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

NCT ID: NCT01359202

Last Updated: 2018-10-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-05-31
• Study Completion Date: 2018-10-03

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.

Conditions

Stroke

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Niastase RT

Niastase RT 80ug/kg IV bolus

Group Type: ACTIVE_COMPARATOR

rfVIIa

Intervention Type: BIOLOGICAL

80ug/kg IV bolus

Placebo

saline IV bolus

Group Type: PLACEBO_COMPARATOR

Standard saline solution

Intervention Type: OTHER

Saline

Interventions

rfVIIa

80ug/kg IV bolus

Intervention Type: BIOLOGICAL

Standard saline solution

Saline

Intervention Type: OTHER

Other Intervention Names

Niastase RT; Saline solution sourced from local hospital

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

Dr. David Gladstone

OTHER

Sponsor Role: lead

Responsible Party

Dr. David Gladstone

Principal Investigator - Sponsor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

David J Gladstone, MD

Role: PRINCIPAL_INVESTIGATOR

Sunnybrook Health Sciences Centre

Richard Aviv, MD

Role: PRINCIPAL_INVESTIGATOR

Sunnybrook Health Sciences Centre

Andrew Demchuk, MD

Role: PRINCIPAL_INVESTIGATOR

University of Calgary

Locations

Foothills Medical Centre

Calgary, Alberta, Canada

Walter C. Mackenzie Health Sciences Centre

Edmonton, Alberta, Canada

Vancouver General Hospital

Vancouver, British Columbia, Canada

Vancouver Island Health Authority

Victoria, British Columbia, Canada

Hamilton HSC

Hamilton, Ontario, Canada

Kingston General Hospital

Kingston, Ontario, Canada

London Health Sciences Centre

London, Ontario, Canada

Trillium Health Centre

Mississauga, Ontario, Canada

The Ottawa Hospital

Ottawa, Ontario, Canada

Toronto Western Hospital

Toronto, Ontario, Canada

St. Michael's Hospital

Toronto, Ontario, Canada

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Hôpital Charles Le Moyne

Greenfield Park, Quebec, Canada

Centre hospitalier de l'Université de Montréal

Montreal, Quebec, Canada

Montreal Neurological Institute

Montreal, Quebec, Canada

Countries

Canada

References

Al-Ajlan FS, Gladstone DJ, Song D, Thorpe KE, Swartz RH, Butcher KS, Del Campo M, Dowlatshahi D, Gensicke H, Lee GJ, Flaherty ML, Hill MD, Aviv RI, Demchuk AM; SPOTLIGHT Investigators. Time Course of Early Hematoma Expansion in Acute Spot-Sign Positive Intracerebral Hemorrhage: Prespecified Analysis of the SPOTLIGHT Randomized Clinical Trial. Stroke. 2023 Mar;54(3):715-721. doi: 10.1161/STROKEAHA.121.038475. Epub 2023 Feb 9.

Reference Type: DERIVED

PMID: 36756899 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31424491 (View on PubMed)

Other Identifiers

Spotlight002

Identifier Type: -

Identifier Source: org_study_id