Clinical trial NCT00742612: Effect of ARC1779 on Cerebral Microembolism in Patients Undergoing Carotid Endarterectomy
Official title: A Study of the Effect of ARC1779 Injection on Cerebral Microembolism in Patients Undergoing Carotid Endarterectomy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Intracranial Embolism
Cerebral Thromboembolism
Carotid Stenosis
Keywords: Carotid Endarterectomy
von Willebrand Factor
Microembolic Signal
Lead sponsor: Archemix Corp.
Sponsor class: INDUSTRY
Collaborators: name: St George's, University of London
First posted: 2008-08-27
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: To determine the effect of ARC1779 Injection on the number of microembolic signals detected by transcranial Doppler (TCD) in the immediate postoperative period
timeFrame: Immediate Post-Operative Period
measure: To evaluate the safety of ARC1779 Injection with respect to bleeding risk in patients in the perioperative period.
timeFrame: Perioperative Period
Secondary outcomes:
measure: To determine the effect of ARC1779 on the incidence of new ischemic lesions detectable with diffusion-weighted magnetic resonance imaging (MRI) after carotid endarterectomy
timeFrame: Up to 7 Days
measure: To determine the general safety and tolerability of ARC1779 Injection in this surgical population
timeFrame: Up to 7 Days
measure: To assess laboratory parameters related to ARC1779 pharmacokinetics (PK) and pharmacodynamics (PD)
timeFrame: Up to 7 Days
measure: To assess the relationships among ARC1779 PD, PK, and the frequency of cerebral microembolism
timeFrame: Up to 7 Days
measure: To assess the relationships among ARC1779 PD, PK, and safety parameters.
timeFrame: Up to 7 Days
Other outcomes:
Locations:
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Houston
country: United States
facility: Eddy Scurlock Stroke Center - Methodist Hospital
state: Texas
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital, Department of Vascular Surgery
city: Coventry
country: United Kingdom
facility: University Hospitals Coventry and Warwickshire NHS TRUST
city: Leeds
country: United Kingdom
facility: Leeds General Infirmary
city: London
country: United Kingdom
facility: St. George's, University of London, Cranmer Terrace
city: Manchester
country: United Kingdom
facility: University Hospital of South Manchester, Wythenshawe Hospital, Southmoor Road
Study officials:
affiliation: St George's, University of London
name: Hugh Markus, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Park EJ, Choi J, Lee KC, Na DH. Emerging PEGylated non-biologic drugs. Expert Opin Emerg Drugs. 2019 Jun;24(2):107-119. doi: 10.1080/14728214.2019.1604684. Epub 2019 Apr 19.
citation: Markus HS, McCollum C, Imray C, Goulder MA, Gilbert J, King A. The von Willebrand inhibitor ARC1779 reduces cerebral embolization after carotid endarterectomy: a randomized trial. Stroke. 2011 Aug;42(8):2149-53. doi: 10.1161/STROKEAHA.111.616649. Epub 2011 Jun 23.