Trial Outcomes & Findings for Minimally Invasive Surgery Plus Rt-PA for ICH Evacuation Phase III (NCT NCT01827046)
NCT ID: NCT01827046
Last Updated: 2019-09-27
Results Overview
Dichotomized, adjudicated, cross-sectional modified Rankin Scale (mRS) score 0-3 vs. 4-6 at 365 days post-ictus, adjusting for baseline (pre-randomization) variables used in covariate adaptive randomization as well as the clinically established severity variables IVH size and ICH location (lobar or deep). Ictus refers to symptom onset. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from: 0=No symptoms at all, 1=No significant disability, 2=Slight disability, 3=Moderate disability, 4=Moderately severe disability, 5=Severe disability and 6=death. Dichotomized scores are: 0-3=No symptoms to moderate disability requiring some assistance; 4-6=Moderately severe disability requiring complete assistance to death.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
499 participants
Primary outcome timeframe
Day 365
Results posted on
2019-09-27
Participant Flow
Recruitment and randomization occurred at 78 hospitals in USA, Canada, Europe, Australia, and Asia
Participant milestones
| Measure |
MIS Plus Rt-PA Management
Subjects randomized to the Minimally Invasive Surgery (MIS) plus recombinant tissue plasminogen activator (rt-PA) management arm will undergo minimally invasive surgery followed by up to 9 doses of 1.0 mg of rt-PA (Activase/Alteplase/CathFlo) for intracerebral hemorrhage clot resolution.
rt-PA: Up to 9 doses of 1.0 mg of rt-PA will be administered through the catheter that was placed directly into the intracerebral hemorrhage using minimally invasive surgery.
|
Medical Management
Subjects randomized to medical management will receive the standard medical therapies for the treatment of intracerebral hemorrhage, which includes ICU care only and no planned surgical intervention.
|
|---|---|---|
|
Overall Study
STARTED
|
250
|
249
|
|
Overall Study
COMPLETED
|
249
|
240
|
|
Overall Study
NOT COMPLETED
|
1
|
9
|
Reasons for withdrawal
| Measure |
MIS Plus Rt-PA Management
Subjects randomized to the Minimally Invasive Surgery (MIS) plus recombinant tissue plasminogen activator (rt-PA) management arm will undergo minimally invasive surgery followed by up to 9 doses of 1.0 mg of rt-PA (Activase/Alteplase/CathFlo) for intracerebral hemorrhage clot resolution.
rt-PA: Up to 9 doses of 1.0 mg of rt-PA will be administered through the catheter that was placed directly into the intracerebral hemorrhage using minimally invasive surgery.
|
Medical Management
Subjects randomized to medical management will receive the standard medical therapies for the treatment of intracerebral hemorrhage, which includes ICU care only and no planned surgical intervention.
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
1
|
5
|
|
Overall Study
Withdrawal by Subject
|
0
|
4
|
Baseline Characteristics
Minimally Invasive Surgery Plus Rt-PA for ICH Evacuation Phase III
Baseline characteristics by cohort
| Measure |
MIS Plus Rt-PA Management
n=250 Participants
Subjects randomized to the MIS plus rt-PA management arm will undergo minimally invasive surgery followed by up to 9 doses of 1.0 mg of rt-PA (Activase/Alteplase/CathFlo) for intracerebral hemorrhage clot resolution.
rt-PA: Up to 9 doses of 1.0 mg of rt-PA will be administered through the catheter that was placed directly into the intracerebral hemorrhage using minimally invasive surgery.
|
Medical Management
n=249 Participants
Subjects randomized to medical management will receive the standard medical therapies for the treatment of intracerebral hemorrhage, which includes ICU care only and no planned surgical intervention.
