Overview

This trial has been completed.

Condition intracerebral hemorrhage
Treatments recombinant activated factor vii, placebo
Phase phase 2
Sponsor University of Cincinnati
Collaborator National Institute of Neurological Disorders and Stroke (NINDS)
Start date November 2010
End date April 2016
Trial size 92 participants
Trial identifier NCT00810888, P50NS044283, P50NS044283_STOP_IT

Summary

The purpose of this study is to determine if computed tomography angiography can predict which individuals with intracerebral hemorrhage will experience significant growth in the size of the hemorrhage. For individuals who are at high risk for hemorrhage growth, the study will compare the drug recombinant activated factor VII (rFVIIa) to placebo to determine the effect of rFVIIa on intracerebral hemorrhage growth.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Active Comparator)
Participants with ICH who are determined by CTA to be at high risk for hemorrhage growth (or determined to be CTA "spot sign" positive for contrast leakage within the brain hematoma) will be randomized to receive either rFVIIa at 80 mcg/kg (maximum dose volume 21.3 mL, equivalent to maximum weight of 160 kg) or a placebo .
recombinant activated factor vii
Participants will receive rFVIIa at 80 mcg/kg (maximum dose volume 21.3 mL, equivalent to maximum weight of 160 kg).
(Placebo Comparator)
Participants with ICH who are determined by CTA to be at high risk for hemorrhage growth (or determined to be CTA "spot sign" positive for contrast leakage within the brain hematoma) will be randomized to receive either rFVIIa at 80 mcg/kg or a placebo (maximum dose volume 21.3 mL, equivalent to maximum weight of 160 kg).
placebo
An inactive substance (maximum dose volume 21.3 mL, equivalent to maximum weight of 160 kg)
(No Intervention)
Participants with ICH who are determined by CTA not to be at high risk for hemorrhage growth (determined to be CTA "spot sign" negative) will be enrolled into a prospective observational group.

Primary Outcomes

Measure
Life-threatening thromboembolic complications defined as development of (1) acute myocardial ischemia; (2) acute cerebral ischemia; and (3) acute pulmonary embolism
time frame: through day 4 after completion of study drug
The rate of hematoma growth among spot sign positive subjects at 24 hours, comparing subjects treated with rFVIIa to those treated with placebo. Hematoma growth will be defined as a > 33% or > 6 cc increase in volume.
time frame: at 24 hours
The sensitivity and specificity of the spot sign for predicting hematoma growth
time frame: Baseline head CT scan within 5 hours, followed by a CT angiogram. Hematoma growth determined by comparison with a head CT scan performed at 24 hours.

Secondary Outcomes

Measure
Incidence of other potentially study drug related thromboembolic complications such as deep venous thrombosis and elevations in troponin not associated with ECG changes
time frame: through day 4 after completion of study drug
Ninety-day outcomes among spot positive subjects, dichotomized as modified Rankin Scale score of 0-4 verses 5-6, comparing subjects treated with rFVIIa to those treated with placebo
time frame: 90 days (+/- 7 days) from time of study enrollment
The positive and negative predictive values of the spot sign and the accuracy of the site investigators for correct identification of the spot sign as compared to a blinded study neuroradiologist.
time frame: Baseline head CT scan within 5 hours, followed by a CT angiogram. Hematoma growth determined by comparison with a head CT scan performed at 24 hours.
Rate of total hemorrhage volume growth (hematoma + IVH) among spot-positive subjects.
time frame: 24 hours (+/- 3 hours) from baseline CT scan

Eligibility Criteria

Male or female participants from 18 years up to 80 years old.

