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

This study has been terminated.
(Insufficient evidence of the clinical effectiveness of cangrelor)
Sponsor:
Information provided by (Responsible Party):
The Medicines Company
ClinicalTrials.gov Identifier:
NCT00305162
First received: March 17, 2006
Last updated: April 22, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Myocardial Infarction (MI)
Acute Coronary Syndromes (ACS)
Drug: Cangrelor (P2Y12 inhibitor)
Drug: clopidogrel (oral P2Y12 inhibitor)
Drug: Placebo bolus & placebo infusion
Drug: Placebo capsules - end of infusion
Drug: Placebo capsules - as soon as possible after randomization
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Clinical Trial Comparing Cangrelor to Clopidogrel in Subjects Who Require Percutaneous Coronary Intervention (PCI).

Resource links provided by NLM:


Further study details as provided by The Medicines Company:

Primary Outcome Measures:
  • Incidence of All-cause Mortality, Myocardial Infarction (MI), and Ischemia-driven Revascularization (IDR) [ Time Frame: randomization through 48 hours after randomization ] [ Designated as safety issue: No ]
    (composite incidence)


Secondary Outcome Measures:
  • Incidence of All-cause Mortality and MI [ Time Frame: randomization through 48 hours after randomization ] [ Designated as safety issue: No ]
    (composite incidence)

  • Individual Incidence of All-cause Mortality [ Time Frame: randomization through 48 hours after randomization ] [ Designated as safety issue: No ]
  • Individual Incidence of IDR [ Time Frame: randomization through 48 hours after randomization ] [ Designated as safety issue: No ]
  • Incidence of Stroke [ Time Frame: randomization through 48 hours after randomization ] [ Designated as safety issue: No ]

    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.

  • Incidence of Abrupt Closure, Threatened Abrupt Closure, Need for Urgent Coronary Artery Bypass Graft (CABG) Surgery, or Unsuccessful Procedure During the Index PCI [ Time Frame: during index PCI ] [ Designated as safety issue: No ]
    (a patient could have multiple procedural events)

  • Incidence of All-cause Mortality, MI or IDR [ Time Frame: randomization through 30 days after randomization ] [ Designated as safety issue: No ]
    (composite incidence)

  • Incidence of All-cause Mortality or MI [ Time Frame: randomization through 30 days after randomization ] [ Designated as safety issue: No ]
    (composite incidence)

  • Incidence of All-cause Mortality [ Time Frame: randomization through 30 days after randomization ] [ Designated as safety issue: No ]
  • Incidence of MI [ Time Frame: randomization through 30 days after randomization ] [ Designated as safety issue: No ]
  • Incidence of IDR [ Time Frame: randomization through 30 days after randomization ] [ Designated as safety issue: No ]
  • Incidence of Stroke [ Time Frame: randomization through 30 days after randomization ] [ Designated as safety issue: No ]
  • Incidence of All Cause Mortality [ Time Frame: randomization through 1 year after randomization ] [ Designated as safety issue: No ]
    (excluding STEMI)

  • Incidence of GUSTO Severe / Life-threatening Bleeding [ Time Frame: randomization through 48 hours after randomization ] [ Designated as safety issue: Yes ]
    Major bleeding (non-CABG-related) - Safety population

  • Incidence of Thrombolysis in Myocardial Infarction (TIMI) Major Bleeding [ Time Frame: randomization through 48 hours after randomization ] [ Designated as safety issue: Yes ]
    Major bleeding (non-CABG-related) - Safety population

  • Incidence of ACUITY Major Bleeding [ Time Frame: randomization through 48 hours after randomization ] [ Designated as safety issue: Yes ]
    Major bleeding (non-CABG-related) - Safety population

  • Incidence of ACUITY Major Bleeding (Without Hematoma >/= 5 cm) [ Time Frame: randomization through 48 hours after randomization ] [ Designated as safety issue: Yes ]
    excludes ACUITY major bleeding for which the only qualifying event was hematoma >/= 5 cm


Enrollment: 8882
Study Start Date: April 2006
Study Completion Date: June 2010
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00305162

Locations
United States, Pennsylvania
Pennsylvania Hospital
Philadelphia, Pennsylvania, United States, 19107-6192
Sponsors and Collaborators
The Medicines Company
Investigators
Principal Investigator: Deepak L. Bhatt, MD The Cleveland Clinic
Principal Investigator: Robert A. Harrington, MD Duke University Medical Center and Duke Clinical Research Institute
Study Director: Simona Skerjanec, PharmD The Medicines Company
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: The Medicines Company
ClinicalTrials.gov Identifier: NCT00305162     History of Changes
Other Study ID Numbers: TMC-CAN-05-02
Study First Received: March 17, 2006
Results First Received: April 22, 2013
Last Updated: April 22, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by The Medicines Company:
Acute Coronary Syndrome (ACS)
Percutaneous Coronary Intervention (PCI)
non-ST-segment elevation myocardial infarction (NSTEMI)
ST-segment elevation myocardial infarction (STEMI)

Additional relevant MeSH terms:
Infarction
Myocardial Infarction
Acute Coronary Syndrome
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Angina Pectoris
Chest Pain
Pain
Signs and Symptoms
Clopidogrel
Ticlopidine
Cangrelor
Platelet Aggregation Inhibitors
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Fibrinolytic Agents
Fibrin Modulating Agents

ClinicalTrials.gov processed this record on July 20, 2014