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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
Sponsor:
Collaborator:
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Matthew Flaherty, University of Cincinnati

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Intracerebral Hemorrhage
Interventions Drug: recombinant activated factor VII
Drug: placebo
Enrollment 92
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Group 1 - Randomized to Study Drug Group 2 - Randomized to Placebo Group 3 - Observation Only Arm
Hide Arm/Group 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 .

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).

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)

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.
Period Title: Overall Study
Started 10 9 73
Completed 10 9 73
Not Completed 0 0 0
Arm/Group Title Group 1 - Randomized to Study Drug Group 2 - Randomized to Placebo Group 3 - Observation Only Arm Total
Hide Arm/Group 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 .

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).

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)

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. Total of all reporting groups
Overall Number of Baseline Participants 10 9 73 92
Hide Baseline Analysis Population Description
The baseline population consists of 19 subjects diagnosed as "Spot Positive" on CT and were eligible for randomization within the clinical trial portion of the protocol. In addition 73 subjects diagnosed as "Spot Negative" on CT were followed prospectively with no study intervention. All 92 subjects were followed to 90 days post stroke.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 10 participants 9 participants 73 participants 92 participants
65.4  (13.1) 62.4  (12.2) 60.7  (34.7) 61.3  (11.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 9 participants 73 participants 92 participants
Female
6
  60.0%
3
  33.3%
29
  39.7%
38
  41.3%
Male
4
  40.0%
6
  66.7%
44
  60.3%
54
  58.7%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 9 participants 73 participants 92 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
  10.0%
5
  55.6%
17
  23.3%
23
  25.0%
White
9
  90.0%
4
  44.4%
56
  76.7%
69
  75.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Canada Number Analyzed 10 participants 9 participants 73 participants 92 participants
3
  30.0%
1
  11.1%
23
  31.5%
27
  29.3%
United States Number Analyzed 10 participants 9 participants 73 participants 92 participants
7
  70.0%
8
  88.9%
50
  68.5%
65
  70.7%
Modified Rankin Score (mRS)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 9 participants 73 participants 92 participants
0
10
 100.0%
6
  66.7%
65
  89.0%
81
  88.0%
1
0
   0.0%
3
  33.3%
6
   8.2%
9
   9.8%
2
0
   0.0%
0
   0.0%
2
   2.7%
2
   2.2%
[1]
Measure Description: Measure of mobility prior to stroke (0=best, 5=worst)
Glasgow Coma Score/Scale (GCS)   [1] 
Median (Inter-Quartile Range)
Unit of measure:  Units on a scale
Number Analyzed 10 participants 9 participants 73 participants 92 participants
15
(14 to 15)
15
(14 to 15)
15
(14 to 15)
15
(14 to 15)
[1]
Measure Description: Scale to measure severity due to coma status (0=worst, 15=best)
National Institute of Health Stroke Scale (NIHSS) Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 10 participants 9 participants 73 participants 92 participants
14.1  (3.9) 12.1  (4.9) 10.3  (6.2) 10.9  (6.0)
[1]
Measure Description: The National Institute of Health Stroke Scale (NIHSS) Score is a scale which measures stroke severity (0=best, 42=worst)
Time from Stroke to Computed Tomography (CT) Scan  
Mean (Standard Deviation)
Unit of measure:  Minutes
Number Analyzed 10 participants 9 participants 73 participants 92 participants
158.8  (77.0) 90.2  (49.9) 159.8  (81.9) 152.9  (80.9)
Time from Stroke to Study Drug Administration   [1] 
Mean (Standard Deviation)
Unit of measure:  Minutes
Number Analyzed 10 participants 9 participants 0 participants 19 participants
269.9  (68.3) 181.1  (47.1) 222.5  (70.4)
[1]
Measure Analysis Population Description: The Observational group did not receive study drug so the variable "Time from stroke to study drug administration" is not applicable
1.Primary Outcome
Title Number of Study Subjects With Life-threatening Thromboembolic Complications
Hide Description Thromboembolic complications are defined as development of (1) acute myocardial ischemia; or (2) acute cerebral ischemia; or (3) acute pulmonary embolism
Time Frame through day 4 after completion of study drug administration
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis population consists of 19 subjects diagnosed as "Spot Positive" on CT who were eligible for randomization within the clinical trial portion of the protocol, as well as 73 subjects diagnosed as "Spot Negative" on CT who were followed prospectively with no study intervention. Statistical comparison involves only Group1 and Group 2.
Arm/Group Title Group 1 - Randomized to Study Drug Group 2 - Randomized to Placebo Group 3 - Observation Only Arm
Hide Arm/Group 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 .