Inclusion Criteria: - Acute, spontaneous ICH (including bleeding in cerebellum) diagnosed by non-enhanced CT scan within five hours of symptom onset. (Time of onset is defined as the last time the patient was witnessed to be at baseline (i.e., subjects who have stroke symptoms upon awakening will be considered to have their onset at beginning of sleep) - Age >/= 18 years through 80 years (candidates must have had their 18th birthday, but not had their 81st birthday) - For spot positive patients, dosing of study drug within 90 minutes of enrolling CT scan Exclusion Criteria: - Time of symptom onset of ICH is unknown or more than five hours prior to baseline CT scan, - ICH secondary to known or suspected trauma, aneurysm, vascular malformation, hemorrhagic conversion of ischemic stroke, venous sinus thrombosis, thrombolytic treatment of any condition (e.g., myocardial infarction, cerebral infarction, etc.), CNS tumor or CNS infection - Brainstem location of hemorrhage (patients with cerebellar hemorrhage may be enrolled) - Serum creatinine > 1.4 mg/dl (123 μmol/L). Sites that currently perform CTA as standard of care for ICH will follow their standard procedures regarding renal insufficiency. - Known allergy to iodinated contrast media - Intravenous or intra-arterial administration of iodinated contrast media within the previous 24 hours of baseline CT scan - Known hereditary (e.g., hemophilia) or acquired hemorrhagic diathesis, coagulation factor deficiency, or anticoagulant therapy with INR > 1.2 - Known or suspected thrombocytopenia (unless current platelet count documented above 50,000 / μl) - Unfractionated heparin use with abnormal PTT - Low-molecular weight heparin use within the previous 24 hours - GPIIb/IIIa antagonist use in the previous two weeks - Glasgow Coma Scale score < 8 at time of proposed enrollment - Pre-admission modified Rankin Scale score > 2 - Baseline ICH volume of < 0.5 cc (Hematoma volume will be estimated by local investigators from the baseline CT using the ABC / 2 method.) - Baseline ICH volume of > 90 cc - Planned surgical evacuation of ICH within 24 hours of symptom onset (placement of intraventricular catheter is not a contraindication to study enrollment.) - Evidence of acute or subacute ischemic stroke on baseline qualifying CT scan - Clinical history of thromboembolism or ischemic vascular disease, including myocardial infarction, coronary artery bypass surgery, cardiac angina, transient ischemic attack, ischemic stroke, peripheral artery disease (vascular claudication), cerebral bypass surgery, carotid endarterectomy, deep venous thrombosis, pulmonary embolism, or coronary or cerebrovascular angioplasty or stenting. (Clinically silent evidence of old ischemia on EKG (Q waves) or CT scan (silent old infarct) will not be considered reasons for exclusion.) - Baseline electrocardiogram shows evidence of acute cardiac ischemia (ST elevation in two contiguous leads, new LBBB, or ST depression) - Clinical history suggestive of acute cardiac ischemia (e.g., chest pain) - Abnormal baseline troponin - Females of childbearing potential who are known to be pregnant and/or lactating or who have positive pregnancy tests on admission - Advanced or terminal illness or any other condition the investigator feels would pose a significant hazard to the patient if rFVIIa were administered - Recent (within 30 days) participation in any investigational drug or device trial or earlier participation in any investigational drug or device trial for which the duration of effect is expected to persist until the time of STOP-IT enrollment - Planned withdrawal of care or comfort care measures - Patient known or suspected of not being able to comply with trial protocol (e.g., due to alcoholism, drug dependency or psychological disorder) - Informed consent cannot be obtained from the patient or legally authorized representative

Additional Information

Official title The Spot Sign for Predicting and Treating Intracerebral Hemorrhage Growth Study
Principal investigator Matthew L. Flaherty, MD
Description Intracerebral hemorrhage (ICH)—breakage of a blood vessel with bleeding in the brain—is a devastating form of stroke with a 40-50 percent fatality rate and no proven treatment. Because the majority of deaths from ICH occur within several days of the stroke, interventions for improving outcomes must occur early in the treatment course. Among the potentially modifiable determinants of ICH outcome, hematoma growth is a particularly attractive target for intervention and a major focus of this trial. The purpose of this study is to determine if an imaging test called computed tomography angiography (CTA) can predict which individuals with ICH will experience significant growth in the size of the hemorrhage. Growth of the hemorrhage can cause additional injury and may worsen the outcome. For individuals who are at high risk for hemorrhage growth based on CTA results (i.e., a positive CTA "spot sign," evidence of contrast leakage within the hemorrhage), the study will compare the effects of a drug called recombinant activated factor VII (NovoSeven®) or rFVIIa with a placebo to determine which is better for reducing ICH growth. The primary goals of this trial are (1) to determine the sensitivity and specificity of the CTA spot sign for predicting hematoma growth; (2) to determine the feasibility of using CTA to identify individuals with ICH who are at high risk of hematoma growth and to select study participants for randomization to treatment with rFVIIa or placebo; and (3) to determine the rate of hematoma growth among spot-positive individuals at 24 hours—comparing individuals treated with rFVIIa to those treated with placebo. Approximately 184 persons with ICH will be enrolled in one of two study groups at 10 clinical sites across the United States and Canada. Participants with ICH who are determined by CTA to be at high risk for hemorrhage growth (CTA "spot sign" positive) will be randomized to receive either the active study medication, rFVIIa, at 80 mcg/kg, or to receive a placebo (an inactive substance). Participants with ICH who are determined by CTA not to be at high risk for hemorrhage growth (determined to be CTA "spot sign" negative) will be enrolled into a prospective observational group. Duration of the study for participants is approximately 3 months.
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by University of Cincinnati.