Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition. (Platform)

A Clinical Trial Comparing Treatment With Cangrelor (in Combination With Usual Care) to Usual Care, in Subjects Who Require Percutaneous Coronary Intervention (PCI).

The primary objective of this study is to demonstrate that the efficacy of cangrelor (combined with usual care) is superior to that of usual care, in subjects requiring percutaneous coronary intervention (PCI) as measured by a composite of all-cause mortality, myocardial infarction (MI), and ischemia-driven revascularization (IDR).

Study Overview

• Status: Terminated
• Conditions: Atherosclerosis; Acute Coronary Syndrome (ACS)
• Intervention / Treatment: Drug: Placebo bolus & placebo infusion; Drug: Placebo capsules - end of infusion; Drug: Cangrelor; Drug: clopidogrel; Drug: Placebo capsules - end of PCI

• Study Type: Interventional
• Enrollment (Actual): 5364
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • North Dakota
    • Fargo, North Dakota, United States, 58104
      • Innovis Health

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:

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.

Exclusion Criteria:

1. Not a candidate for PCI
2. ST-segment elevation myocardial infarction (STEMI) within 48 hours of randomization
3. Increased bleeding risk: ischemic stroke within the last year or any previous hemorrhagic stroke, intra-cranial tumor, cerebral arteriovenous malformation, or intracranial aneurysm; recent (<1 month) trauma or major surgery [including coronary artery bypass graft (CABG) surgery]; currently receiving warfarin, active bleeding
4. 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) at screening
5. Severe hypertension not adequately controlled by antihypertensive therapy at the time of randomization
6. Receipt of fibrinolytic therapy in the 12 hours preceding randomization
7. Receipt of any thienopyridine (clopidogrel or ticlopidine) in the 7 days preceding randomization
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]

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cangrelor; 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) + placebo capsules (to match) at end of PCI + active clopidogrel (600mg) immediately post infusion	Drug: Cangrelor; cangrelor bolus (30 mcg/kg) & cangrelor 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: clopidogrel; clopidogrel capsules (600 mg) at end of PCI; Other Names: Plavix; Drug: Placebo capsules - end of PCI; Placebo capsules given at the end of PCI to mimic 600mg clopidogrel dosing
Active Comparator: Clopidogrel; placebo bolus & infusion (to match) + clopidogrel capsules (600 mg) at end of PCI + placebo capsules (to match) immediately post infusion	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; Drug: clopidogrel; clopidogrel capsules (600 mg) at end of PCI; Other Names: Plavix

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)	mITT population; (composite incidence)	randomization through 48 hours post randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of All-cause Mortality or MI	mITT population	randomization through 48 hours post randomization
Incidence of All-cause Mortality	mITT population	randomization through 48 hours post randomization
Incidence of MI	mITT population	randomization through 48 hours post randomization
Incidence of IDR	mITT population	randomization through 48 hours post randomization
Incidence of Stent Thrombosis	mITT population	randomization through 48 hours post randomization
Incidence of Stroke	mITT	randomization through 48 hours post randomization
Incidence of All-cause Mortality	mITT population	randomization through 1 year post randomization
Incidence of Procedure Events [Abrupt Closure, Threatened Abrupt Closure, Need for Urgent Coronary Artery Bypass Graft (CABG) Surgery, Unsuccessful Procedure, New Thrombus or Suspected Thrombus, and/or Acute Stent Thrombosis]	mITT population A patient could have multiple procedural events.	During index PCI
Incidence of GUSTO Severe / Life-threatening	Major bleeding (non-CABG-related) - Safety population	randomization through 48 hours post randomization
Incidence of Thrombolysis in Myocardial Infarction (TIMI) Major	Major bleeding (non-CABG-related) - Safety population	randomization through 48 hours post randomization
Incidence of ACUITY Major Bleeding	Major bleeding (non-CABG-related) - Safety population	randomization through 48 hours post randomization
Incidence of ACUITY Major Bleeding Without Hematoma >/= 5 cm	Major bleeding (non-CABG-related) - Safety population excludes ACUITY major bleeding for which the only qualifying event was hematoma >/= 5 cm.	randomization through 48 hours post randomization
Incidence of All-cause Mortality, MI, or IDR	mITT population	randomization through 30 days post randomization
Incidence of All-cause Mortality or MI	mITT population	randomization through 30 days post randomization
Incidence of All-cause Mortality	mITT population	randomization through 30 days post randomization
Incidence of MI	mITT population	randomization through 30 days post randomization
Incidence of IDR	mITT population	randomization through 30 days post randomization
Incidence of Stent Thrombosis	mITT population	randomization through 30 days post randomization
Incidence of Stroke	mITT population	randomization through 30 days post randomization

Collaborators and Investigators

• Sponsor: The Medicines Company
• Investigators: Principal Investigator: Robert A. Harrington, MD, Duke University

Publications and helpful links

General Publications

• 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.
• Bhatt DL, Lincoff AM, Gibson CM, Stone GW, McNulty S, Montalescot G, Kleiman NS, Goodman SG, White HD, Mahaffey KW, Pollack CV Jr, Manoukian SV, Widimsky P, Chew DP, Cura F, Manukov I, Tousek F, Jafar MZ, Arneja J, Skerjanec S, Harrington RA; CHAMPION PLATFORM Investigators. Intravenous platelet blockade with cangrelor during PCI. N Engl J Med. 2009 Dec 10;361(24):2330-41. doi: 10.1056/NEJMoa0908629.
• 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: September 1, 2006
• Primary Completion (Actual): May 1, 2009
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: October 4, 2006
• First Submitted That Met QC Criteria: October 5, 2006
• First Posted (Estimate): October 6, 2006

Study Record Updates

• Last Update Posted (Estimate): May 5, 2014
• Last Update Submitted That Met QC Criteria: April 18, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: ACS; Percutaneous Coronary Intervention (PCI)
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; 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-05-03