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).

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)

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.
Overall Number of Participants Analyzed 10 9 73
Measure Type: Count of Participants
Unit of Measure: Participants
1
  10.0%
0
   0.0%
0
   0.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1 - Randomized to Study Drug, Group 2 - Randomized to Placebo
Comments Fisher's exact test
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.00
Comments not adjusted for multiple comparisons as a prior hypothesis critical value <0.05
Method Fisher Exact
Comments [Not Specified]
2.Primary Outcome
Title Number of Subjects With Hematoma Growth Among Spot Sign Positive Subjects at 24 Hours.
Hide Description 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.
Time Frame From baseline to 24 hours
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis population consists of 19 subjects diagnosed as "Spot Positive" on CT who were eligible for randomization within the clinical trial portion of the protocol, as well as 73 subjects diagnosed as "Spot Negative" on CT who were followed prospectively with no study intervention. Statistical comparison involves only Group1 and Group 2.
Arm/Group Title Group 1 - Randomized to Study Drug Group 2 - Randomized to Placebo Group 3 - Observation Only Arm
Hide Arm/Group 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 .

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).

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)

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.
Overall Number of Participants Analyzed 10 9 73
Measure Type: Count of Participants
Unit of Measure: Participants
4
  40.0%
5
  55.6%
8
  11.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1 - Randomized to Study Drug, Group 2 - Randomized to Placebo
Comments Only the randomized subjects will be compared
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.66
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
3.Primary Outcome
Title The Sensitivity of the Spot Sign for Predicting Hematoma Growth
Hide Description 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
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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis population consists of 19 subjects diagnosed as "Spot Positive" on CT who were eligible for randomization within the clinical trial portion of the protocol, as well as 73 subjects diagnosed as "Spot Negative" on CT who were followed prospectively with no study intervention. Statistical comparison involves only Group 2 and Group 3.
Arm/Group Title Group 1 - Randomized to Study Drug Group 2 - Randomized to Placebo Group 3 - Observation Only Arm
Hide Arm/Group 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 .

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).

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)

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.
Overall Number of Participants Analyzed 10 9 73
Measure Type: Count of Participants
Unit of Measure: Participants
4
  40.0%
5
  55.6%
8
  11.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 2 - Randomized to Placebo, Group 3 - Observation Only Arm
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Sensitivity
Estimated Value 38.5
Confidence Interval (2-Sided) 95%
17.6 to 64.6
Estimation Comments [Not Specified]
4.Primary Outcome
Title The Specificity of the Spot Sign for Predicting Hematoma Growth
Hide Description 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.
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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis population consists of 19 subjects diagnosed as "Spot Positive" on CT who were eligible for randomization within the clinical trial portion of the protocol, as well as 73 subjects diagnosed as "Spot Negative" on CT who were followed prospectively with no study intervention. Statistical comparison involves only Group 2 and Group 3.
Arm/Group Title Group 1 - Randomized to Study Drug Group 2 - Randomized to Placebo Group 3 - Observation Only Arm
Hide Arm/Group 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 .

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).

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)

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.
Overall Number of Participants Analyzed 10 9 73
Measure Type: Count of Participants
Unit of Measure: Participants
4
  40.0%
5
  55.6%
8
  11.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 2 - Randomized to Placebo, Group 3 - Observation Only Arm
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Specificity
Estimated Value 94.2
Confidence Interval (2-Sided) 95%
85.6 to 98.1
Estimation Comments [Not Specified]
5.Secondary Outcome
Title 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
Hide Description 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
Time Frame through day 4 after completion of study drug
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis population consists of 19 subjects diagnosed as "Spot Positive" on CT who were eligible for randomization within the clinical trial portion of the protocol, as well as 73 subjects diagnosed as "Spot Negative" on CT who were followed prospectively with no study intervention. Statistical comparison involves only Group1 and Group 2.
Arm/Group Title Group 1 - Randomized to Study Drug Group 2 - Randomized to Placebo Group 3 - Observation Only Arm
Hide Arm/Group 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 .

