Effect of ARC1779 on Cerebral Microembolism in Patients Undergoing Carotid Endarterectomy

Carotid Stenosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00742612
• Other study ID #: ARC1779-008
• Status: Terminated
• Phase: Phase 2
• First received: August 25, 2008
• Last updated: February 9, 2010
• Start date: February 2009
• Est. completion date: April 2010

Study information

• Verified date: July 2009
• Source: Archemix Corp.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 100
• Est. completion date: April 2010
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carotid Stenosis
• Cerebral Thromboembolism
• Intracranial Embolism
• Thromboembolism

Intervention

Drug:
• ARC1779 Injection
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.
• Placebo (normal saline)
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.

Locations

Country	Name	City	State
United Kingdom	Addenbrooke's Hospital, Department of Vascular Surgery	Cambridge
United Kingdom	University Hospitals Coventry and Warwickshire NHS TRUST	Coventry
United Kingdom	Leeds General Infirmary	Leeds
United Kingdom	St. George's, University of London, Cranmer Terrace	London
United Kingdom	University Hospital of South Manchester, Wythenshawe Hospital, Southmoor Road	Manchester
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Eddy Scurlock Stroke Center - Methodist Hospital	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Archemix Corp.	St George's, University of London

Countries where clinical trial is conducted

United States,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	To evaluate the safety of ARC1779 Injection with respect to bleeding risk in patients in the perioperative period.		Perioperative Period	Yes
Secondary	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	No
Secondary	To determine the general safety and tolerability of ARC1779 Injection in this surgical population		Up to 7 Days	Yes
Secondary	To assess laboratory parameters related to ARC1779 pharmacokinetics (PK) and pharmacodynamics (PD)		Up to 7 Days	Yes
Secondary	To assess the relationships among ARC1779 PD, PK, and the frequency of cerebral microembolism		Up to 7 Days	Yes
Secondary	To assess the relationships among ARC1779 PD, PK, and safety parameters.		Up to 7 Days	Yes