|
Total
n=499 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
62 years
n=5 Participants
|
62 years
n=7 Participants
|
62 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
91 Participants
n=5 Participants
|
103 Participants
n=7 Participants
|
194 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
159 Participants
n=5 Participants
|
146 Participants
n=7 Participants
|
305 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
34 Participants
n=5 Participants
|
34 Participants
n=7 Participants
|
68 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
216 Participants
n=5 Participants
|
215 Participants
n=7 Participants
|
431 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
12 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
30 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
46 Participants
n=5 Participants
|
41 Participants
n=7 Participants
|
87 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
190 Participants
n=5 Participants
|
184 Participants
n=7 Participants
|
374 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
Australia
|
2 participants
n=5 Participants
|
2 participants
n=7 Participants
|
4 participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
3 participants
n=5 Participants
|
4 participants
n=7 Participants
|
7 participants
n=5 Participants
|
|
Region of Enrollment
China
|
5 participants
n=5 Participants
|
5 participants
n=7 Participants
|
10 participants
n=5 Participants
|
|
Region of Enrollment
Europe
|
41 participants
n=5 Participants
|
44 participants
n=7 Participants
|
85 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
199 participants
n=5 Participants
|
194 participants
n=7 Participants
|
393 participants
n=5 Participants
|
|
Tobacco use
|
50 Participants
n=5 Participants
|
39 Participants
n=7 Participants
|
89 Participants
n=5 Participants
|
|
Cocaine use
|
11 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
On anticoagulants
|
24 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
34 Participants
n=5 Participants
|
|
Hormone replacement therapy
|
1 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Hyperlipidaemia medication compliant
|
96 Participants
n=5 Participants
|
93 Participants
n=7 Participants
|
189 Participants
n=5 Participants
|
|
Antiplatelet therapy
|
67 Participants
n=5 Participants
|
77 Participants
n=7 Participants
|
144 Participants
n=5 Participants
|
|
Diabetes
|
72 Participants
n=5 Participants
|
67 Participants
n=7 Participants
|
139 Participants
n=5 Participants
|
|
Hypertension
|
241 Participants
n=5 Participants
|
240 Participants
n=7 Participants
|
481 Participants
n=5 Participants
|
|
Other cardiovascular disease
|
38 Participants
n=5 Participants
|
34 Participants
n=7 Participants
|
72 Participants
n=5 Participants
|
|
GCS score at randomization
3-8
|
64 Participants
n=5 Participants
|
63 Participants
n=7 Participants
|
127 Participants
n=5 Participants
|
|
GCS score at randomization
9-12
|
111 Participants
n=5 Participants
|
108 Participants
n=7 Participants
|
219 Participants
n=5 Participants
|
|
GCS score at randomization
13-15
|
75 Participants
n=5 Participants
|
78 Participants
n=7 Participants
|
153 Participants
n=5 Participants
|
|
NIHSS score at randomization
|
19 Units on a scale
n=5 Participants
|
19 Units on a scale
n=7 Participants
|
19 Units on a scale
n=5 Participants
|
|
Diagnostic CT at presentation - IntraCerebral Hemorrhage (ICH) volume (mL)
|
42.7 mL
n=5 Participants
|
41.5 mL
n=7 Participants
|
41.8 mL
n=5 Participants
|
|
Diagnostic CT at presentation - IntraVentricular Hemorrhage (IVH) volume (mL)
|
0 mL
n=5 Participants
|
0 mL
n=7 Participants
|
0 mL
n=5 Participants
|
|
Stability CT(last CT before randomization) IntraCerebral Hemorrhage (ICH) volume (mL)
|
45.8 mL
n=5 Participants
|
45.3 mL
n=7 Participants
|
45.6 mL
n=5 Participants
|
|
Stability CT(last CT before randomization) IntraVentricular Hemorrhage (IVH) volume (mL)
|
0.3 mL
n=5 Participants
|
0.4 mL
n=7 Participants
|
0.4 mL
n=5 Participants
|
|
Ventilated at randomization
|
107 Participants
n=5 Participants
|
102 Participants
n=7 Participants
|
209 Participants
n=5 Participants
|
|
Blood pressure at presentation
Systolic BP (mm Hg)
|
177 mm Hg
n=5 Participants
|
176 mm Hg
n=7 Participants
|
177 mm Hg
n=5 Participants
|
|
Blood pressure at presentation
Diastolic BP (mm Hg)
|
99 mm Hg
n=5 Participants
|
98 mm Hg
n=7 Participants
|
98 mm Hg
n=5 Participants
|
|
Blood pressure at randomization
Systolic BP (mm Hg)
|
138 mm Hg
n=5 Participants
|
138 mm Hg
n=7 Participants
|
138 mm Hg
n=5 Participants
|
|
Blood pressure at randomization
Diastolic BP (mm Hg)
|
70 mm Hg
n=5 Participants
|
69 mm Hg
n=7 Participants
|
69 mm Hg
n=5 Participants
|
|
Time from stroke to diagnostic CT (h)
