Clinical trial NCT01359202: "Spot Sign" Selection of Intracerebral Hemorrhage to Guide Hemostatic Therapy
Official title: "Spot Sign" Selection of Intracerebral Hemorrhage to Guide Hemostatic Therapy: SPOTLIGHT
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Stroke
Keywords: Stroke
ICH
Intracerebral hemorrhage
acute stroke
rfVIIa
Niastase
Lead sponsor: Sunnybrook Health Sciences Centre
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2011-05-24
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: ICH size
timeFrame: 24 hours
Secondary outcomes:
measure: Feasibility
timeFrame: 0
measure: Waiver of consent process evaluation/effectiveness
timeFrame: 4,90 days
measure: Acute blood pressure control
timeFrame: 1hr
measure: Thromboembolic events
timeFrame: 4 days
measure: Mortality
timeFrame: 90 days
measure: Unstable angina
timeFrame: 4 days
measure: Troponin increase
timeFrame: 4 days
measure: DVT
timeFrame: 4 days
measure: Pulmonary embolism
timeFrame: 30 days
measure: Cognition
timeFrame: 90 days, 1 year
measure: Disability
timeFrame: 90 d, 1 year
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Foothills Medical Centre
state: Alberta
city: Edmonton
country: Canada
facility: Walter C. Mackenzie Health Sciences Centre
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Victoria
country: Canada
facility: Vancouver Island Health Authority
state: British Columbia
city: Hamilton
country: Canada
facility: Hamilton HSC
state: Ontario
city: Kingston
country: Canada
facility: Kingston General Hospital
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Mississauga
country: Canada
facility: Trillium Health Centre
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: Toronto Western Hospital
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Greenfield Park
country: Canada
facility: Hôpital Charles Le Moyne
state: Quebec
city: Montreal
country: Canada
facility: Centre hospitalier de l'Université de Montréal
state: Quebec
city: Montreal
country: Canada
facility: Montreal Neurological Institute
state: Quebec
Study officials:
affiliation: Sunnybrook Health Sciences Centre
name: David J Gladstone, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sunnybrook Health Sciences Centre
name: Richard Aviv, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Calgary
name: Andrew Demchuk, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.