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).

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)

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.
Overall Number of Participants Analyzed 10 9 73
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
1
  11.1%
4
   5.5%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1 - Randomized to Study Drug, Group 2 - Randomized to Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.47
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
6.Secondary Outcome
Title Number of Spot Positive Subjects With 90-day Outcome of Modified Rankin Scale Score >= 5
Hide Description 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.
Time Frame 90 days (+/- 7 days) from time of study enrollment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis population consists of 19 subjects diagnosed as "Spot Positive" on CT who were eligible for randomization within the clinical trial portion of the protocol, as well as 73 subjects diagnosed as "Spot Negative" on CT who were followed prospectively with no study intervention. Statistical comparison involves only Group1 and Group 2.
Arm/Group Title Group 1 - Randomized to Study Drug Group 2 - Randomized to Placebo Group 3 - Observation Only Arm
Hide Arm/Group 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 .

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).

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)

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.
Overall Number of Participants Analyzed 10 9 73
Measure Type: Count of Participants
Unit of Measure: Participants
3
  30.0%
1
  11.1%
6
   8.2%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1 - Randomized to Study Drug, Group 2 - Randomized to Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.58
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
7.Secondary Outcome
Title 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
Hide Description 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.
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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis population consists of 19 subjects diagnosed as "Spot Positive" on CT who were eligible for randomization within the clinical trial portion of the protocol, as well as 73 subjects diagnosed as "Spot Negative" on CT who were followed prospectively with no study intervention. Overall agreement was assessed but reported by group below.
Arm/Group Title Group 1 - Randomized to Study Drug Group 2 - Randomized to Placebo Group 3 - Observation Only Arm
Hide Arm/Group 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 .

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).

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)

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.
Overall Number of Participants Analyzed 10 9 73
Measure Type: Count of Participants
Unit of Measure: Participants
10
 100.0%
6
  66.7%
69
  94.5%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1 - Randomized to Study Drug, Group 2 - Randomized to Placebo, Group 3 - Observation Only Arm
Comments [Not Specified]
Type of Statistical Test Other
Comments A Kappa test of overall agreement was used
Method of Estimation Estimation Parameter Kappa
Estimated Value 0.77
Confidence Interval (2-Sided) 95%
0.61 to 0.93
Estimation Comments A kappa of >0.75 is considered excellent agreement
8.Secondary Outcome
Title Percent Change in Total Hemorrhage Volume (Intracerebral Hemorrhage (ICH) Plus Intraventricular Hemorrhage (IVH)).
Hide Description 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.
Time Frame 24 hours (+/- 3 hours) from baseline CT scan
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis population consists of 19 subjects diagnosed as "Spot Positive" on CT who were eligible for randomization within the clinical trial portion of the protocol, as well as 73 subjects diagnosed as "Spot Negative" on CT who were followed prospectively with no study intervention. Statistical comparison involves only Group1 and Group 2.
Arm/Group Title Group 1 - Randomized to Study Drug Group 2 - Randomized to Placebo Group 3 - Observation Only Arm
Hide Arm/Group 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 .

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).

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)

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.
Overall Number of Participants Analyzed 10 9 73
Median (Inter-Quartile Range)
Unit of Measure: Percent change from baseline to 24 hours
13.51
(-0.84 to 33.08)
20.96
(14.07 to 96.57)
5.12
(0.28 to 16.64)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1 - Randomized to Study Drug, Group 2 - Randomized to Placebo
Comments Groups 1 and 2 only the spot positive subjects randomized to interventional drug or placebo
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.25
Comments [Not Specified]
Method Kruskal-Wallis
Comments [Not Specified]
Time Frame Adverse events were collected out to 90 days from stroke onset
Adverse Event Reporting Description

Adverse events and serious adverse events were defined as per clinicaltrials.gov

A case report form (CRF) was used to collect:

1. Presence, description and type of adverse events; 2. Severity (mild, moderate, severe, life-threatening, death); 3. Serious (yes, no); 4. Expected (yes, no); 5. Date/Time of onset; 6. Outcome (resolved, continuing, death); 7. Date of resolution; 8. Relation to disease; 9. Relationship to study project; 10. Action taken

 
Arm/Group Title Group 1 - Randomized to Study Drug Group 2 - Randomized to Placebo Group 3 - Observation Only Arm
Hide Arm/Group 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 .