|
2.2 Hours
n=5 Participants
|
1.9 Hours
n=7 Participants
|
2.0 Hours
n=5 Participants
|
|
Time from stroke to stability CT (h)
|
36.4 Hours
n=5 Participants
|
36.3 Hours
n=7 Participants
|
36.3 Hours
n=5 Participants
|
|
Clot location
Deep
|
163 Participants
n=5 Participants
|
144 Participants
n=7 Participants
|
307 Participants
n=5 Participants
|
|
Clot location
Lobar
|
87 Participants
n=5 Participants
|
105 Participants
n=7 Participants
|
192 Participants
n=5 Participants
|
|
mRS score before stroke
0
|
230 Participants
n=5 Participants
|
233 Participants
n=7 Participants
|
463 Participants
n=5 Participants
|
|
mRS score before stroke
1
|
20 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
36 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 365Population: Includes participants with mRS scores available at day 365. Number and proportions reported refer to number of participants and proportions with Modified Rankin Score 0-3
Dichotomized, adjudicated, cross-sectional modified Rankin Scale (mRS) score 0-3 vs. 4-6 at 365 days post-ictus, adjusting for baseline (pre-randomization) variables used in covariate adaptive randomization as well as the clinically established severity variables IVH size and ICH location (lobar or deep). Ictus refers to symptom onset. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from: 0=No symptoms at all, 1=No significant disability, 2=Slight disability, 3=Moderate disability, 4=Moderately severe disability, 5=Severe disability and 6=death. Dichotomized scores are: 0-3=No symptoms to moderate disability requiring some assistance; 4-6=Moderately severe disability requiring complete assistance to death.
Outcome measures
| Measure |
Medical Management
n=240 Participants
Subjects randomized to medical management will receive the standard medical therapies for the treatment of intracerebral hemorrhage, which includes ICU care only and no planned surgical intervention.
|
MIS Plus Rt-PA Management
n=249 Participants
Subjects randomized to the MIS plus rt-PA management arm will undergo minimally invasive surgery followed by up to 9 doses of 1.0 mg of rt-PA (Activase/Alteplase/CathFlo) for intracerebral hemorrhage clot resolution.
rt-PA: Up to 9 doses of 1.0 mg of rt-PA will be administered through the catheter that was placed directly into the intracerebral hemorrhage using minimally invasive surgery.
|
|---|---|---|
|
Dichotomized, Adjudicated Modified Rankin Scale Score 0-3 vs. 4-6 at 365 Days Post Ictus (Adjusted)
mRS 0-3
|
100 Participants
|
110 Participants
|
|
Dichotomized, Adjudicated Modified Rankin Scale Score 0-3 vs. 4-6 at 365 Days Post Ictus (Adjusted)
mRS 4-6
|
140 Participants
|
139 Participants
|
SECONDARY outcome
Timeframe: Day 365Population: Those with non-missing mRS scores at 365 days post ictus
Dichotomized, cross-sectional extended Glasgow Outcome Scale (eGOS) score upper good recovery (UGR) through upper severe disability (US) vs. lower severe disability (LS) through death at 365 days post ictus, adjusting for baseline (pre-randomization) variables used in covariate adaptive randomization as well as the clinically established severity variables IVH size and ICH location (lobar or deep). The eGOS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored as: 1=Death, 2=Vegetative state, 3=Lower severe disability, 4=Upper severe disability, 5=Lower moderate disability, 6=Upper moderate disability, 7=Lower good recovery, 8=Upper good recovery. Dichotomous variable coding is as follows: 1=codes 4-8, 0=codes 1-3.
Outcome measures
| Measure |
Medical Management
n=234 Participants
Subjects randomized to medical management will receive the standard medical therapies for the treatment of intracerebral hemorrhage, which includes ICU care only and no planned surgical intervention.
|
MIS Plus Rt-PA Management
n=244 Participants
Subjects randomized to the MIS plus rt-PA management arm will undergo minimally invasive surgery followed by up to 9 doses of 1.0 mg of rt-PA (Activase/Alteplase/CathFlo) for intracerebral hemorrhage clot resolution.
rt-PA: Up to 9 doses of 1.0 mg of rt-PA will be administered through the catheter that was placed directly into the intracerebral hemorrhage using minimally invasive surgery.
|
|---|---|---|
|
Dichotomized Extended Glasgow Outcome Scale (eGOS) Score UGR-US vs. LS-Death at 365 Days Post Ictus (Adjusted)
eGOS UGR-US (4-8)
|
84 Participants
|
94 Participants
|
|
Dichotomized Extended Glasgow Outcome Scale (eGOS) Score UGR-US vs. LS-Death at 365 Days Post Ictus (Adjusted)
eGOS LS-Death (1-3)
|
150 Participants
|
150 Participants
|
SECONDARY outcome
Timeframe: Day 365By group comparison of mortality from ictus to 365 days adjusted for baseline severity.
