Effect of ARC1779 on Cerebral Microembolism in Patients Undergoing Carotid Endarterectomy - Full Text View

Purpose

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.

Condition	Intervention	Phase
Intracranial Embolism Cerebral Thromboembolism Carotid Stenosis	Drug: ARC1779 Injection Drug: Placebo (normal saline)	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment
Official Title:	A Study of the Effect of ARC1779 Injection on Cerebral Microembolism in Patients Undergoing Carotid Endarterectomy

Further study details as provided by Archemix Corp.:

Primary Outcome Measures:

To determine the effect of ARC1779 Injection on the number of microembolic signals detected by transcranial Doppler (TCD) in the immediate postoperative period [ Time Frame: Immediate Post-Operative Period ] [ Designated as safety issue: No ]
To evaluate the safety of ARC1779 Injection with respect to bleeding risk in patients in the perioperative period. [ Time Frame: Perioperative Period ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To determine the effect of ARC1779 on the incidence of new ischemic lesions detectable with diffusion-weighted magnetic resonance imaging (MRI) after carotid endarterectomy [ Time Frame: Up to 7 Days ] [ Designated as safety issue: No ]
To determine the general safety and tolerability of ARC1779 Injection in this surgical population [ Time Frame: Up to 7 Days ] [ Designated as safety issue: Yes ]
To assess laboratory parameters related to ARC1779 pharmacokinetics (PK) and pharmacodynamics (PD) [ Time Frame: Up to 7 Days ] [ Designated as safety issue: Yes ]
To assess the relationships among ARC1779 PD, PK, and the frequency of cerebral microembolism [ Time Frame: Up to 7 Days ] [ Designated as safety issue: Yes ]
To assess the relationships among ARC1779 PD, PK, and safety parameters. [ Time Frame: Up to 7 Days ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	100
Study Start Date:	February 2009
Estimated Study Completion Date:	April 2010
Primary Completion Date:	January 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 1 ARC1779 Injection	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 Comparator: 2 Placebo (normal saline)	Drug: 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.

Arms

Assigned Interventions

Active Comparator: 1

ARC1779 Injection

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 Comparator: 2

Placebo (normal saline)

Drug: 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.

Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00742612

Locations

United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, Texas
Eddy Scurlock Stroke Center - Methodist Hospital
Houston, Texas, United States, 77030
United Kingdom
Addenbrooke's Hospital, Department of Vascular Surgery
Cambridge, United Kingdom, CB2 0QQ
University Hospitals Coventry and Warwickshire NHS TRUST
Coventry, United Kingdom, CV2 2DX
Leeds General Infirmary
Leeds, United Kingdom, LS1 3EX
St. George's, University of London, Cranmer Terrace
London, United Kingdom, SW17 ORE
University Hospital of South Manchester, Wythenshawe Hospital, Southmoor Road
Manchester, United Kingdom, M23 9LT

Sponsors and Collaborators

Archemix Corp.

St George's, University of London

Investigators

Principal Investigator:

Hugh Markus, MD

St George's, University of London

More Information

No publications provided by Archemix Corp.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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. Epub 2011 Jun 23.

Responsible Party:	James Gilbert, MD./Chief Medical Officer, Archemix Corp.
ClinicalTrials.gov Identifier:	NCT00742612 History of Changes
Other Study ID Numbers:	ARC1779-008
Study First Received:	August 25, 2008
Last Updated:	February 9, 2010
Health Authority:	United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Archemix Corp.:

Carotid Endarterectomy
von Willebrand Factor
Microembolic Signal

Additional relevant MeSH terms:

Embolism and Thrombosis
Intracranial Embolism and Thrombosis
Carotid Stenosis
Embolism
Thromboembolism
Intracranial Embolism
Carotid Artery Diseases
Cerebrovascular Disorders

Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Thrombosis

ClinicalTrials.gov processed this record on May 19, 2013