The Spot Sign for Predicting and Treating ICH Growth Study "STOP-IT"

Completed

Phase 2 Results N/A

Trial Description

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.

Detailed 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.

Conditions

Interventions

  • Recombinant Factor VIIa (NovoSeven)Drug
    Intervention Desc: Coagulation factor. Enhances local hemostasis when it binds to tissue factor
  • Placebo Drug
    Intervention Desc: An inactive substance (maximum dose volume 21.3 mL, equivalent to maximum weight of 160 kg)
    ARM 1: Kind: Experimental
    Label: 2
    Description: 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).
  • Recombinant activated factor VII Drug
    Intervention Desc: Participants will receive rFVIIa at 80 mcg/kg (maximum dose volume 21.3 mL, equivalent to maximum weight of 160 kg).
    ARM 1: Kind: Experimental
    Label: 1
    Description: 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 .

Trial Design

  • Allocation: Randomized
  • Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
  • Purpose: Treatment
  • Endpoint: Efficacy Study
  • Intervention: Parallel Assignment

Patient Involvement

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 but otherwise meeting the same criteria) will be enrolled into a prospective observational group. Participants will have a 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. Follow up will be done in 3 months.

Outcomes

Type Measure Time Frame Safety Issue
Primary Life-threatening thromboembolic complications defined as development of (1) acute myocardial ischemia; (2) acute cerebral ischemia; and (3) acute pulmonary embolism; 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; sensitivity and specificity of the spot sign for predicting hematoma growth.
Secondary Incidence of other potentially study drug related thromboembolic complications such as deep venous thrombosis and elevations in troponin not associated with ECG changes; 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; 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.
Primary Life-threatening thromboembolic complications defined as development of (1) acute myocardial ischemia; (2) acute cerebral ischemia; and (3) acute pulmonary embolism through day 4 after completion of study drug Yes
Primary 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. at 24 hours No
Primary The sensitivity and specificity of the spot sign for predicting hematoma growth 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. No
Secondary Incidence of other potentially study drug related thromboembolic complications such as deep venous thrombosis and elevations in troponin not associated with ECG changes through day 4 after completion of study drug Yes
Secondary 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 90 days (+/- 7 days) from time of study enrollment No
Secondary 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. 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. No
Secondary Rate of total hemorrhage volume growth (hematoma + IVH) among spot-positive subjects. 24 hours (+/- 3 hours) from baseline CT scan No
Primary 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. at 24 hours

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