'SPOT Sign' seLection of Intracerebral haemorrhage to Guide Haemostatic therapy

Phase 2

Completed

Conditions: Intracerebral hemorrhage (ICH)
Circulatory System
Intracerebral hemorrhage

Registration Number: ISRCTN29749408

Lead Sponsor: Sunnybrook Research Institute (Canada)

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: All

Target Recruitment: 110

Inclusion Criteria

Current inclusion criteria as of 24/04/2014:
1. Acute spontaneous primary supratentorial ICH diagnosed by CT scan
2. Presence of a spot sign within the hematoma on CTA (single-phase, multi-phase, or dynamic CTA). [Note: CTA should ideally be performed immediately after the baseline CT scan. If CTA is going to be delayed more than 20 minutes after the baseline CT, then a new plain head CT must be obtained immediately prior to CTA which will serve as the baseline CT for the study]. A spot sign must meet the following criteria:
2.1. One or more foci of contrast enhancement within the margin of a parenchymal hematoma
2.2. Any size or morphology (shape may be spot-like, linear or serpiginous)
2.3. Spot sign(s) must not have any connection to vessels outside the hematoma
2.4. Hounsfield unit density greater than background hematoma density (density of spot sign is typically >120 Hounsfield units)
2.5. No corresponding density present within the hematoma on non-contrast CT
3. Baseline ICH volume 3-90 ml, estimated using the standard 'abc/2' calculation on the baseline plain head CT
4. Age 18 years or over
5. 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)
6. Plan to provide full medical care for at least 24 hours
7. Consent from patient or LAR prior to enrolment (or a waiver of consent if patient/LAR assent-consent is not possible prior to enrolment, and if REB approved at your site). [Note: full informed consent to be obtained as soon as possible after study treatment administered].

Previous inclusion criteria:
1. Acute spontaneous primary supratentorial ICH diagnosed by CT scan
2. Evidence of active contrast extravasation within the haematoma as defined by the presence of a spot sign on CTA source images. [Note: CTA should ideally be performed immediately after the baseline CT scan. If CTA is going to be delayed more than 20 minutes after the baseline CT, then a new baseline plain head CT must be obtained immediately prior to CTA]. A spot sign must meet the following criteria:
2.1. One or more foci of contrast enhancement within the margin of a parenchymal haematoma
2.2. Any size or morphology (shape may be spot-like, linear or serpiginous)
2.3. Spot sign(s) must not have any connection to vessels outside the haematoma
2.4. Hounsfield unit density at least double that of background haematoma density (density of spot sign is typically greater than 120 Hounsfield units)
2.5. No corresponding density present within the haematoma on non-contrast CT
3. Baseline ICH volume 3 - 70 ml, estimated using the standard abc/2 calculation on the baseline plain head CT
4. Age 18 - 85 years (participants must have had their 18th birthday and not their 86th birthday), males and females
5. Investigator is able to randomise and administer study drug within 60 minutes after CT angiogram and no later than 6 hours after stroke symptom onset (using the last seen normal principle)
6. Assent-consent from patient or LAR prior to enrolment, or a waiver of consent if patient/LAR assent-consent is not possible prior to enrolment. [Note: full informed consent to be obtained as soon as possible after study treatment administered].

Exclusion Criteria

Current exclusion criteria as of 24/04/2014:
Diagnostic/imaging exclusions:
1. Brainstem or cerebellar hemorrhage
2. 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
3. Baseline brain imaging shows evidence of acute or subacute ischemic stroke (chronic infarcts are not an exclusion)
4. Contrast administration within the previous 24 hours

Clinical exclusions:
1. Evidence of thromboembolic risk factors, defined as any of the following: known history within the past 6 months of any of the following: myocardial infarction, coronary artery bypass surgery, angina, ischemic stroke, transient ischemic attack, carotid endarterectomy, cerebral bypass surgery, deep venous thrombosis, pulmonary embolism, vascular angioplasty, stenting (coronary, peripheral vascular or cerebrovascular) or filter (e.g. vena cava filter); prosthetic cardiac valve; and/or known history of a high-risk thrombophilia (e.g. antithrombin III deficiency, antiphospholipid antibody syndrome, protein C deficiency, etc)
2. Known hereditary (e.g. hemophilia) or acquired hemorrhagic diathesis or coagulation factor deficiency
3. Any condition known that the investigator feels would pose a significant hazard if rFVIIa were administered
4. Planned surgery for ICH within 24 hours (placement of intraventricular catheter is not an exclusion)
5. Planned withdrawal of care before 24 hours post-ICH onset
6. Known participation in another therapeutic trial
7. Known allergy or other contraindication to iodinated contrast dye
8. Known or suspected hypersensitivity to the trial product

Medication exclusions:
1. Known unfractionated heparin use ? must check PTT and exclude if elevated above upper limit of local lab?s reference range
2. Known low-molecular weight heparin, heparinoid, factor X inhibitor, or direct thrombin inhibitor use within previous 7 days
3. Known GPIIb/IIIa antagonist use in previous 2 weeks
4. 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
5. Concurrent or planned treatment with prothrombin complex concentrate, vitamin K, fresh frozen plasma, or platelet transfusion

Clinical/laboratory exclusions:
1. Pregnancy or lactation. Women of childbearing potential must have a negative pregnancy test prior to randomization
2. Current clinical symptoms suggestive of acute coronary ischemia (e.g. chest pain)
3. Baseline ECG evidence of acute coronary ischemia (e.g. ST elevation in 2 contiguous leads, new LBBB, ST depression)
4. Baseline platelet count <50,000 or INR >1.40 or elevated PTT [Note: participants can be enrolled without awaiting these results unless a bleeding abnormality or thrombocytopenia is suspected, the participant is known to have been taking warfarin, heparin, or other anticoagulant, or anticoagulation use is uncertain]

Previous exclusion criteria:
Diagnostic/imaging exclusions:
1. Brainstem or cerebellar haemorrhage
2. ICH secondary to known or suspected trauma, aneurysm, vascular malformation, hemorrhagic conversion of ischemic stroke, venous

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
ICH growth within 24 hours between the active drug and placebo. The ICH volume will be measured by analysing the baseline CT scan compared to the CT scan at 24 hours, by means of linear regression. The 24-hour ICH volume will be summarised for each group by descriptive statistics and the adjusted treatment effect and 95% confidence interval will be obtained from the regression model.

Secondary Outcome Measures

Name	Time	Method
Measured by completing CRF forms to capture date and time of study-related assessments such as:<br>1. Blood work<br>2. Informed consent processes<br>3. Vitals<br>4. Well-established grading scales, occurring at regular intervals. The grading scales are already used clinically by many sites, and are all incorporated into this trial. Patients will be assessed at baseline, immediately after dosing, days 1 - 4, 30, 90 and 1 year post based on the following scales: <br>4.1. Glasgow Coma Scale<br>4.2. NIH Stroke Scale<br>4.3. Barthel Index<br>4.4. Modified Rankin Score<br>4.5. MoCA cognitive assessment<br>4.6. Stroke Impact Scale<br>4.7. EQ-5D