prevention of ischemic events in high-risk patients and for prevention of coronary artery stent thrombosis. Patients receiving aspirin and clopidogrel are frequently treated with proton pump inhibitors, such as omeprazole or pantoprazole, in order to prevent the risk of gastrointestinal bleeding, accorded to guidelines. An interaction between proton pump inhibitors and clopidogrel has been suggested, which may lead to a decrease of clopidogrel effects. It remains unclear whether this interaction between PPIs and clopidogrel might be a class effect or if this may be affected by timing regimen. The objectives of this two-phase investigation are:

1. 1.to compare clopidogrel platelet inhibitory effects when taken at the same time versus separated at least 8 hours from omeprazole administration.
2. 2.to compare clopidogrel-induced inhibitory effects when taken at the same time versus staggered at least 8 hours from pantoprazole administration.

Conditions

Drug Interaction

Keywords

proton pump inhibitor; clopidogrel; platelet function

Outcome Measures

Primary Outcomes (1)

• Platelet Function as Assessed by the P2Y12 Reactivity Index

  P2Y12 reactivity index which will be assessed by flow cytometry determination of vasodilator-stimulated phosphoprotein (VASP).

  1 week

Study Arms (2)

Omeprazole

ACTIVE COMPARATOR

prospective, open-label, two-sequence, three-period, randomized crossover study

Drug: omeprazole and pantoprazole

Pantoprazole

ACTIVE COMPARATOR

prospective, open-label, two-sequence, three-period, randomized crossover study

Drug: omeprazole and pantoprazole

Interventions

omeprazole and pantoprazole DRUG

The clopidogrel dose will be a 600mg loading dose followed by a 75mg daily maintenance dose, starting the next day for 7 days. Omeprazole will be used at a daily dose of 40mg and pantoprazole at 80mg.

Omeprazole; Pantoprazole

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy volunteers aged between 18 and 75 years

You may not qualify if:

• Known allergies to clopidogrel or omeprazole.
• Blood dyscrasia or bleeding diathesis.
• Recent antiplatelet treatment (\< 30 days) with a glycoprotein IIb/IIIa antagonist, thienopyridine (ticlopidine, clopidogrel), cilostazol or dipyridamole.
• Treatment with other medications that may interfere with the CYP system (ketoconazole, itraconazole, diltiazem, erythromycin, clarithromycin, fluvoxamine, fluoxetine, nefazodone, or sertraline).
• Platelet count \<100x106/microL.
• Diabetes mellitus
• History of coronary artery disease, gastrointestinal bleed, gastroesophageal reflux disease (GERD), cerebrovascular event or any active malignancy.
• Active bleeding or hemodynamic instability.
• Serum creatinine \>2mg/dL.
• Baseline ALT \>2.5 times the upper limit of normal.
• Pregnant females.
• Patients taking omeprazole or any H2 antagonist or proton pump inhibitors

Sponsors & Collaborators

• University of Florida: lead
• Bristol-Myers Squibb: collaborator
• Sanofi: collaborator

Study Sites (1)

University of Florida

Jacksonville, Florida, 32209, United States

Location

Related Publications (2)

• Ferreiro JL, Ueno M, Capodanno D, Desai B, Dharmashankar K, Darlington A, Charlton RK, Bass TA, Angiolillo DJ. Pharmacodynamic effects of concomitant versus staggered clopidogrel and omeprazole intake: results of a prospective randomized crossover study. Circ Cardiovasc Interv. 2010 Oct;3(5):436-41. doi: 10.1161/CIRCINTERVENTIONS.110.957829. Epub 2010 Sep 21.

  PMID: 20858862 RESULT

• Ferreiro JL, Ueno M, Tomasello SD, Capodanno D, Desai B, Dharmashankar K, Seecheran N, Kodali MK, Darlington A, Pham JP, Tello-Montoliu A, Charlton RK, Bass TA, Angiolillo DJ. Pharmacodynamic evaluation of pantoprazole therapy on clopidogrel effects: results of a prospective, randomized, crossover study. Circ Cardiovasc Interv. 2011 Jun;4(3):273-9. doi: 10.1161/CIRCINTERVENTIONS.110.960997. Epub 2011 Apr 26.

  PMID: 21521834 RESULT

MeSH Terms

Interventions

Omeprazole; Pantoprazole

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Dominick J. Angiolillo, MD, PhD
• Organization: University of Florida-Jacksonville

dominick.angiolillo@jax.ufl.edu

904-244-3933

Study Officials

• Dominick J Angiolillo, MD, PhD

  University of Florida

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2010
• First Posted: July 27, 2010
• Study Start: March 1, 2009
• Primary Completion: August 1, 2010
• Study Completion: August 1, 2010
• Last Updated: March 6, 2012
• Results First Posted: March 6, 2012

Record last verified: 2012-03

Locations

US (1)