Outcome measures
| Measure |
Medical Management
n=249 Participants
Subjects randomized to medical management will receive the standard medical therapies for the treatment of intracerebral hemorrhage, which includes ICU care only and no planned surgical intervention.
|
MIS Plus Rt-PA Management
n=250 Participants
Subjects randomized to the MIS plus rt-PA management arm will undergo minimally invasive surgery followed by up to 9 doses of 1.0 mg of rt-PA (Activase/Alteplase/CathFlo) for intracerebral hemorrhage clot resolution.
rt-PA: Up to 9 doses of 1.0 mg of rt-PA will be administered through the catheter that was placed directly into the intracerebral hemorrhage using minimally invasive surgery.
|
|---|---|---|
|
All Cause Mortality Longitudinally From Ictus to 365 Days (Adjusted)
|
62 Participants
|
48 Participants
|
SECONDARY outcome
Timeframe: 24 hours after last dosePopulation: Includes patients who survived through the dosing period
Relationship between clot removal as an Area Under the Curve (AUC) clot-assessment that estimates the time-averaged clot volume from ictus to end of treatment (EOT i.e. 24 hours after last dose) as AUC clot exposure and functional outcome (proportion 0-3 Modified Rankin Scale (mRS)).
Outcome measures
| Measure |
Medical Management
n=239 Participants
Subjects randomized to medical management will receive the standard medical therapies for the treatment of intracerebral hemorrhage, which includes ICU care only and no planned surgical intervention.
|
MIS Plus Rt-PA Management
n=246 Participants
Subjects randomized to the MIS plus rt-PA management arm will undergo minimally invasive surgery followed by up to 9 doses of 1.0 mg of rt-PA (Activase/Alteplase/CathFlo) for intracerebral hemorrhage clot resolution.
rt-PA: Up to 9 doses of 1.0 mg of rt-PA will be administered through the catheter that was placed directly into the intracerebral hemorrhage using minimally invasive surgery.
|
|---|---|---|
|
Clot Removal (Amount of Residual Blood)
mRS 0-3
|
4.11 10mL x days
Standard Deviation 1.35
|
2.69 10mL x days
Standard Deviation 1.11
|
|
Clot Removal (Amount of Residual Blood)
mRS 4-6
|
5.26 10mL x days
Standard Deviation 1.82
|
3.32 10mL x days
Standard Deviation 1.33
|
SECONDARY outcome
Timeframe: During 365 days of follow-upPopulation: Includes only patients with cumulative home days at any time during the 365 days of follow-up.
By group comparison of cumulative days at home during the 365 days post ictus.
Outcome measures
| Measure |
Medical Management
n=157 Participants
Subjects randomized to medical management will receive the standard medical therapies for the treatment of intracerebral hemorrhage, which includes ICU care only and no planned surgical intervention.
|
MIS Plus Rt-PA Management
n=166 Participants
Subjects randomized to the MIS plus rt-PA management arm will undergo minimally invasive surgery followed by up to 9 doses of 1.0 mg of rt-PA (Activase/Alteplase/CathFlo) for intracerebral hemorrhage clot resolution.
rt-PA: Up to 9 doses of 1.0 mg of rt-PA will be administered through the catheter that was placed directly into the intracerebral hemorrhage using minimally invasive surgery.
|
|---|---|---|
|
Patient Disposition: Home Days Over 365 Days Time From Ictus.
|
300 Days
Interval 232.0 to 328.0
|
306 Days
Interval 237.0 to 329.0
|
SECONDARY outcome
Timeframe: Day 365Patient disposition: By group comparison of residential location at day 365 post ictus adjusted for baseline severity. Good locations refers to home and rehabilitation; and bad locations refers to acute care, long-term care and death.