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).

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)

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.
All-Cause Mortality
Group 1 - Randomized to Study Drug Group 2 - Randomized to Placebo Group 3 - Observation Only Arm
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/10 (20.00%)      0/9 (0.00%)      4/73 (5.48%)    
Show Serious Adverse Events Hide Serious Adverse Events
Group 1 - Randomized to Study Drug Group 2 - Randomized to Placebo Group 3 - Observation Only Arm
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/10 (40.00%)      4/9 (44.44%)      16/73 (21.92%)    
Cardiac disorders       
New onset Afib  1  0/10 (0.00%)  0 0/9 (0.00%)  0 1/73 (1.37%)  1
Congenital, familial and genetic disorders       
Atreriovenous malformation (AVM)  1 [1]  0/10 (0.00%)  0 0/9 (0.00%)  0 3/73 (4.11%)  3
Gastrointestinal disorders       
Oropharyngeal disorder  1  0/10 (0.00%)  0 0/9 (0.00%)  0 1/73 (1.37%)  1
Infections and infestations       
Ventilator aquired pneuminia  1  0/10 (0.00%)  0 0/9 (0.00%)  0 1/73 (1.37%)  1
Gram negative bacteremia  1  1/10 (10.00%)  1 0/9 (0.00%)  0 0/73 (0.00%)  0
Injury, poisoning and procedural complications       
RESPIRATORY DISTRESS SECONDARY TO TRACH OBSTRUCTION  1  1/10 (10.00%)  1 0/9 (0.00%)  0 0/73 (0.00%)  0
Left acute on chronic subdural hematoma  1 [2]  0/10 (0.00%)  0 0/9 (0.00%)  0 1/73 (1.37%)  1
Investigations       
Elevated Troponin  1  1/10 (10.00%)  1 0/9 (0.00%)  0 0/73 (0.00%)  0
Metabolism and nutrition disorders       
Hyperglycemia  1  0/10 (0.00%)  0 0/9 (0.00%)  0 1/73 (1.37%)  1
Musculoskeletal and connective tissue disorders       
Weakness left leg  1  0/10 (0.00%)  0 1/9 (11.11%)  1 0/73 (0.00%)  0
Nervous system disorders       
Cerebral Edema  1  1/10 (10.00%)  1 1/9 (11.11%)  1 2/73 (2.74%)  2
Seizure  1 [3]  1/10 (10.00%)  1 2/9 (22.22%)  2 2/73 (2.74%)  2
Slurred speech  1  0/10 (0.00%)  0 1/9 (11.11%)  1 0/73 (0.00%)  0
Increasing mass effect  1  1/10 (10.00%)  1 0/9 (0.00%)  0 0/73 (0.00%)  0
POSSIBLE MCA VESSEL THROMBOSIS WITHOUT ISCHEMIC STROKE  1  1/10 (10.00%)  1 0/9 (0.00%)  0 0/73 (0.00%)  0
Significant expansion of ICH  1 [4]  1/10 (10.00%)  1 0/9 (0.00%)  0 1/73 (1.37%)  1
Cortical vein thrombosis  1  0/10 (0.00%)  0 0/9 (0.00%)  0 1/73 (1.37%)  1
Neurologic deterioration  1  0/10 (0.00%)  0 0/9 (0.00%)  0 3/73 (4.11%)  3
Neuroleptic malignant syndrome  1  0/10 (0.00%)  0 0/9 (0.00%)  0 1/73 (1.37%)  1
Subarachnoid hemorrhage  1  0/10 (0.00%)  0 0/9 (0.00%)  0 1/73 (1.37%)  1
WORSENING PERIHEMATOMAL EDEMA AND INCREASING MIDLINE SHIFT  1  0/10 (0.00%)  0 0/9 (0.00%)  0 1/73 (1.37%)  2
Psychiatric disorders       
Mental status changes  1 [5]  0/10 (0.00%)  0 0/9 (0.00%)  0 2/73 (2.74%)  2
