NCT00642811

Brief Summary

The purpose of this study is to see how Ticagrelor, a new oral reversible anti-platelet medication, affects platelets. Anti-platelet agents are medications that block the formation of blood clots by preventing the clumping of platelets. Blood clots prevent us from bleeding, but when they form inside the arteries their formation is linked to a risk of medical problems such as heart attack and stroke. This study investigated the effect of Ticagrelor on inhibition of platelet aggregation compared with clopidogrel in patients previously identified as non-responsive to clopidogrel.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
98

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started May 2008

Shorter than P25 for phase_2

Geographic Reach
4 countries

10 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 19, 2008

Completed
6 days until next milestone

First Posted

Study publicly available on registry

March 25, 2008

Completed
1 month until next milestone

Study Start

First participant enrolled

May 1, 2008

Completed
10 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2009

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2009

Completed
2.6 years until next milestone

Results Posted

Study results publicly available

October 4, 2011

Completed
Last Updated

October 4, 2011

Status Verified

August 1, 2011

Enrollment Period

10 months

First QC Date

March 19, 2008

Results QC Date

January 27, 2011

Last Update Submit

August 30, 2011

Conditions

Stable Coronary Artery Disease

Keywords

coronary artery disease (CAD)heart attackstable angina

Outcome Measures

Primary Outcomes (2)

  • Proportion of Clopidogrel Non-responders Who Responded to Clopidogrel or Ticagrelor. - Comparing Ticag. (Day 28 of Clop. to Ticag., and Day 14 of Ticag. to Clop.) Versus Clop. (Day 14 of Clop. to Ticag., and Day 28 of Ticag. to Clop.)

    The primary definition of response to treatment is IPA \>10% post treatment. The response is reported as percentage of participants of each treatment. Please refer to the protocol section for details about the interventions administered. IPA(%)=(PAb-PAt)/PAb\*100. PA (platelet aggregation) is measured by LTA (Light Transmittance Aggregometry). PAb is the response at baseline (last measurement before study drug) and PAt is a response at post-treatment. IPA=0% means no PA inhibition and 100% means 100% PA inhibition.

    Day 14 and Day 28, 4 Hrs Post Dose.

  • Proportion of Clopidogrel Non-responders Who Responded to Clopidogrel or Ticagrelor. - Comparing Ticag. (Day 28 of Clop. to Ticag., and Day 14 of Ticag. to Clop.) Versus Clop. (Day 14 of Clop. to Ticag., and Day 28 of Ticag. to Clop.

    The secondary definition of response to treatment is IPA \>50% post treatment. The response is reported as percentage of participants of each treatment. Please refer to the protocol section for details about the interventions administered. IPA(%)=(PAb-PAt)/PAb\*100. PA (platelet aggregation) is measured by LTA (Light Transmittance Aggregometry). PAb is the response at baseline (last measurement before study drug) and PAt is a response at post-treatment. IPA=0% means no PA inhibition and 100% means 100% PA inhibition.

    Day 14, and day 28, 4 hours post dose

Secondary Outcomes (4)

  • Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Ticagrelor to Ticagrelor Versus Ticagrelor to Clopidogrel on Day 15

    Day 15, 4 hrs post switching

  • Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Ticagrelor to Ticagrelor Versus Ticagrelor to Clopidogrel on Day 28

    4 hrs post first dose on day 28

  • Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Clopidogrel to Clopidogrel Versus Clopidogrel to Ticagrelor on Day 15

    Day 15, 4 hrs post switching

  • Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Clopidogrel to Clopidogrel Versus Clopidogrel to Ticagrelor on Day 28

    4 hrs post first dose on day 28

Study Arms (2)

1

EXPERIMENTAL

Aspirin + Ticagrelor

Drug: TicagrelorDrug: Aspirin

2

ACTIVE COMPARATOR

Aspirin + Clopidogrel

Drug: ClopidogrelDrug: Aspirin

Interventions

TicagrelorDRUG

Tablets, Oral, 90 mg; 180 mg loading dose followed by 90 mg twice daily for 2 weeks

1
ClopidogrelDRUG

(over encapsulated) capsule, Oral, 75 mg; 600 mg loading dose followed by 75 mg once daily for 2 weeks

Also known as: Plavix
2
AspirinDRUG

Tablets, Oral, 75 mg to 100 mg once daily. Aspirin obtained locally by the investigator, according to local practice. The dose remained constant throughout the study

12

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients with documented stable Coronary Artery Disease (CAD) (stable angina, previous MI history, previous history of revascularization)
  • Females of child bearing potential must have a negative pregnancy test prior to receiving study drug and be willing to use a hormonal contraceptive in addition to double barrier contraception

