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Effect of ARC1779 on Cerebral Microembolism in Patients Undergoing Carotid Endarterectomy

Primary Purpose

Intracranial Embolism, Cerebral Thromboembolism, Carotid Stenosis

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
ARC1779 Injection
Placebo (normal saline)
Sponsored by
Archemix Corp.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Intracranial Embolism focused on measuring Carotid Endarterectomy, von Willebrand Factor, Microembolic Signal

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Hackensack University Medical Center
  • Eddy Scurlock Stroke Center - Methodist Hospital
  • Addenbrooke's Hospital, Department of Vascular Surgery
  • University Hospitals Coventry and Warwickshire NHS TRUST
  • Leeds General Infirmary
  • St. George's, University of London, Cranmer Terrace
  • University Hospital of South Manchester, Wythenshawe Hospital, Southmoor Road

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

1

2

Arm Description

ARC1779 Injection

Placebo (normal saline)

Outcomes

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
To evaluate the safety of ARC1779 Injection with respect to bleeding risk in patients in the perioperative period.

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
To determine the general safety and tolerability of ARC1779 Injection in this surgical population
To assess laboratory parameters related to ARC1779 pharmacokinetics (PK) and pharmacodynamics (PD)
To assess the relationships among ARC1779 PD, PK, and the frequency of cerebral microembolism
To assess the relationships among ARC1779 PD, PK, and safety parameters.

Full Information

First Posted
August 25, 2008
Last Updated
February 9, 2010
Sponsor
Archemix Corp.
Collaborators
St George's, University of London
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1. Study Identification

Unique Protocol Identification Number
NCT00742612
Brief Title
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

2. Study Status

Record Verification Date
July 2009
Overall Recruitment Status
Terminated
Why Stopped
Enrollment slower than expected
Study Start Date
February 2009 (undefined)
Primary Completion Date
January 2010 (Actual)
Study Completion Date
April 2010 (Anticipated)

3. Sponsor/Collaborators

Name of the Sponsor
Archemix Corp.
Collaborators
St George's, University of London

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Intracranial Embolism, Cerebral Thromboembolism, Carotid Stenosis
Keywords
Carotid Endarterectomy, von Willebrand Factor, Microembolic Signal

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Active Comparator
Arm Description
ARC1779 Injection
Arm Title
2
Arm Type
Placebo Comparator
Arm Description
Placebo (normal saline)
Intervention Type
Drug
Intervention Name(s)
ARC1779 Injection
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo (normal saline)
Intervention Description
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.
Primary Outcome Measure Information:
Title
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
Title
To evaluate the safety of ARC1779 Injection with respect to bleeding risk in patients in the perioperative period.
Time Frame
Perioperative Period
Secondary Outcome Measure Information:
Title
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
Title
To determine the general safety and tolerability of ARC1779 Injection in this surgical population
Time Frame
Up to 7 Days
Title
To assess laboratory parameters related to ARC1779 pharmacokinetics (PK) and pharmacodynamics (PD)
Time Frame
Up to 7 Days
Title
To assess the relationships among ARC1779 PD, PK, and the frequency of cerebral microembolism
Time Frame
Up to 7 Days
Title
To assess the relationships among ARC1779 PD, PK, and safety parameters.
Time Frame
Up to 7 Days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hugh Markus, MD
Organizational Affiliation
St George's, University of London
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Eddy Scurlock Stroke Center - Methodist Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Addenbrooke's Hospital, Department of Vascular Surgery
City
Cambridge
ZIP/Postal Code
CB2 0QQ
Country
United Kingdom
Facility Name
University Hospitals Coventry and Warwickshire NHS TRUST
City
Coventry
ZIP/Postal Code
CV2 2DX
Country
United Kingdom
Facility Name
Leeds General Infirmary
City
Leeds
ZIP/Postal Code
LS1 3EX
Country
United Kingdom
Facility Name
St. George's, University of London, Cranmer Terrace
City
London
ZIP/Postal Code
SW17 ORE
Country
United Kingdom
Facility Name
University Hospital of South Manchester, Wythenshawe Hospital, Southmoor Road
City
Manchester
ZIP/Postal Code
M23 9LT
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
30957581
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.
Results Reference
derived
PubMed Identifier
21700934
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.
Results Reference
derived

Learn more about this trial

Effect of ARC1779 on Cerebral Microembolism in Patients Undergoing Carotid Endarterectomy

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