Renal and urinary disorders       
Acute exacerbation of renal failure  1  1/10 (10.00%)  1 0/9 (0.00%)  0 0/73 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
O2 desats on ventilator  1  1/10 (10.00%)  1 0/9 (0.00%)  0 0/73 (0.00%)  0
Pulmonary embolism  1  1/10 (10.00%)  1 0/9 (0.00%)  0 3/73 (4.11%)  3
Respiratory distress  1  2/10 (20.00%)  4 0/9 (0.00%)  0 0/73 (0.00%)  0
Respiratory failure  1  0/10 (0.00%)  0 0/9 (0.00%)  0 1/73 (1.37%)  1
Vascular disorders       
Deep vein thrombosis (DVT)  1 [6]  1/10 (10.00%)  1 0/9 (0.00%)  0 2/73 (2.74%)  2
Hemorrhage expansion  1  1/10 (10.00%)  1 0/9 (0.00%)  0 1/73 (1.37%)  1
Malignant hypertension  1  1/10 (10.00%)  1 0/9 (0.00%)  0 0/73 (0.00%)  0
Hypertensive urgency  1  0/10 (0.00%)  0 0/9 (0.00%)  0 1/73 (1.37%)  1
PE  1  0/10 (0.00%)  0 0/9 (0.00%)  0 1/73 (1.37%)  1
1
Term from vocabulary, MedDRA (19.0)
Indicates events were collected by systematic assessment
[1]
One not seen on baseline imaging, one complex
[2]
the term was taken directly from the adverse event CRF
[3]
Includes "seizure activity" in Group 1 and "possible simple partial seizure" in Group 3
[4]
includes "EXACERBATION OF INTRACEREBRAL HEMORRHAGE" in Group 1
[5]
Includes "DEPRESSED MENTAL STATUS SECONDARY TO ICH/IVH"
[6]
including one "right iliofemoral DVT"
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Group 1 - Randomized to Study Drug Group 2 - Randomized to Placebo Group 3 - Observation Only Arm
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   9/10 (90.00%)      8/9 (88.89%)      65/73 (89.04%)    
Blood and lymphatic system disorders       
Leukocytosis  1  2/10 (20.00%)  2 1/9 (11.11%)  1 2/73 (2.74%)  2
Leukopenia  1  1/10 (10.00%)  1 0/9 (0.00%)  0 0/73 (0.00%)  0
Anemia  1  0/10 (0.00%)  0 0/9 (0.00%)  0 7/73 (9.59%)  7
Cardiac disorders       
Bradycardia  1  2/10 (20.00%)  2 0/9 (0.00%)  0 1/73 (1.37%)  1
Congestive heart failure  1 [1]  1/10 (10.00%)  1 1/9 (11.11%)  1 0/73 (0.00%)  0
Tachycardia  1  1/10 (10.00%)  1 0/9 (0.00%)  0 3/73 (4.11%)  3
Endocrine disorders       
SIADH  1  0/10 (0.00%)  0 1/9 (11.11%)  1 0/73 (0.00%)  0
Gastrointestinal disorders       
Constipation  1  6/10 (60.00%)  6 2/9 (22.22%)  2 10/73 (13.70%)  10
Diarrhea  1  1/10 (10.00%)  1 0/9 (0.00%)  0 4/73 (5.48%)  4
Distended abdomen  1  1/10 (10.00%)  1 0/9 (0.00%)  0 0/73 (0.00%)  0
Dysphagia  1  2/10 (20.00%)  2 1/9 (11.11%)  1 3/73 (4.11%)  3
Nausea  1  3/10 (30.00%)  3 1/9 (11.11%)  1 14/73 (19.18%)  14
Rectal pain  1 [2]  1/10 (10.00%)  2 0/9 (0.00%)  0 0/73 (0.00%)  0
Vomiting  1  0/10 (0.00%)  0 0/9 (0.00%)  0 4/73 (5.48%)  4
General disorders       
Chest pain  1  1/10 (10.00%)  1 1/9 (11.11%)  1 2/73 (2.74%)  2
Fever  1  3/10 (30.00%)  3 3/9 (33.33%)  4 6/73 (8.22%)  6