Outcome measures
| Measure |
Medical Management
n=249 Participants
Subjects randomized to medical management will receive the standard medical therapies for the treatment of intracerebral hemorrhage, which includes ICU care only and no planned surgical intervention.
|
MIS Plus Rt-PA Management
n=250 Participants
Subjects randomized to the MIS plus rt-PA management arm will undergo minimally invasive surgery followed by up to 9 doses of 1.0 mg of rt-PA (Activase/Alteplase/CathFlo) for intracerebral hemorrhage clot resolution.
rt-PA: Up to 9 doses of 1.0 mg of rt-PA will be administered through the catheter that was placed directly into the intracerebral hemorrhage using minimally invasive surgery.
|
|---|---|---|
|
Patient Disposition: Patient Location at 365 Days Post Ictus (i.e., Good vs. Bad Location) (Adjusted)
Good Location
|
151 Participants
|
163 Participants
|
|
Patient Disposition: Patient Location at 365 Days Post Ictus (i.e., Good vs. Bad Location) (Adjusted)
Bad location
|
98 Participants
|
87 Participants
|
SECONDARY outcome
Timeframe: Day 180Population: Includes patients who were not lost to followup at day 180
Dichotomized, adjudicated, cross-sectional modified Rankin Scale (mRS) score 0-3 vs. 4-6 at 180 days post-ictus, adjusting for baseline (pre-randomization) variables used in covariate adaptive randomization as well as the clinically established severity variables IVH size and ICH location (lobar or deep). The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from: 0=No symptoms at all, 1=No significant disability, 2=Slight disability, 3=Moderate disability, 4=Moderately severe disability, 5=Severe disability and 6=death. Dichotomized scores are: 0-3=No symptoms to moderate disability requiring some assistance; 4-6=Moderately severe disability requiring complete assistance to death
Outcome measures
| Measure |
Medical Management
n=243 Participants
Subjects randomized to medical management will receive the standard medical therapies for the treatment of intracerebral hemorrhage, which includes ICU care only and no planned surgical intervention.
|
MIS Plus Rt-PA Management
n=250 Participants
Subjects randomized to the MIS plus rt-PA management arm will undergo minimally invasive surgery followed by up to 9 doses of 1.0 mg of rt-PA (Activase/Alteplase/CathFlo) for intracerebral hemorrhage clot resolution.
rt-PA: Up to 9 doses of 1.0 mg of rt-PA will be administered through the catheter that was placed directly into the intracerebral hemorrhage using minimally invasive surgery.
|
|---|---|---|
|
Dichotomized, Adjudicated, Cross-sectional Modified Rankin Scale (mRS) Score 0-3 vs. 4-6 180 Days Post Ictus (Adjusted)
mRS 0-3
|
93 Participants
|
99 Participants
|
|
Dichotomized, Adjudicated, Cross-sectional Modified Rankin Scale (mRS) Score 0-3 vs. 4-6 180 Days Post Ictus (Adjusted)
mRS 4-6
|
150 Participants
|
151 Participants
|
SECONDARY outcome
Timeframe: Day 180Population: Patients were included if they were not lost to followup at day 180
Dichotomized, cross-sectional extended Glasgow Outcome Scale (eGOS) score upper good recovery (UGR) through upper severe disability (US) vs. lower severe disability (LS) through death at 180 days post ictus, adjusting for baseline (pre-randomization) variables used in covariate adaptive randomization as well as the clinically established severity variables IVH size and ICH location (lobar or deep). The eGOS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored as: 1=Death, 2=Vegetative state, 3=Lower severe disability, 4=Upper severe disability, 5=Lower moderate disability, 6=Upper moderate disability, 7=Lower good recovery, 8=Upper good recovery. Dichotomous variable coding is as follows: 1=codes 4-8, 0=codes 1-3.
Outcome measures
| Measure |
Medical Management
n=243 Participants
Subjects randomized to medical management will receive the standard medical therapies for the treatment of intracerebral hemorrhage, which includes ICU care only and no planned surgical intervention.
|
MIS Plus Rt-PA Management
n=250 Participants
Subjects randomized to the MIS plus rt-PA management arm will undergo minimally invasive surgery followed by up to 9 doses of 1.0 mg of rt-PA (Activase/Alteplase/CathFlo) for intracerebral hemorrhage clot resolution.
rt-PA: Up to 9 doses of 1.0 mg of rt-PA will be administered through the catheter that was placed directly into the intracerebral hemorrhage using minimally invasive surgery.
