Effect of ARC1779 on Cerebral Microembolism in Patients Undergoing Carotid Endarterectomy

Study Overview
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Brief Summary
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The purpose of this study is to determine, in patients undergoing carotid endarterectomy, the effect of ARC1779 Injection on the number of microembolic signals detected by transcranial Doppler immediately after surgery. This study will also evaluate the safety of ARC1779 Injection with respect to bleeding risk in patients in the peri-operative (during surgery) period.

Official Title
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A Study of the Effect of ARC1779 Injection on Cerebral Microembolism in Patients Undergoing Carotid Endarterectomy

Conditions
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Intracranial Embolism, Cerebral Thromboembolism, Carotid Stenosis

Intervention / Treatment
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* Drug: ARC1779 Injection
* Drug: Placebo (normal saline)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients; >/= 18 to </= 80 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. Exclusion Criteria: Lack of acoustic window allowing TCD recordings; Unable or unwilling to consent; Metallic prosthetic cardiac valve; Recent (<4 weeks) ischemic stroke involving >1/3 of the MCA territory; Any history of hemorrhagic stroke; Thrombocytopenia; Coagulopathy; Trauma or surgery within preceding 30 days; History of bleeding disorder, gastrointestinal ulcers, or other medical problem associated with an increased risk of bleeding; Use of warfarin and 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 GPIIb/IIIa inhibitor treatment within the preceding 24 hours.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>ARC1779 Injection | Drug: ARC1779 Injection<br>* Study drug treatment will be initiated 1 hour prior to the induction of anesthesia with a loading dose given over 1 hour in 3 successively increasing, 20-minute step infusions. The ARC1779 treatment group will be dosed to achieve a target ARC1779 steady-state plasma concentration of 3 Ug/mL, using a loading dose infusion sequence of 0.0015 mg/kg/min for 20 minutes, 0.003 mg/kg/min for the next 20 minutes, and then 0.006 mg/kg/min for the final 20 minutes; thereafter, their maintenance infusion rate is to be 0.0006 mg/kg/min.<br>|
| Placebo Comparator: 2<br>Placebo (normal saline) | Drug: Placebo (normal saline)<br>* Study drug treatment will be initiated 1 hour prior to the induction of anesthesia with a loading dose given over 1 hour in 3 successively increasing, 20-minute step infusions. The placebo group will be dosed to a steady-state plasma concentration using a loading dose infusion sequence of 0.0015 mg/kg/min for 20 minutes, 0.003 mg/kg/min for the next 20 minutes, and then 0.006 mg/kg/min for the final 20 minutes; thereafter, their maintenance infusion rate is to be 0.0006 mg/kg/min.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the effect of ARC1779 Injection on the number of microembolic signals detected by transcranial Doppler (TCD) in the immediate postoperative period |  | Immediate Post-Operative Period | 
| To evaluate the safety of ARC1779 Injection with respect to bleeding risk in patients in the perioperative period. |  | Perioperative Period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the effect of ARC1779 on the incidence of new ischemic lesions detectable with diffusion-weighted magnetic resonance imaging (MRI) after carotid endarterectomy |  | Up to 7 Days | 
| To determine the general safety and tolerability of ARC1779 Injection in this surgical population |  | Up to 7 Days | 
| To assess laboratory parameters related to ARC1779 pharmacokinetics (PK) and pharmacodynamics (PD) |  | Up to 7 Days | 
| To assess the relationships among ARC1779 PD, PK, and the frequency of cerebral microembolism |  | Up to 7 Days | 
| To assess the relationships among ARC1779 PD, PK, and safety parameters. |  | Up to 7 Days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Carotid Endarterectomy, von Willebrand Factor, Microembolic Signal