Clinical trial NCT00305162: A Clinical Trial to Demonstrate the Efficacy of Cangrelor
Official title: A Clinical Trial Comparing Cangrelor to Clopidogrel in Subjects Who Require Percutaneous Coronary Intervention (PCI).
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Myocardial Infarction (MI)
Acute Coronary Syndromes (ACS)
Keywords: Acute Coronary Syndrome (ACS)
Percutaneous Coronary Intervention (PCI)
non-ST-segment elevation myocardial infarction (NSTEMI)
ST-segment elevation myocardial infarction (STEMI)
Lead sponsor: The Medicines Company
Sponsor class: INDUSTRY
First posted: 2006-03-21
Enrollment: 8882
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to demonstrate that the efficacy of cangrelor is superior, or at least non-inferior, to that of clopidogrel in subjects requiring PCI.


Eligibility criteria: INCLUSION CRITERIA

To be included in this study, subjects must meet the following criteria:

* Angiography demonstrating atherosclerosis amenable to treatment by percutaneous coronary intervention (PCI) with or without stent implantation and diagnosis of Acute Coronary Syndrome (ACS) by elevated cardiac markers or ischemic chest discomfort w/electrocardiogram changes + age \> 65 or diabetes or ST-elevation MI.

EXCLUSION CRITERIA

Subjects will be excluded from the study if they present with any of the following:

1. Not a candidate for PCI
2. Increased bleeding risk: ischemic stroke within the last year or any previous hemorrhagic stroke, tumor, cerebral arteriovenous malformation, or intracranial aneurysm; recent (\<1 month) trauma or major surgery (including by-pass surgery); currently receiving warfarin, active bleeding
3. Impaired hemostasis: known International Normalized Ratio (INR) \>1.5 at screening; past or present bleeding disorder (including congenital bleeding disorders such as von Willebrand's disease or hemophilia, acquired bleeding disorders, and unexplained clinically significant bleeding disorders), thrombocytopenia (platelet count \<100,000/µL), or history of thrombocytopenia or neutropenia associated with clopidogrel
4. Severe hypertension not adequately controlled by antihypertensive therapy at the time of randomization
5. Receipt of fibrinolytic therapy in the 12 hours preceding randomization
6. Receipt of clopidogrel dose exceeding maintenance dose (ie, \>75 mg) at any time in the 5 days preceding randomization
7. Inability to swallow study capsules
8. Glycoprotein IIb/IIIa (GPI) Inhibitor usage within the previous 12 hours \[applicable to unstable angina (UA) and non-ST-elevation myocardial infarction (NSTEMI) patients\]

Subjects excluded for any of the above reasons may be re-screened for participation at any time if the exclusion characteristic has changed.

