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

Sponsors and Collaborators:	Archemix Corp. St George's, University of London
Information provided by:	Archemix Corp.
ClinicalTrials.gov Identifier:	NCT00742612

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 II

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study
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:	November 2008
Estimated Study Completion Date:	December 2009
Estimated Primary Completion Date:	November 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator 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.
2: Placebo Comparator 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

1: Active Comparator

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.

2: Placebo Comparator

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

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

Responsible Party:	Archemix Corp. ( James Gilbert, MD./Chief Medical Officer )
Study ID Numbers:	ARC1779-008
Study First Received:	August 25, 2008
Last Updated:	August 26, 2008
ClinicalTrials.gov Identifier:	NCT00742612
Health Authority:	United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Archemix Corp.:

Carotid Endarterectomy
von Willebrand Factor
Microembolic Signal

Study placed in the following topic categories:

Von Willebrand Disease
Arterial Occlusive Diseases
Vascular Diseases
Central Nervous System Diseases
Constriction, Pathologic
Intracranial Embolism
Brain Diseases
Cerebrovascular Disorders

Intracranial Embolism and Thrombosis
Thromboembolism
Thrombosis
Carotid Stenosis
Embolism and Thrombosis
Embolism
Carotid Artery Diseases
Von Willebrand disease

Additional relevant MeSH terms:

Nervous System Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on January 16, 2009