|
|---|---|---|
|
Dichotomized Extended Glasgow Outcome Scale (eGOS) Score UGR-US vs. LS-Death at 180 Days Post Ictus (Adjusted)
eGOS UGR-US (4-8)
|
76 Participants
|
81 Participants
|
|
Dichotomized Extended Glasgow Outcome Scale (eGOS) Score UGR-US vs. LS-Death at 180 Days Post Ictus (Adjusted)
eGOS LS-Death (1-3)
|
167 Participants
|
169 Participants
|
SECONDARY outcome
Timeframe: Up to 365 daysPopulation: Includes patients with cumulative ICU days during the 365 days of follow-up
By group comparison of cumulative number of days in the Intensive Care Unit (ICU) in a hospital
Outcome measures
| Measure |
Medical Management
n=238 Participants
Subjects randomized to medical management will receive the standard medical therapies for the treatment of intracerebral hemorrhage, which includes ICU care only and no planned surgical intervention.
|
MIS Plus Rt-PA Management
n=240 Participants
Subjects randomized to the MIS plus rt-PA management arm will undergo minimally invasive surgery followed by up to 9 doses of 1.0 mg of rt-PA (Activase/Alteplase/CathFlo) for intracerebral hemorrhage clot resolution.
rt-PA: Up to 9 doses of 1.0 mg of rt-PA will be administered through the catheter that was placed directly into the intracerebral hemorrhage using minimally invasive surgery.
|
|---|---|---|
|
Type and Intensity of ICU Management: ICU Days
|
10 Days
Interval 5.0 to 16.0
|
10 Days
Interval 7.0 to 17.0
|
SECONDARY outcome
Timeframe: Up to 365 daysBy group comparison of total number of days in the hospital
Outcome measures
| Measure |
Medical Management
n=249 Participants
Subjects randomized to medical management will receive the standard medical therapies for the treatment of intracerebral hemorrhage, which includes ICU care only and no planned surgical intervention.
|
MIS Plus Rt-PA Management
n=250 Participants
Subjects randomized to the MIS plus rt-PA management arm will undergo minimally invasive surgery followed by up to 9 doses of 1.0 mg of rt-PA (Activase/Alteplase/CathFlo) for intracerebral hemorrhage clot resolution.
rt-PA: Up to 9 doses of 1.0 mg of rt-PA will be administered through the catheter that was placed directly into the intracerebral hemorrhage using minimally invasive surgery.
|
|---|---|---|
|
Type and Intensity of ICU Management: Hospital Days
|
17 Days
Interval 10.0 to 25.0
|
17 Days
Interval 13.0 to 27.0
|
SECONDARY outcome
Timeframe: Day 365Population: Includes patients who survived or were not lost to followup through 365 days
By group comparison of EQ-VAS at day 365 post ictus. The EuroQol Visual Analogue Scale (EQ-VAS) is a self-reported measure of health status. It is a marked scale where subjects draw a line to indicate their health, with end points of 0 (the worst health you can imagine) and 100 (the best health you can imagine).
Outcome measures
| Measure |
Medical Management
n=164 Participants
Subjects randomized to medical management will receive the standard medical therapies for the treatment of intracerebral hemorrhage, which includes ICU care only and no planned surgical intervention.
|
MIS Plus Rt-PA Management
n=183 Participants
Subjects randomized to the MIS plus rt-PA management arm will undergo minimally invasive surgery followed by up to 9 doses of 1.0 mg of rt-PA (Activase/Alteplase/CathFlo) for intracerebral hemorrhage clot resolution.
rt-PA: Up to 9 doses of 1.0 mg of rt-PA will be administered through the catheter that was placed directly into the intracerebral hemorrhage using minimally invasive surgery.
|
|---|---|---|
|
EQ-VAS
|
70 score on a scale
Interval 50.0 to 80.0
|
70 score on a scale
Interval 50.0 to 80.0
|
SECONDARY outcome
Timeframe: Day 365Population: Patients were included if they survived or were not lost to followup through 365 days
By group comparison of EQ-5D at day 365 post ictus. The EuroQol 5 Dimensional Scale (Eq-5D) is a self-reported measure of health status. It is arranged to assess domains related to mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. For each domain, codes were 1=no problems, 2=some problems, 3=extreme problems, and 9=unknown. Having a problem in at least 1 domain was coded as 1 (originally represented by 2 or 3) and no problems as 0 (originally represented by 1) .
