"Spot Sign" Selection of Intracerebral Hemorrhage to Guide Hemostatic Therapy (SPOTLIGHT)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Sunnybrook Health Sciences Centre
Sponsor:
Collaborator:
Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):
Dr. David Gladstone, Sunnybrook Health Sciences Centre
ClinicalTrials.gov Identifier:
NCT01359202
First received: May 20, 2011
Last updated: October 15, 2014
Last verified: October 2014
  Purpose

This clinical trial will enroll 110 patients from approximately 15 Canadian stroke centres. Patients coming to the emergency department with bleeding in the brain not due to trauma or other known causes who can be treated within 6 hours of onset will undergo CT angiography using standard CT scanners ("CAT scan"). Those with a "spot sign", a type of marker on the CT scan that shows the brain is still bleeding, will be randomly assigned to a single injection of "factor 7"(a blood clotting drug used in hemophilia) or placebo (inactive saline); patients without a spot sign will not be treated. The researchers will look at how much bleeding happens after the treatments are administered, as well as clinical outcomes such as death and disability. The researchers think that factor 7 will cause the bleeding to stop faster and possibly decrease death and disability.


Condition Intervention Phase
Stroke
Biological: rfVIIa
Other: Standard saline solution
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: "Spot Sign" Selection of Intracerebral Hemorrhage to Guide Hemostatic Therapy: SPOTLIGHT

Resource links provided by NLM:


Further study details as provided by Sunnybrook Health Sciences Centre:

Primary Outcome Measures:
  • ICH size [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    Difference between groups in ICH size on CT scan at 24 hours post-dose, adjusted for baseline ICH size


Secondary Outcome Measures:
  • Feasibility [ Time Frame: 0 ] [ Designated as safety issue: No ]
    Percentage of sites who can meet recruitment targets of 2 patients per site per year; % patients who meet the target time of <45 minutes from emergency department arrival to the start of the scan; % patients who meet the target time of <60 minutes from the end of the CT angiogram to administration of study drug; Local site spot sign interpretation accuracy as judged by central adjudicator; protocol violations

  • Waiver of consent process evaluation/effectiveness [ Time Frame: 4,90 days ] [ Designated as safety issue: No ]
    Waiver of consent use, acceptability, and effect on treatment times. Questionnaire will be administed to subject/LAR at 4 days and 90 days.

  • Acute blood pressure control [ Time Frame: 1hr ] [ Designated as safety issue: No ]
    % subjects where blood pressure control was acheived, defined as achieving systolic BP <180 mmHg within 1 hour post-randomization

  • Thromboembolic events [ Time Frame: 4 days ] [ Designated as safety issue: Yes ]
    Incidence of myocardial infarction and ischemic stroke within 4 days; any other arterial or venous thromboembolic SAEs within 4 days

  • Mortality [ Time Frame: 90 days ] [ Designated as safety issue: Yes ]
    90-day mortality rate

  • Unstable angina [ Time Frame: 4 days ] [ Designated as safety issue: Yes ]
    Unstable angina w/in 4 days of treatment

  • Troponin increase [ Time Frame: 4 days ] [ Designated as safety issue: Yes ]
    Troponin rise above upper limit of normal within 4 days (without clinical symptoms or ECG evidence of acute coronary syndrome)

  • DVT [ Time Frame: 4 days ] [ Designated as safety issue: Yes ]
    Deep venous thrombosis (DVT) within 4 days

  • Pulmonary embolism [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
    PE within 30 days

  • Cognition [ Time Frame: 90 days, 1 year ] [ Designated as safety issue: No ]
    Montreal Cognitive Assessment (MoCA) and Stroke Impact Scale at 90 days and 1 year.

