E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subjects who present with an acute coronary syndrome. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10051592 |
E.1.2 | Term | Acute coronary syndrome |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10051592 |
E.1.2 | Term | Acute coronary syndrome |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10006894 |
E.1.2 | Term | CABG |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Stage I The primary objective of the open-label Stage I portion of this study is to identify a dose of cangrelor (between 0.5 μg/kg/min and 2.0 μg/kg/min) that achieves and maintains > 60% platelet inhibition in at least 80% of samples as determined by the Accumetrics VerifyNow™ P2Y12 assay in patients who have discontinued thienopyridine therapy.
Stage II The primary efficacy objective of Stage II in this study is to demonstrate that a cangrelor infusion (as determined in Stage I) will maintain levels of residual platelet reactivity (PRU < 240) as measured by Accumetrics VerifyNow™ P2Y12 assay). This level is the equivalent to those levels expected to be maintained if a thienopyridine (clopidogrel, ticlopidine, or prasugrel) had not been discontinued.
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E.2.2 | Secondary objectives of the trial |
The main safety objective is to demonstrate that patients receiving cangrelor infusion before coronary artery bypass grafting have an acceptable safety profile and can undergo surgery without excessive bleeding peri-operatively. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Provide written informed consent before initiation of any study related procedures. 2. Be at least 18 years of age. 3. Anticipate non-emergent coronary artery bypass graft (CABG) surgery, either “onpump” or “off-pump,” no sooner than 48 hours from randomization but no longer than 7 days from randomization, with patient to remain hospitalized until planned CABG. 4. Have received a thienopyridine (at least 75 mg of clopidogrel 500 mg ticlopidine, or 10mg prasugrel) within 72 hours prior to enrollment in the study for either: 1. the treatment of an acute coronary syndrome, regardless of time from ACS, and/or 2. as long-term preventative therapy following drug-eluting or bare metal stent treatment. |
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E.4 | Principal exclusion criteria |
1. Confirmed of suspected pregnancy (if woman of child-bearing potential) or lactating females 2. Cerebrovascular accident within one year 3. Intracranial neoplasm or history of intracranial surgery 4. History of bleeding diathesis 5. Thrombocytopenia (platelet count of less than 100,000/μL) 6. Known International Normalized Ratio (INR) greater than 1.5 at screening. 7. Requirement for dialysis treatment (hemodialysis or peritoneal) 8. Estimated Glomeular filtration rate eGFR <30 ml/min 9. Administration of abciximab within 24 hours of randomization or administration of eptifibitide or tirofiban within 12 hours of randomization. 10. Plans to continue oral anticoagulant, thienopyridine or GPIIb/IIIa antagonist therapy in the pre-operative period. 11. Known or suspected coagulopathy 12. Refusal to receive blood transfusion 13. Receipt of fibrinolytic therapy in the 12 hours preceding randomization 14. Allergy, hypersensitivity, or contraindication to cangrelor, mannitol, sorbitol, or microcrystalline cellulose 15. High likelihood of being unavailable for follow-up 16. Participation in other clinical research studies involving the evaluation of other investigational drugs or devices within 30 days of randomization 17. Any disease or condition which, in the judgment of the investigator, would place the patient at undue risk by being enrolled in the trial |
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E.5 End points |
E.5.1 | Primary end point(s) |
Stage I: Open Label lead-in period: The primary endpoint is mantenance of platelet inhibition in at least 80% of patient samples above 60% as determined by VerifyNowTM P2Y12 point of care assay measured during study drug infusion prior to surgery.
Stage II Blinded, randomized period: The primary endpoint is the percentage of patients with PRU<240 as determined by VerifyNowTM P2Y12 point of care assay measured during study drug infusion prior to surgery. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | Yes |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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End of study will be final 30-day visit for the last patient enrolled. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |