E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients undergoing carotid endarterectomy, |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10007692 |
E.1.2 | Term | Carotid endarterectomy |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary Objectives • To determine the effect of a continuous intravenous infusion of ARC1779 Injection on the number of microembolic signals detected by transcranial Doppler (TCD) in the immediate postoperative period; • To evaluate the safety of ARC1779 Injection with respect to bleeding risk in patients in the perioperative period. |
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E.2.2 | Secondary objectives of the trial |
Secondary Objectives • To determine the effect of ARC1779 on the incidence of new ischemic lesions detectable with diffusion-weighted magnetic resonance imaging (MRI) after carotid endarterectomy; • To determine the general safety and tolerability of ARC1779 Injection in this surgical population; • To assess laboratory parameters related to ARC1779 pharmacokinetics (PK) and pharmacodynamics (PD); • To assess the relationships among ARC1779 PD, PK, and the frequency of cerebral microembolism; • To assess the relationships among ARC1779 PD, PK, and safety parameters. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion Criteria • Male or female patients; • 18 to 85 years of age; • Carotid stenosis (either symptomatic or asymptomatic); • Planned carotid endarterectomy; • Female patients must be non-pregnant and willing to use effective, redundant methods of contraception (i.e., for both self and male partner) throughout the study and for at least 30 days after discontinuation of study drug treatment; • Male patients must agree to use a medically acceptable contraceptive (abstinence or use of a condom with spermicide) throughout the study and for at least 30 days after discontinuation of study drug treatment; • All patients must be capable of understanding and complying with the protocol and must have signed the informed consent document. |
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E.4 | Principal exclusion criteria |
Exclusion Criteria • Lack of acoustic window allowing TCD recordings; • Unable or unwilling to consent; • Medical condition unsuitable for planned carotid endarterectomy surgery; • Metallic prosthetic cardiac valve; • Recent (<4 weeks) ischemic stroke involving >1/3 of the middle cerebral artery (MCA) territory; • Any history of hemorrhagic stroke; • Thrombocytopenia; • Coagulopathy; • Recent or current bleeding disorder or other medical problem associated with an increased risk of bleeding; • Trauma or surgery within preceding 30 days; • Use of warfarin or any chronic antithrombotic therapy other than acetylsalicylic acid and/or dipyridamole; patients previously treated with warfarin are eligible if the drug has been discontinued and the INR prior to randomization has returned to <1.3; • Use of clopidogrel, unless it has been discontinued at least 5 days prior to randomization; • Fibrinolytic or glycoprotein (GP) IIb/IIIa inhibitor treatment within the preceding 24 hours. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Efficacy Variable • Number of microembolic signals (MES) detected by TCD during the 3 hours immediately following restoration of carotid circulation. Secondary Efficacy Variables • Hourly number of MES during each of the 3 hours of postoperative recording; • Proportion of patients without MES overall, and in each of the 3 hours of postoperative recording; • Kaplan-Meier analysis of freedom from MES; • Mean intensity of embolic signals in patients with MES; • Proportion of patients with >10 MES per hour; • Group mean number of new lesions on postoperative MRI by diffusion-weighted imaging (DWI); • Proportion of patients with new postoperative DWI lesions; • Clinical transient ischemic attack (TIA) and stroke during the first postoperative week; • Group mean concentration of a biomarker for central nervous system (CNS) injury (S100 ). |
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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 | No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
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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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 | 22 |
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 | 22 |
E.8.9.2 | In all countries concerned by the trial days | 0 |