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

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

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.

Study Overview

• Status: Completed
• Conditions: Stroke
• Intervention / Treatment: Biological: rfVIIa; Other: Standard saline solution

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.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • Foothills Medical Centre
    • Edmonton, Alberta, Canada
      • Walter C. Mackenzie Health Sciences Centre
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1N1
      • Vancouver General Hospital
    • Victoria, British Columbia, Canada, V8R 1J8
      • Vancouver Island Health Authority
  • Ontario
    • Hamilton, Ontario, Canada
      • Hamilton HSC
    • Kingston, Ontario, Canada, KZL 2V7
      • Kingston General Hospital
    • London, Ontario, Canada
      • London Health Sciences Centre
    • Mississauga, Ontario, Canada
      • Trillium Health Centre
    • Ottawa, Ontario, Canada
      • The Ottawa Hospital
    • Toronto, Ontario, Canada, M5T 2S8
      • Toronto Western Hospital
    • Toronto, Ontario, Canada
      • St. Michael's Hospital
    • Toronto, Ontario, Canada
      • Sunnybrook Health Sciences Centre
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2H1
      • Hopital Charles Le Moyne
    • Montreal, Quebec, Canada
      • Centre Hospitalier de l'Universite de Montreal
    • Montreal, Quebec, Canada
      • Montreal Neurological Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Niastase RT; Niastase RT 80ug/kg IV bolus	Biological: rfVIIa; 80ug/kg IV bolus; Other Names: Niastase RT
Placebo Comparator: Placebo; saline IV bolus	Other: Standard saline solution; Saline; Other Names: Saline solution sourced from local hospital

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ICH size	Difference between groups in ICH size on CT scan at 24 hours post-dose, adjusted for baseline ICH size	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility	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	Waiver of consent use, acceptability, and effect on treatment times. Questionnaire will be administed to subject/LAR at 4 days and 90 days.	4,90 days
Acute blood pressure control	% subjects where blood pressure control was acheived, defined as achieving systolic BP <180 mmHg within 1 hour post-randomization	1hr
Thromboembolic events	Incidence of myocardial infarction and ischemic stroke within 4 days; any other arterial or venous thromboembolic SAEs within 4 days	4 days
Mortality	90-day mortality rate	90 days
Unstable angina	Unstable angina w/in 4 days of treatment	4 days
Troponin increase	Troponin rise above upper limit of normal within 4 days (without clinical symptoms or ECG evidence of acute coronary syndrome)	4 days
DVT	Deep venous thrombosis (DVT) within 4 days	4 days
Pulmonary embolism	PE within 30 days	30 days
Cognition	Montreal Cognitive Assessment (MoCA) and Stroke Impact Scale at 90 days and 1 year.	90 days, 1 year
Disability	Proportion of subjects with modified Rankin score 5-6 (death or severe disability) at 90 days and 1 year	90 d, 1 year

Collaborators and Investigators

• Sponsor: Dr. David Gladstone
• Collaborators: 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

Publications and helpful links

General Publications

• Gladstone DJ, Aviv RI, Demchuk AM, Hill MD, Thorpe KE, Khoury JC, Sucharew HJ, Al-Ajlan F, Butcher K, Dowlatshahi D, Gubitz G, De Masi S, Hall J, Gregg D, Mamdani M, Shamy M, Swartz RH, Del Campo CM, Cucchiara B, Panagos P, Goldstein JN, Carrozzella J, Jauch EC, Broderick JP, Flaherty ML; SPOTLIGHT and STOP-IT Investigators and Coordinators. Effect of Recombinant Activated Coagulation Factor VII on Hemorrhage Expansion Among Patients With Spot Sign-Positive Acute Intracerebral Hemorrhage: The SPOTLIGHT and STOP-IT Randomized Clinical Trials. JAMA Neurol. 2019 Dec 1;76(12):1493-1501. doi: 10.1001/jamaneurol.2019.2636.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2011
• Primary Completion (Actual): June 30, 2018
• Study Completion (Actual): October 3, 2018

Study Registration Dates

• First Submitted: May 20, 2011
• First Submitted That Met QC Criteria: May 20, 2011
• First Posted (Estimate): May 24, 2011

Study Record Updates

• Last Update Posted (Actual): October 5, 2018
• Last Update Submitted That Met QC Criteria: October 3, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Stroke; ICH; Intracerebral hemorrhage; acute stroke; rfVIIa; Niastase
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intracranial Hemorrhages; Hemorrhage; Cerebral Hemorrhage; Pharmaceutical Solutions
• Other Study ID Numbers: Spotlight002