Primary outcomes:
measure: Incidence of All-cause Mortality, Myocardial Infarction (MI), and Ischemia-driven Revascularization (IDR)
timeFrame: randomization through 48 hours after randomization
Secondary outcomes:
measure: Incidence of All-cause Mortality and MI
timeFrame: randomization through 48 hours after randomization
measure: Individual Incidence of All-cause Mortality
timeFrame: randomization through 48 hours after randomization
measure: Individual Incidence of IDR
timeFrame: randomization through 48 hours after randomization
measure: Incidence of Stroke
timeFrame: randomization through 48 hours after randomization
measure: Incidence of Abrupt Closure, Threatened Abrupt Closure, Need for Urgent Coronary Artery Bypass Graft (CABG) Surgery, or Unsuccessful Procedure During the Index PCI
timeFrame: during index PCI
measure: Incidence of All-cause Mortality, MI or IDR
timeFrame: randomization through 30 days after randomization
measure: Incidence of All-cause Mortality or MI
timeFrame: randomization through 30 days after randomization
measure: Incidence of All-cause Mortality
timeFrame: randomization through 30 days after randomization
measure: Incidence of MI
timeFrame: randomization through 30 days after randomization
measure: Incidence of IDR
timeFrame: randomization through 30 days after randomization
measure: Incidence of Stroke
timeFrame: randomization through 30 days after randomization
measure: Incidence of All Cause Mortality
timeFrame: randomization through 1 year after randomization
measure: Incidence of GUSTO Severe / Life-threatening Bleeding
timeFrame: randomization through 48 hours after randomization
measure: Incidence of Thrombolysis in Myocardial Infarction (TIMI) Major Bleeding
timeFrame: randomization through 48 hours after randomization
measure: Incidence of ACUITY Major Bleeding
timeFrame: randomization through 48 hours after randomization
measure: Incidence of ACUITY Major Bleeding (Without Hematoma >/= 5 cm)
timeFrame: randomization through 48 hours after randomization
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Pennsylvania Hospital
state: Pennsylvania
Study officials:
affiliation: The Cleveland Clinic
name: Deepak L. Bhatt, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University Medical Center and Duke Clinical Research Institute
name: Robert A. Harrington, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Medicines Company
name: Simona Skerjanec, PharmD
role: STUDY_DIRECTOR
References:
citation: Harrington RA, Stone GW, McNulty S, White HD, Lincoff AM, Gibson CM, Pollack CV Jr, Montalescot G, Mahaffey KW, Kleiman NS, Goodman SG, Amine M, Angiolillo DJ, Becker RC, Chew DP, French WJ, Leisch F, Parikh KH, Skerjanec S, Bhatt DL. Platelet inhibition with cangrelor in patients undergoing PCI. N Engl J Med. 2009 Dec 10;361(24):2318-29. doi: 10.1056/NEJMoa0908628.
citation: Peterson BE, Harrington RA, Stone GW, Steg PG, Gibson CM, Hamm CW, Price MJ, Lopes RD, Leonardi S, Prats J, Deliargyris EN, Mahaffey KW, White HD, Bhatt DL. Effect of Platelet Inhibition by Cangrelor Among Obese Patients Undergoing Coronary Stenting: Insights From CHAMPION. Circ Cardiovasc Interv. 2022 Mar;15(3):e011069. doi: 10.1161/CIRCINTERVENTIONS.121.011069. Epub 2022 Feb 24.
citation: Groves EM, Bhatt DL, Steg PG, Deliargyris EN, Stone GW, Gibson CM, Hamm CW, Mahaffey KW, White HD, Angiolillo DJ, Prats J, Harrington RA, Price MJ. Incidence, Predictors, and Outcomes of Acquired Thrombocytopenia After Percutaneous Coronary Intervention: A Pooled, Patient-Level Analysis of the CHAMPION Trials (Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition). Circ Cardiovasc Interv. 2018 Apr;11(4):e005635. doi: 10.1161/CIRCINTERVENTIONS.117.005635.
citation: Vaduganathan M, Harrington RA, Stone GW, Steg G, Gibson CM, Hamm CW, Price MJ, Lopes RD, Leonardi S, Deliargyris EN, Prats J, Mahaffey KW, White HD, Bhatt DL. Short- and long-term mortality following bleeding events in patients undergoing percutaneous coronary intervention: insights from four validated bleeding scales in the CHAMPION trials. EuroIntervention. 2018 Feb 2;13(15):e1841-e1849. doi: 10.4244/EIJ-D-17-00723.
citation: Parker WA, Bhatt DL, Prats J, Day JRS, Steg PG, Stone GW, Hamm CW, Mahaffey KW, Price MJ, Gibson CM, White HD, Storey RF; CHAMPION PHOENIX Investigators. Characteristics of dyspnoea and associated clinical outcomes in the CHAMPION PHOENIX study. Thromb Haemost. 2017 Jun 2;117(6):1093-1100. doi: 10.1160/TH16-12-0958. Epub 2017 Apr 6.
citation: Vaduganathan M, Harrington RA, Stone GW, Deliargyris EN, Steg PG, Gibson CM, Hamm CW, Price MJ, Menozzi A, Prats J, Elkin S, Mahaffey KW, White HD, Bhatt DL. Evaluation of Ischemic and Bleeding Risks Associated With 2 Parenteral Antiplatelet Strategies Comparing Cangrelor With Glycoprotein IIb/IIIa Inhibitors: An Exploratory Analysis From the CHAMPION Trials. JAMA Cardiol. 2017 Feb 1;2(2):127-135. doi: 10.1001/jamacardio.2016.4556.
citation: White HD, Chew DP, Dauerman HL, Mahaffey KW, Gibson CM, Stone GW, Gruberg L, Harrington RA, Bhatt DL. Reduced immediate ischemic events with cangrelor in PCI: a pooled analysis of the CHAMPION trials using the universal definition of myocardial infarction. Am Heart J. 2012 Feb;163(2):182-90.e4. doi: 10.1016/j.ahj.2011.11.001.