A Clinical Trial to Demonstrate the Efficacy of Cangrelor

NCT00305162 | Terminated Phase 3 Results DMC

• 1 other identifier: TMC-CAN-05-02
• Study Type: interventional
• Target: 8,882
• Locations: 1 country
• Sites: 1

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.

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)

Outcome Measures

Primary Outcomes (1)

• Incidence of All-cause Mortality, Myocardial Infarction (MI), and Ischemia-driven Revascularization (IDR)

  (composite incidence)

  randomization through 48 hours after randomization

Secondary Outcomes (16)

• Incidence of All-cause Mortality and MI

  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

  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

  during index PCI

Study Arms (2)

Cangrelor

EXPERIMENTAL

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); Drug: clopidogrel (oral P2Y12 inhibitor); Drug: Placebo capsules - as soon as possible after randomization

Clopidogrel

ACTIVE COMPARATOR

clopidogrel capsules (600 mg) + placebo bolus \& infusion (to match) + placebo capsules (to match) post infusion

Drug: clopidogrel (oral P2Y12 inhibitor); Drug: Placebo bolus & placebo infusion; Drug: Placebo capsules - end of infusion

Interventions

Cangrelor (P2Y12 inhibitor) DRUG

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).

Cangrelor

clopidogrel (oral P2Y12 inhibitor) DRUG

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.

Also known as: Plavix

Cangrelor; Clopidogrel

Placebo bolus & placebo infusion DRUG

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)

Clopidogrel

Placebo capsules - end of infusion DRUG

Placebo capsules given at the end of infusion to mimic 600mg clopidogrel dosing

Clopidogrel

Placebo capsules - as soon as possible after randomization DRUG

Placebo capsules given as soon as possible after randomization to mimic 600mg clopidogrel dosing

Cangrelor

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Subjects will be excluded from the study if they present with any of the following:
• Not a candidate for PCI
• 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
• 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
• Severe hypertension not adequately controlled by antihypertensive therapy at the time of randomization
• Receipt of fibrinolytic therapy in the 12 hours preceding randomization
• Receipt of clopidogrel dose exceeding maintenance dose (ie, \>75 mg) at any time in the 5 days preceding randomization
• Inability to swallow study capsules
• Glycoprotein IIb/IIIa (GPI) Inhibitor usage within the previous 12 hours \[applicable to unstable angina (UA) and non-ST-elevation myocardial infarction (NSTEMI) patients\]

Sponsors & Collaborators

• The Medicines Company: lead

Study Sites (1)

Pennsylvania Hospital

Philadelphia, Pennsylvania, 19107-6192, United States

Location

Related Publications (8)

• 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.

  PMID: 19915221 RESULT

• Gutierrez JA, 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; CHAMPION Investigators. Efficacy and safety of cangrelor in patients with peripheral artery disease undergoing percutaneous coronary intervention - Insights from the CHAMPION program. Am Heart J Plus. 2021 Aug 25;9:100043. doi: 10.1016/j.ahjo.2021.100043. eCollection 2021 Sep.

  PMID: 38551015 DERIVED

• 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.

  PMID: 35196863 DERIVED

• 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.

  PMID: 29632238 DERIVED

• 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.

  PMID: 28988157 DERIVED

• 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.

  PMID: 28382371 DERIVED

• 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.

  PMID: 27902833 DERIVED

• 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.

  PMID: 22305835 DERIVED

MeSH Terms

Conditions

Myocardial Infarction; Acute Coronary Syndrome; Non-ST Elevated Myocardial Infarction; ST Elevation Myocardial Infarction

Interventions

cangrelor; Clopidogrel

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

Discontinued per prespecified stopping rules after the 70% interim analyses was conducted indicating the trial was not likely to meet the goal of demonstrating superiority to clopidogrel administered as usual care. No safety issues were identified.

Results Point of Contact

• Title: Meredith Todd
• Organization: The Medicines Company

meredith.todd@themedco.com

+19732906088

Study Officials

• Deepak L. Bhatt, MD

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

• Robert A. Harrington, MD

  Duke University Medical Center and Duke Clinical Research Institute

  PRINCIPAL INVESTIGATOR

• Simona Skerjanec, PharmD

  The Medicines Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2006
• First Posted: March 21, 2006
• Study Start: April 1, 2006
• Primary Completion: May 1, 2009
• Study Completion: June 1, 2010
• Last Updated: May 8, 2014
• Results First Posted: April 23, 2014

Record last verified: 2014-04

Locations

US (1)