Effect of ARC1779 on Cerebral Microembolism in Patients Undergoing Carotid Endarterectomy

NCT00742612 | Terminated Phase 2 DMC

• 1 other identifier: ARC1779-008
• Study Type: interventional
• Target: 100
• Locations: 2 countries
• Sites: 7

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.

Conditions

Intracranial Embolism; Cerebral Thromboembolism; Carotid Stenosis

Keywords

Carotid Endarterectomy; von Willebrand Factor; Microembolic Signal

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (5)

• 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

Study Arms (2)

1

ACTIVE COMPARATOR

ARC1779 Injection

Drug: ARC1779 Injection

2

PLACEBO COMPARATOR

Placebo (normal saline)

Drug: Placebo (normal saline)

Interventions

ARC1779 Injection DRUG

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.

1

Placebo (normal saline) DRUG

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.

2

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Archemix Corp.: lead
• St George's, University of London: collaborator

Study Sites (7)

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Eddy Scurlock Stroke Center - Methodist Hospital

Houston, Texas, 77030, United States

Location

Addenbrooke's Hospital, Department of Vascular Surgery

Cambridge, CB2 0QQ, United Kingdom

Location

University Hospitals Coventry and Warwickshire NHS TRUST

Coventry, CV2 2DX, United Kingdom

Location

Leeds General Infirmary

Leeds, LS1 3EX, United Kingdom

Location

St. George's, University of London, Cranmer Terrace

London, SW17 ORE, United Kingdom

Location

University Hospital of South Manchester, Wythenshawe Hospital, Southmoor Road

Manchester, M23 9LT, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 30957581 DERIVED

• 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.

  PMID: 21700934 DERIVED

MeSH Terms

Conditions

Intracranial Embolism; Carotid Stenosis

Interventions

ARC 1779; Saline Solution

Condition Hierarchy (Ancestors)

Intracranial Embolism and Thrombosis; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Thromboembolism; Embolism and Thrombosis; Carotid Artery Diseases; Arterial Occlusive Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Hugh Markus, MD

  St George's, University of London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: August 25, 2008
• First Posted: August 27, 2008
• Study Start: February 1, 2009
• Primary Completion: January 1, 2010
• Study Completion: April 1, 2010
• Last Updated: February 10, 2010

Record last verified: 2009-07

Locations

US (2); GB (5)