The Spot Sign for Predicting and Treating ICH Growth Study (STOP-IT)
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|ClinicalTrials.gov Identifier: NCT00810888|
Recruitment Status : Completed
First Posted : December 18, 2008
Results First Posted : January 8, 2018
Last Update Posted : March 16, 2018
|Condition or disease||Intervention/treatment||Phase|
|Intracerebral Hemorrhage||Drug: recombinant activated factor VII Drug: placebo||Phase 2|
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 12 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||92 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||The Spot Sign for Predicting and Treating Intracerebral Hemorrhage Growth Study|
|Study Start Date :||November 2010|
|Actual Primary Completion Date :||April 2016|
|Actual Study Completion Date :||April 2016|
Active Comparator: Group 1-Recombinant activated factor VII
Participants with ICH determined by CTA to be high risk for hemorrhage growth ("spot sign" positive for contrast leakage within the brain hematoma) randomized to receive rFVIIa at 80 mcg/kg (max dose 21.3 mL).
Drug: 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: Group 2 - Placebo
Participants with ICH determined by CTA to be high risk for hemorrhage growth ("spot sign" positive for contrast leakage within the brain hematoma) will be randomized to receive placebo.
An inactive substance (maximum dose volume 21.3 mL, equivalent to maximum weight of 160 kg)
No Intervention: Group 3 - Observation Only Arm
Participants with ICHdetermined by CTA not to be at high risk for hemorrhage growth (CTA "spot sign" negative) enrolled into a prospective observational group.
- Number of Study Subjects With Life-threatening Thromboembolic Complications [ Time Frame: through day 4 after completion of study drug administration ]Thromboembolic complications are defined as development of (1) acute myocardial ischemia; or (2) acute cerebral ischemia; or (3) acute pulmonary embolism
- Number of Subjects With Hematoma Growth Among Spot Sign Positive Subjects at 24 Hours. [ Time Frame: From baseline to 24 hours ]Comparison of only the subjects with a positive spot sign with respect to a categorical measure of hematoma growth from baseline to 24 hours. the outcome of interest is the percent of subjects with hematoma growth > 33% or > 6 cc increase in volume, from baseline to 24 hours.
- The Sensitivity of the Spot Sign for Predicting Hematoma Growth [ Time Frame: Baseline head CT scan within 5 hours of stroke, followed by a CT angiogram. Hematoma growth determined by comparison with a head CT scan performed at 24 hours. ]The outcome measure is hematoma growth. Groups 2 and 3 only will be compared as Group 1 had administration of study drug which was hypothesized to reduce hematoma growth. Sensitivity was estimated. Sensitivity or true positive rate is defined as, the number of strokes correctly identified as spot positive according to the "gold standard" / the total number of strokes identified as spot positive
- The Specificity of the Spot Sign for Predicting Hematoma Growth [ Time Frame: Baseline head CT scan within 5 hours of stroke, followed by a CT angiogram. Hematoma growth determined by comparison with a head CT scan performed at 24 hours. ]The outcome measure is hematoma growth. Groups 2 and 3 only will be compared as group 1 had administration of study drug which was hypothesized to reduce hematoma growth. Specificity was estimated. Specificity or true negative rate is defined as, the number of non-spot positive (spot negative) strokes according to the "gold standard" / the total number of strokes identified as not spot positive.
- Number of Participants With Other Potentially Study Drug Related Thromboembolic Complications Such as Deep Venous Thrombosis (DVT) and Elevations in Troponin Not Associated With ECG Changes [ Time Frame: through day 4 after completion of study drug ]Evidence of a deep venous thrombosis or an elevation of troponin within 4 days of completion of study drug administration that are not associated with ECG changes that could be related to the study drug
- Number of Spot Positive Subjects With 90-day Outcome of Modified Rankin Scale Score >= 5 [ Time Frame: 90 days (+/- 7 days) from time of study enrollment ]The modified Rankin Scale (0 is best, 5 is worst - non dead, 6 is dead) was used to define a bad outcome; categorized as a score >=5 versus <5. As the aim of the study was to examine the effect of rFIV!!a only the randomized groups, 1 and 2, defined as spot positive by CTA were compared.
- Number of Participants With Agreement Between the Clinical Site Radiologists and the Study Radiologist With Respect to Identification of a Positive Spot Sign or the Absence of Positive Spot Sign on CTA [ 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. ]The CTA was originally interpreted by the site radiologist so that subjects could be identified as having a positive spot sign for eligibility for randomization. The positive spot sign is indicative that there is potential for further hemorrhagic growth and these subjects were thus eligible to be randomized to receive investigational drug or placebo. The CTA scans were subsequently assessed by the study radiologist and compared for agreement.
- Percent Change in Total Hemorrhage Volume (Intracerebral Hemorrhage (ICH) Plus Intraventricular Hemorrhage (IVH)). [ Time Frame: 24 hours (+/- 3 hours) from baseline CT scan ]Percent change in total volume (intracerebral hemorrhage (ICH) plus intraventricular hemorrhage (IVH)) from baseline CT to 24 hour CT. Percent change is expressed as difference between 24 hour total volume and baseline total volume divided by baseline total volume, expressed as a percentage. In order to examine the effect of rFIVIIa, the randomized groups, Group 1 and Group 2 only were statistically compared.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00810888
|United States, Arizona|
|St. Joseph's Hospital and Medical Center|
|Phoenix, Arizona, United States, 85013|
|United States, California|
|University of California, San Diego|
|San Diego, California, United States, 92103|
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|United States, Missouri|
|Saint Louis, Missouri, United States, 63110|
|United States, Ohio|
|University of Cincinnati—Clinical Coordinating Center|
|Cincinnati, Ohio, United States, 45267-0525|
|United States, Pennsylvania|
|University of Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19104-4283|
|University of Pittsburgh Medical Center|
|Pittsburgh, Pennsylvania, United States, 15213|
|United States, South Carolina|
|Medical University of South Carolina|
|Charleston, South Carolina, United States, 29425|
|University of Calgary|
|Calgary, Alberta, Canada, T2N2T9|
|Sunnybrook Health Science Center|
|Toronto, Ontario, Canada, M4N3M5|
|Principal Investigator:||Matthew L. Flaherty, MD||University of Cincinnati|
|Principal Investigator:||Edward C. Jauch, MD, MS||Primary Emergency Medicine Investigator, Medical University of South Carolina|