Generalized pain  1  1/10 (10.00%)  1 1/9 (11.11%)  1 7/73 (9.59%)  7
Pain with catherization  1  1/10 (10.00%)  1 0/9 (0.00%)  0 0/73 (0.00%)  0
Right hand PIV infultration  1  1/10 (10.00%)  1 0/9 (0.00%)  0 0/73 (0.00%)  0
Shivering  1  0/10 (0.00%)  0 1/9 (11.11%)  1 0/73 (0.00%)  0
Infections and infestations       
Candidiasis  1 [3]  1/10 (10.00%)  1 1/9 (11.11%)  1 0/73 (0.00%)  0
Tracheitis  1  1/10 (10.00%)  1 0/9 (0.00%)  0 0/73 (0.00%)  0
Urinary tract infection  1  5/10 (50.00%)  5 1/9 (11.11%)  1 12/73 (16.44%)  13
Ventriculitis  1  0/10 (0.00%)  0 1/9 (11.11%)  1 0/73 (0.00%)  0
Pneumonia  1  0/10 (0.00%)  0 0/9 (0.00%)  0 4/73 (5.48%)  4
Injury, poisoning and procedural complications       
Bruising on forearms  1 [4]  1/10 (10.00%)  1 0/9 (0.00%)  0 1/73 (1.37%)  1
Fall from bed  1  2/10 (20.00%)  2 0/9 (0.00%)  0 0/73 (0.00%)  0
Investigations       
ELEVATED ERYTHROCYTE SEDIMENTATION RATE  1  1/10 (10.00%)  1 0/9 (0.00%)  0 0/73 (0.00%)  0
Elevated troponin  1  1/10 (10.00%)  1 2/9 (22.22%)  2 5/73 (6.85%)  5
Prolonged prothrombin time  1  1/10 (10.00%)  1 0/9 (0.00%)  0 0/73 (0.00%)  0
T wave inversion  1  0/10 (0.00%)  0 1/9 (11.11%)  1 0/73 (0.00%)  0
Metabolism and nutrition disorders       
Hyperglycemia  1  1/10 (10.00%)  1 4/9 (44.44%)  4 13/73 (17.81%)  13
Hypocalcemia  1  1/10 (10.00%)  1 0/9 (0.00%)  0 0/73 (0.00%)  0
Hypokalemia  1  3/10 (30.00%)  3 2/9 (22.22%)  2 17/73 (23.29%)  17
Hyponatremia  1  2/10 (20.00%)  2 1/9 (11.11%)  1 0/73 (0.00%)  0
Hypernatremia  1  0/10 (0.00%)  0 1/9 (11.11%)  1 3/73 (4.11%)  3
Hypomagnesemia  1  0/10 (0.00%)  0 3/9 (33.33%)  3 3/73 (4.11%)  3
hypophosphatemia  1  0/10 (0.00%)  0 1/9 (11.11%)  2 3/73 (4.11%)  3
Metabolic acidosis  1  0/10 (0.00%)  0 1/9 (11.11%)  1 0/73 (0.00%)  0
Hyperlipidemia  1  0/10 (0.00%)  0 0/9 (0.00%)  0 4/73 (5.48%)  4
Musculoskeletal and connective tissue disorders       
Back pain  1  2/10 (20.00%)  2 0/9 (0.00%)  0 4/73 (5.48%)  4
Leg pain  1 [5]  1/10 (10.00%)  1 1/9 (11.11%)  1 1/73 (1.37%)  2
Right shoulder rotator cuff tear  1  1/10 (10.00%)  1 0/9 (0.00%)  0 0/73 (0.00%)  0
Nervous system disorders       
Aneurysm  1 [6]  1/10 (10.00%)  2 0/9 (0.00%)  0 0/73 (0.00%)  0
Headache  1  5/10 (50.00%)  6 4/9 (44.44%)  4 11/73 (15.07%)  11
Somulence  1 [7]  1/10 (10.00%)  1 1/9 (11.11%)  1 0/73 (0.00%)  0
Asymptomatic MRI DWI lesion  1  0/10 (0.00%)  0 1/9 (11.11%)  1 0/73 (0.00%)  0
Cerebral edema / hydrocephalus  1  0/10 (0.00%)  0 3/9 (33.33%)  3 1/73 (1.37%)  1
Confused speech  1  0/10 (0.00%)  0 1/9 (11.11%)  1 0/73 (0.00%)  0
Difficult to arouse  1  0/10 (0.00%)  0 1/9 (11.11%)  1 0/73 (0.00%)  0
Dizziness  1  0/10 (0.00%)  0 1/9 (11.11%)  1 0/73 (0.00%)  0
Peripheral neuropathy  1  0/10 (0.00%)  0 1/9 (11.11%)  1 0/73 (0.00%)  0
