A Clinical Trial to Demonstrate the Efficacy of Cangrelor (PCI)

A Clinical Trial Comparing Cangrelor to Clopidogrel in Subjects Who Require Percutaneous Coronary Intervention (PCI).

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.

Study Overview

• Status: Terminated
• Conditions: Myocardial Infarction (MI); Acute Coronary Syndromes (ACS)
• Intervention / Treatment: Drug: Cangrelor (P2Y12 inhibitor); Drug: clopidogrel (oral P2Y12 inhibitor); Drug: Placebo capsules - as soon as possible after randomization; Drug: Placebo bolus & placebo infusion; Drug: Placebo capsules - end of infusion

• Study Type: Interventional
• Enrollment (Actual): 8882
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107-6192
      • Pennsylvania Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Cangrelor; placebo capsules (to match) + cangrelor bolus (30 mcg/kg) & infusion (4 mcg/kg/min) administered from randomization for at least 2 hours, or until the end of the PCI, whichever is longer with the option to extend up to 4 hours maximum (per investigator discretion) + active clopidogrel (600mg) post infusion	Drug: Cangrelor (P2Y12 inhibitor); IV bolus (30 mcg/kg) & infusion (4 mcg/kg/min) initiated prior to PCI, as soon as possible following randomization (after need for PCI is confirmed) but not more than 30 minutes prior to placement of arterial access. Infusion is to continue for at least 2 hours, or until the end of the PCI, whichever is longer with the option to extend up to 4 hours maximum (per investigator discretion).; Drug: clopidogrel (oral P2Y12 inhibitor); 600 mg active clopidogrel administered as soon as possible following randomization (after need for PCI confirmed), but not more than 30 minutes prior to the placement of the arterial access.; Other Names: Plavix; Drug: Placebo capsules - as soon as possible after randomization; Placebo capsules given as soon as possible after randomization to mimic 600mg clopidogrel dosing
ACTIVE_COMPARATOR: Clopidogrel; clopidogrel capsules (600 mg) + placebo bolus & infusion (to match) + placebo capsules (to match) post infusion	Drug: clopidogrel (oral P2Y12 inhibitor); 600 mg active clopidogrel administered as soon as possible following randomization (after need for PCI confirmed), but not more than 30 minutes prior to the placement of the arterial access.; Other Names: Plavix; Drug: Placebo bolus & placebo infusion; placebo bolus (30 mcg/kg) & placebo infusion (4 mcg/kg/min) administered from randomization for at least 2 hours, or until the end of the PCI, whichever is longer with the option to extend up to 4 hours maximum (per investigator discretion); Drug: Placebo capsules - end of infusion; Placebo capsules given at the end of infusion to mimic 600mg clopidogrel dosing

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of All-cause Mortality, Myocardial Infarction (MI), and Ischemia-driven Revascularization (IDR)	(composite incidence)	randomization through 48 hours after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of All-cause Mortality and MI	(composite incidence)	randomization through 48 hours after randomization
Individual Incidence of All-cause Mortality		randomization through 48 hours after randomization
Individual Incidence of IDR		randomization through 48 hours after randomization
Incidence of Stroke	Stroke is defined as a sudden, focal neurological defect resulting from a cerebrovascular cause that is not reversible within 24 hours and not due to a readily identifiable cause such as a tumor or trauma. All suspected strokes were reviewed and adjudicated by the Clinical Events Committee (CEC) who considered all clinically relevant information and imaging studies to classify all strokes as: primary hemorrhagic - stroke with focal collections of intracranial blood; ischemic cerebral infarction - stroke without focal collections of intracranial blood; infarction with hemorrhagic conversion - cerebral infarction with blood thought to represent hemorrhagic conversion and not primary bleeding; uncertain - no imaging or autopsy data are available.	randomization through 48 hours after randomization
Incidence of Abrupt Closure, Threatened Abrupt Closure, Need for Urgent Coronary Artery Bypass Graft (CABG) Surgery, or Unsuccessful Procedure During the Index PCI	(a patient could have multiple procedural events)	during index PCI
Incidence of All-cause Mortality, MI or IDR	(composite incidence)	randomization through 30 days after randomization
Incidence of All-cause Mortality or MI	(composite incidence)	randomization through 30 days after randomization
Incidence of All-cause Mortality		randomization through 30 days after randomization
Incidence of MI		randomization through 30 days after randomization
Incidence of IDR		randomization through 30 days after randomization
Incidence of Stroke		randomization through 30 days after randomization
Incidence of All Cause Mortality	(excluding STEMI)	randomization through 1 year after randomization
Incidence of GUSTO Severe / Life-threatening Bleeding	Major bleeding (non-CABG-related) - Safety population	randomization through 48 hours after randomization
Incidence of Thrombolysis in Myocardial Infarction (TIMI) Major Bleeding	Major bleeding (non-CABG-related) - Safety population	randomization through 48 hours after randomization
Incidence of ACUITY Major Bleeding	Major bleeding (non-CABG-related) - Safety population	randomization through 48 hours after randomization
Incidence of ACUITY Major Bleeding (Without Hematoma >/= 5 cm)	excludes ACUITY major bleeding for which the only qualifying event was hematoma >/= 5 cm	randomization through 48 hours after randomization

Collaborators and Investigators

• Sponsor: The Medicines Company
• Investigators: Principal Investigator: Robert A. Harrington, MD, Duke University Medical Center and Duke Clinical Research Institute

Publications and helpful links

General Publications

• 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.
• 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.
• 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. Erratum In: Circ Cardiovasc Interv. 2018 Sep;11(9):e000036. Angiolillo, Dominick [corrected to Angiolillo, Dominick J].
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: April 1, 2006
• Primary Completion (ACTUAL): May 1, 2009
• Study Completion (ACTUAL): June 1, 2010

Study Registration Dates

• First Submitted: March 17, 2006
• First Submitted That Met QC Criteria: March 20, 2006
• First Posted (ESTIMATE): March 21, 2006

Study Record Updates

• Last Update Posted (ESTIMATE): May 8, 2014
• Last Update Submitted That Met QC Criteria: April 22, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: Acute Coronary Syndrome (ACS); Percutaneous Coronary Intervention (PCI); ST-segment elevation myocardial infarction (STEMI); non-ST-segment elevation myocardial infarction (NSTEMI)
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Acute Coronary Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Clopidogrel; Cangrelor
• Other Study ID Numbers: TMC-CAN-05-02