Outcome measures
| Measure |
Medical Management
n=170 Participants
Subjects randomized to medical management will receive the standard medical therapies for the treatment of intracerebral hemorrhage, which includes ICU care only and no planned surgical intervention.
|
MIS Plus Rt-PA Management
n=192 Participants
Subjects randomized to the MIS plus rt-PA management arm will undergo minimally invasive surgery followed by up to 9 doses of 1.0 mg of rt-PA (Activase/Alteplase/CathFlo) for intracerebral hemorrhage clot resolution.
rt-PA: Up to 9 doses of 1.0 mg of rt-PA will be administered through the catheter that was placed directly into the intracerebral hemorrhage using minimally invasive surgery.
|
|---|---|---|
|
EuroQol 5 Dimensional Scale (EQ-5D)
Any problem
|
155 Participants
|
176 Participants
|
|
EuroQol 5 Dimensional Scale (EQ-5D)
No problem
|
15 Participants
|
16 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 7Mortality and Safety events: By group comparison of mortality within the first 7 days post randomization.
Outcome measures
| Measure |
Medical Management
n=249 Participants
Subjects randomized to medical management will receive the standard medical therapies for the treatment of intracerebral hemorrhage, which includes ICU care only and no planned surgical intervention.
|
MIS Plus Rt-PA Management
n=250 Participants
Subjects randomized to the MIS plus rt-PA management arm will undergo minimally invasive surgery followed by up to 9 doses of 1.0 mg of rt-PA (Activase/Alteplase/CathFlo) for intracerebral hemorrhage clot resolution.
rt-PA: Up to 9 doses of 1.0 mg of rt-PA will be administered through the catheter that was placed directly into the intracerebral hemorrhage using minimally invasive surgery.
|
|---|---|---|
|
Mortality and Safety Events: First-week (Operative) Mortality
|
10 Participants
|
2 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 30By group comparison of mortality from all causes within the first 30 days post randomization.
Outcome measures
| Measure |
Medical Management
n=249 Participants
Subjects randomized to medical management will receive the standard medical therapies for the treatment of intracerebral hemorrhage, which includes ICU care only and no planned surgical intervention.
|
MIS Plus Rt-PA Management
n=250 Participants
Subjects randomized to the MIS plus rt-PA management arm will undergo minimally invasive surgery followed by up to 9 doses of 1.0 mg of rt-PA (Activase/Alteplase/CathFlo) for intracerebral hemorrhage clot resolution.
rt-PA: Up to 9 doses of 1.0 mg of rt-PA will be administered through the catheter that was placed directly into the intracerebral hemorrhage using minimally invasive surgery.
|
|---|---|---|
|
Mortality and Safety Events: All Cause Mortality
|
37 Participants
|
23 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 72 hours after last doseBy group comparison of the percentage of subjects experiencing one or more adjudicated symptomatic brain bleeding events within the first 30 days post randomization.
Outcome measures
| Measure |
Medical Management
n=249 Participants
Subjects randomized to medical management will receive the standard medical therapies for the treatment of intracerebral hemorrhage, which includes ICU care only and no planned surgical intervention.
|
MIS Plus Rt-PA Management
n=250 Participants
Subjects randomized to the MIS plus rt-PA management arm will undergo minimally invasive surgery followed by up to 9 doses of 1.0 mg of rt-PA (Activase/Alteplase/CathFlo) for intracerebral hemorrhage clot resolution.
rt-PA: Up to 9 doses of 1.0 mg of rt-PA will be administered through the catheter that was placed directly into the intracerebral hemorrhage using minimally invasive surgery.
|
|---|---|---|
|
Mortality and Safety Events: Adjudicated Symptomatic Brain Bleeding Within 72 Hours After Last Dose
|
3 Participants
|
6 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 30By group comparison of the percentage of subjects experiencing one or more adjudicated brain bacterial infection events within the first 30 days post randomization.
Outcome measures
| Measure |
Medical Management
n=249 Participants
Subjects randomized to medical management will receive the standard medical therapies for the treatment of intracerebral hemorrhage, which includes ICU care only and no planned surgical intervention.
|
MIS Plus Rt-PA Management
n=250 Participants
Subjects randomized to the MIS plus rt-PA management arm will undergo minimally invasive surgery followed by up to 9 doses of 1.0 mg of rt-PA (Activase/Alteplase/CathFlo) for intracerebral hemorrhage clot resolution.
rt-PA: Up to 9 doses of 1.0 mg of rt-PA will be administered through the catheter that was placed directly into the intracerebral hemorrhage using minimally invasive surgery.
|
|---|---|---|
|
Mortality and Safety Events: Adjudicated Bacterial Brain Infection
|
0 Participants
|
2 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 30By group comparison of the total number of adjudicated serious adverse events that occurred within the first 30 days post randomization.