Seizure  1 [8]  0/10 (0.00%)  0 1/9 (11.11%)  1 2/73 (2.74%)  3
Psychiatric disorders       
Anxiety  1  1/10 (10.00%)  1 0/9 (0.00%)  0 2/73 (2.74%)  2
Confusion  1  1/10 (10.00%)  1 0/9 (0.00%)  0 0/73 (0.00%)  0
Depression  1  3/10 (30.00%)  3 1/9 (11.11%)  1 5/73 (6.85%)  5
Agitation  1  0/10 (0.00%)  0 2/9 (22.22%)  2 7/73 (9.59%)  8
Alcohol withdrawal  1  0/10 (0.00%)  0 1/9 (11.11%)  1 0/73 (0.00%)  0
Insomnia  1 [9]  0/10 (0.00%)  0 1/9 (11.11%)  1 3/73 (4.11%)  3
Altered mental status  1 [10]  0/10 (0.00%)  0 1/9 (11.11%)  1 1/73 (1.37%)  1
Renal and urinary disorders       
Renal failure  1 [11]  1/10 (10.00%)  1 0/9 (0.00%)  0 0/73 (0.00%)  0
Hematuria  1  1/10 (10.00%)  1 0/9 (0.00%)  0 0/73 (0.00%)  0
Urinary retension  1  3/10 (30.00%)  3 0/9 (0.00%)  0 4/73 (5.48%)  4
Respiratory, thoracic and mediastinal disorders       
Cough  1  1/10 (10.00%)  1 0/9 (0.00%)  0 0/73 (0.00%)  0
Nasal congestion  1  1/10 (10.00%)  1 0/9 (0.00%)  0 0/73 (0.00%)  0
Pleural effusion  1 [12]  1/10 (10.00%)  2 1/9 (11.11%)  2 1/73 (1.37%)  1
Pulmonary hypertension  1  0/10 (0.00%)  0 1/9 (11.11%)  1 0/73 (0.00%)  0
Skin and subcutaneous tissue disorders       
Skin breakdown / irritation  1  0/10 (0.00%)  0 2/9 (22.22%)  2 3/73 (4.11%)  3
Vascular disorders       
Hypertension  1  5/10 (50.00%)  5 4/9 (44.44%)  4 32/73 (43.84%)  32
Hypotension  1  1/10 (10.00%)  1 0/9 (0.00%)  0 2/73 (2.74%)  2
1
Term from vocabulary, MedDRA (19.0)
Indicates events were collected by systematic assessment
[1]
Mild in group 1
[2]
Group 1 due to hemorrhoids
[3]
Group1 - oral
[4]
Group 1- on forearms Group 3 - on thigh
[5]
Group 1 right leg Group 2 right knee Group 3 "right knee arthralgia/effusion"
[6]
Group 1 "SMALL SACCULAR ANEURYSM BASILAR ARTERY" and "ANEURYSM LEFT INTERNAL CAROID ARTERY" same subject
[7]
Group1 - increasing Group 2 - persistence
[8]
Group 3 - one subject "seizure post (after) arteriovenous malformation repair" Group 3 - one subject "SIMPLE PARTIAL SEIZURES" and "EXACERBATION OF SIMPLE PARTIAL SEIZURE"
[9]
Group 2 - intermittent
[10]
Group 2 -worsening
[11]
Group1 - exacerbation in one subject
[12]
Group1 - "PLEURAL EFFUSION, ATELECTASIS" Group 2 "SMALL BILATERAL PLEURAL EFFUSIONS"
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Dr Jane Khoury, Professor of Pediatrics
Organization: Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center
Phone: 513-636-2690
Responsible Party: Matthew Flaherty, University of Cincinnati
ClinicalTrials.gov Identifier: NCT00810888     History of Changes
Other Study ID Numbers: P50NS044283_STOP_IT
2P50NS044283 ( U.S. NIH Grant/Contract )
First Submitted: December 15, 2008
First Posted: December 18, 2008
Results First Submitted: September 22, 2017
Results First Posted: January 8, 2018
Last Update Posted: March 16, 2018