  • Disability [ Time Frame: 90 d, 1 year ] [ Designated as safety issue: Yes ]
    Proportion of subjects with modified Rankin score 5-6 (death or severe disability) at 90 days and 1 year


Estimated Enrollment: 110
Study Start Date: May 2011
Estimated Study Completion Date: August 2016
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Niastase RT
Niastase RT 80ug/kg IV bolus
Biological: rfVIIa
80ug/kg IV bolus
Other Name: Niastase RT
Placebo Comparator: Placebo
saline IV bolus
Other: Standard saline solution
Saline
Other Name: Saline solution sourced from local hospital

Detailed Description:

This phase II double blind RCT will enroll 110 patients from approximately 15 Canadian stroke centres. Acute ICH patients who can be treated within 6 hours of onset will undergo CT angiography using standard CT procedures. Those with a spot sign will be randomly assigned in a 1:1 ratio to a single injection of rFVIIa 80 µg/kg or placebo; patients without a spot sign will not be treated. The primary endpoint is ICH expansion within 24 hours.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • Acute spontaneous primary supratentorial ICH diagnosed by CT scan.
  • Presence of a spot sign within the hematoma on CTA source images
  • Baseline ICH volume 3-90 ml
  • Age 18 or older
  • Investigator is able to randomize and administer study drug as soon as possible within a target of 60 minutes after CT angiogram and no later than 6 hours after stroke symptom onset (using the "last seen normal" principle).
  • Plan to provide full medical care for at least 24 hours
  • Assent-consent from patient or LAR prior to enrolment, or a waiver of consent (where REB approved) if patient/LAR assent-consent is not possible prior to enrolment.

Exclusion Criteria

  • Brainstem or cerebellar hemorrhage.
  • ICH secondary to known or suspected trauma, aneurysm, vascular malformation, hemorrhagic conversion of ischemic stroke, venous sinus thrombosis, thrombolytic treatment, tumour, or infection; or an in-hospital ICH or ICH as a result of any in-hospital procedure or illness.
  • Baseline brain imaging shows evidence of acute or subacute ischemic stroke (chronic infarcts are not an exclusion).
  • Contrast administration within the previous 24 hours.
  • Evidence of thromboembolic risk factors, defined as any of the following: known history within the past 6 months of any of the following: (a) myocardial infarction, (b) coronary artery bypass surgery, (c) angina, (d) ischemic stroke, (e) transient ischemic attack, (f) carotid endarterectomy, (g) cerebral bypass surgery, (h) deep venous thrombosis, (i) pulmonary embolism, (j) any vascular angioplasty, stenting (coronary, peripheral vascular or cerebrovascular) or filter (e.g. vena cava filter);(k) prosthetic cardiac valve; and/or (l) known history of a high-risk thrombophilia (e.g. antithrombin III deficiency, antiphospholipid antibody syndrome, protein C deficiency, etc.)
  • Known hereditary (e.g. hemophilia) or acquired hemorrhagic diathesis or coagulation factor deficiency.
  • Any condition known that the investigator feels would pose a significant hazard if rFVIIa were administered.
  • Planned surgery for ICH within 24 hours (placement of intraventricular catheter is not an exclusion).
  • Planned withdrawal of care before 24 hours post-ICH onset.
  • Known participation in another therapeutic trial.
  • Known allergy or other contraindication to iodinated contrast dye.
  • Known or suspected hypersensitivity to the trial product.
  • Known unfractionated heparin use - must check PTT and exclude if elevated above upper limit of local lab's reference range.
  • Known low-molecular weight heparin, heparinoid, factor X inhibitor, or direct thrombin inhibitor use within previous 7 days.
  • Known GPIIb/IIIa antagonist use in previous 2 weeks.
  • Known warfarin (or other anticoagulant) therapy with INR >1.40. Note: if the patient is suspected to have cirrhosis, study staff are to wait for the INR value prior to dosing, and ensure not to enroll the patient if the INR value is >1.40. Otherwise the physician should use their discretion if they believe the patient is not at risk for elevated INR.
  • Concurrent or planned treatment with prothrombin complex concentrate, vitamin K, fresh frozen plasma, or platelet transfusion.
  • Pregnancy or lactation. Women of childbearing potential must have a negative pregnancy test prior to randomization.
  • Current clinical symptoms suggestive of acute coronary ischemia (e.g. chest pain).
  • Baseline ECG evidence of acute coronary ischemia (e.g. ST elevation in 2 contiguous leads, new LBBB, ST depression).
  • Baseline platelet count <50,000 or INR >1.40 or elevated PTT
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01359202