You may not qualify if:

  • History of Acute Coronary Syndromes within 12 months of screening or need for revascularization (angioplasty or coronary artery bypass graft (CABG))
  • Any acute or chronic unstable condition in the past 30 days
  • Have increased bleeding risk, eg, recent gastrointestinal bleed, uncontrolled high blood pressure, low platelet count, recent major trauma
  • History of intolerance or allergy to aspirin or clopidogrel

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (10)

Research Site

Jonesboro, Arkansas, United States

Location

Research Site

Ormond Beach, Florida, United States

Location

Research Site

Baltimore, Maryland, United States

Location

Research Site

Cincinnati, Ohio, United States

Location

Research Site

Hamilton, Ontario, Canada

Location

Research Site

Lachine, Canada

Location

Research Site

Aalborg, Denmark

Location

Research Site

Aarhus, Denmark

Location

Research Site

Esbjerg, Denmark

Location

Research Site

Sheffield, United Kingdom

Location

Related Publications (4)

  • Jeong YH, Bliden KP, Antonino MJ, Park KS, Tantry US, Gurbel PA. Usefulness of the VerifyNow P2Y12 assay to evaluate the antiplatelet effects of ticagrelor and clopidogrel therapies. Am Heart J. 2012 Jul;164(1):35-42. doi: 10.1016/j.ahj.2012.03.022. Epub 2012 Jun 13.

    PMID: 22795280DERIVED

  • Jeong YH, Bliden KP, Tantry US, Gurbel PA. High on-treatment platelet reactivity assessed by various platelet function tests: is the consensus-defined cut-off of VASP-P platelet reactivity index too low? J Thromb Haemost. 2012 Mar;10(3):487-9. doi: 10.1111/j.1538-7836.2011.04604.x. No abstract available.

    PMID: 22212857DERIVED

  • Tantry US, Bliden KP, Wei C, Storey RF, Armstrong M, Butler K, Gurbel PA. First analysis of the relation between CYP2C19 genotype and pharmacodynamics in patients treated with ticagrelor versus clopidogrel: the ONSET/OFFSET and RESPOND genotype studies. Circ Cardiovasc Genet. 2010 Dec;3(6):556-66. doi: 10.1161/CIRCGENETICS.110.958561. Epub 2010 Nov 15.

    PMID: 21079055DERIVED

  • Gurbel PA, Bliden KP, Butler K, Antonino MJ, Wei C, Teng R, Rasmussen L, Storey RF, Nielsen T, Eikelboom JW, Sabe-Affaki G, Husted S, Kereiakes DJ, Henderson D, Patel DV, Tantry US. Response to ticagrelor in clopidogrel nonresponders and responders and effect of switching therapies: the RESPOND study. Circulation. 2010 Mar 16;121(10):1188-99. doi: 10.1161/CIRCULATIONAHA.109.919456. Epub 2010 Mar 1.

    PMID: 20194878DERIVED

MeSH Terms

Conditions

Coronary Artery DiseaseMyocardial InfarctionAngina, Stable

Interventions

TicagrelorClopidogrelAspirin

Condition Hierarchy (Ancestors)

Coronary DiseaseMyocardial IschemiaHeart DiseasesCardiovascular DiseasesArteriosclerosisArterial Occlusive DiseasesVascular DiseasesInfarctionIschemiaPathologic ProcessesPathological Conditions, Signs and SymptomsNecrosisAngina PectorisChest PainPainNeurologic ManifestationsSigns and Symptoms

Intervention Hierarchy (Ancestors)

AdenosinePurine NucleosidesPurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsNucleosidesNucleic Acids, Nucleotides, and NucleosidesRibonucleosidesTiclopidineThienopyridinesThiophenesSulfur CompoundsOrganic ChemicalsPyridinesHeterocyclic Compounds, 1-RingSalicylatesHydroxybenzoatesPhenolsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbons

Results Point of Contact

Title
Gerard Lynch
Organization
AstraZeneca
aztrial_results_posting@astrazeneca.com

Study Officials

  • Jay Horrow, MD

    AstraZeneca

    STUDY DIRECTOR

  • Paul Gurbel, md

    Platelet & Thrombosis Research, LLC

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 19, 2008

First Posted

March 25, 2008

Study Start

May 1, 2008

Primary Completion

March 1, 2009

Study Completion

March 1, 2009

Last Updated

October 4, 2011

Results First Posted

October 4, 2011

Record last verified: 2011-08

Locations

US(4)CA(2)DK(3)GB(1)