Contacts
Contact: David J Gladstone, MD 416-480-4866 david.gladstone@sunnybrook.ca

Locations
Canada, Alberta
Foothills Medical Centre Recruiting
Calgary, Alberta, Canada, T2N 2T9
Principal Investigator: Andrew Demchuk, MD         
Sub-Investigator: Michael Hill, MD         
Walter C. Mackenzie Health Sciences Centre Recruiting
Edmonton, Alberta, Canada
Principal Investigator: Ken Butcher, MD         
Canada, British Columbia
Vancouver General Hospital Recruiting
Vancouver, British Columbia, Canada, V5Z 1N1
Principal Investigator: Samuel Yip, MD         
Vancouver Island Health Authority Not yet recruiting
Victoria, British Columbia, Canada, V8R 1J8
Principal Investigator: Andrew Penn, MD         
Canada, Ontario
Hamilton HSC Recruiting
Hamilton, Ontario, Canada
Principal Investigator: Demetrios Sahlas, MD         
Kingston General Hospital Recruiting
Kingston, Ontario, Canada, KZL 2V7
Principal Investigator: Albert Jin, MD         
London Health Sciences Centre Recruiting
London, Ontario, Canada
Principal Investigator: Richard Chan, MD         
Trillium Health Centre Recruiting
Mississauga, Ontario, Canada
Principal Investigator: Manu Mehdiratta, MD         
The Ottawa Hospital Recruiting
Ottawa, Ontario, Canada
Principal Investigator: Dar Dowlatshahi, MD         
Sunnybrook Health Sciences Centre Recruiting
Toronto, Ontario, Canada
Principal Investigator: Richard Swartz, MD         
Sub-Investigator: David Gladstone, MD         
Toronto Western Hospital Recruiting
Toronto, Ontario, Canada, M5T 2S8
Principal Investigator: Martin Del Campo, MD         
St. Michael's Hospital Recruiting
Toronto, Ontario, Canada
Principal Investigator: Daniel Selchen, MD         
Canada, Quebec
Hôpital Charles Le Moyne Recruiting
Greenfield Park, Quebec, Canada, J4V 2H1
Principal Investigator: Jean-Martin Boulanger, MD         
Montreal Neurological Institute Not yet recruiting
Montreal, Quebec, Canada
Principal Investigator: Jeanne Teitelbaum, MD         
Centre hospitalier de l'Université de Montréal Recruiting
Montreal, Quebec, Canada
Principal Investigator: Yan Deschaintre, MD         
Sponsors and Collaborators
Dr. David Gladstone
Canadian Institutes of Health Research (CIHR)
Investigators
Principal Investigator: David J Gladstone, MD Sunnybrook Health Sciences Centre
Principal Investigator: Richard Aviv, MD Sunnybrook Health Sciences Centre
Principal Investigator: Andrew Demchuk, MD University of Calgary
  More Information

No publications provided

Responsible Party: Dr. David Gladstone, Principal Investigator - Sponsor, Sunnybrook Health Sciences Centre
ClinicalTrials.gov Identifier: NCT01359202     History of Changes
Other Study ID Numbers: Spotlight002
Study First Received: May 20, 2011
Last Updated: October 15, 2014
Health Authority: Canada: Health Canada

Keywords provided by Sunnybrook Health Sciences Centre:
Stroke
ICH
Intracerebral hemorrhage
acute stroke
rfVIIa
Niastase

Additional relevant MeSH terms:
Cerebral Hemorrhage
Hemorrhage
Brain Diseases
Cardiovascular Diseases
Central Nervous System Diseases
Cerebrovascular Disorders
Intracranial Hemorrhages
Nervous System Diseases
Pathologic Processes
Vascular Diseases
Hemostatics
Pharmaceutical Solutions
Coagulants
Hematologic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014