Outcome measures
| Measure |
Medical Management
n=249 Participants
Subjects randomized to medical management will receive the standard medical therapies for the treatment of intracerebral hemorrhage, which includes ICU care only and no planned surgical intervention.
|
MIS Plus Rt-PA Management
n=250 Participants
Subjects randomized to the MIS plus rt-PA management arm will undergo minimally invasive surgery followed by up to 9 doses of 1.0 mg of rt-PA (Activase/Alteplase/CathFlo) for intracerebral hemorrhage clot resolution.
rt-PA: Up to 9 doses of 1.0 mg of rt-PA will be administered through the catheter that was placed directly into the intracerebral hemorrhage using minimally invasive surgery.
|
|---|---|---|
|
Mortality and Safety Events: Total Serious Adverse Events (SAE) at 30 Days
|
136 Number of events
|
123 Number of events
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 30By group comparison of the total number of adjudicated adverse events (AE) and serious adverse events (SAE) across all coded organ systems that occurred within the first 30 days post ictus.
Outcome measures
| Measure |
Medical Management
n=249 Participants
Subjects randomized to medical management will receive the standard medical therapies for the treatment of intracerebral hemorrhage, which includes ICU care only and no planned surgical intervention.
|
MIS Plus Rt-PA Management
n=250 Participants
Subjects randomized to the MIS plus rt-PA management arm will undergo minimally invasive surgery followed by up to 9 doses of 1.0 mg of rt-PA (Activase/Alteplase/CathFlo) for intracerebral hemorrhage clot resolution.
rt-PA: Up to 9 doses of 1.0 mg of rt-PA will be administered through the catheter that was placed directly into the intracerebral hemorrhage using minimally invasive surgery.
|
|---|---|---|
|
Mortality and Safety Events: Summary of AE and SAE by MedDRA Code and Grouped by Organ System Within the First 30 Days Post Ictus
Serious Adverse Events
|
136 Number of events
|
123 Number of events
|
|
Mortality and Safety Events: Summary of AE and SAE by MedDRA Code and Grouped by Organ System Within the First 30 Days Post Ictus
Adverse Events
|
378 Number of events
|
477 Number of events
|
Adverse Events
MIS Plus Rt-PA Management
Serious events: 75 serious events
Other events: 205 other events
Deaths: 48 deaths
Medical Management
Serious events: 84 serious events
Other events: 169 other events
Deaths: 62 deaths
Serious adverse events
| Measure |
MIS Plus Rt-PA Management
n=250 participants at risk
Subjects randomized to the MIS plus rt-PA management arm will undergo minimally invasive surgery followed by up to 9 doses of 1.0 mg of rt-PA (Activase/Alteplase/CathFlo) for intracerebral hemorrhage clot resolution.
rt-PA: Up to 9 doses of 1.0 mg of rt-PA will be administered through the catheter that was placed directly into the intracerebral hemorrhage using minimally invasive surgery.
|
Medical Management
n=249 participants at risk
Subjects randomized to medical management will receive the standard medical therapies for the treatment of intracerebral hemorrhage, which includes ICU care only and no planned surgical intervention.
|
|---|---|---|
|
Cardiac disorders
Cardiac disorders
|
1.2%
3/250 • Number of events 4 • 30 days post-ictus
|
0.40%
1/249 • Number of events 2 • 30 days post-ictus
|
|
Gastrointestinal disorders
Gastrointestinal disorders
|
1.2%
3/250 • Number of events 4 • 30 days post-ictus
|
1.6%
4/249 • Number of events 6 • 30 days post-ictus
|
|
General disorders
General disorders and administration site conditions
|
5.2%
13/250 • Number of events 13 • 30 days post-ictus
|
10.4%
26/249 • Number of events 27 • 30 days post-ictus
|
|
Infections and infestations
Non-neurological infections
|
0.80%
2/250 • Number of events 5 • 30 days post-ictus
|
1.6%
4/249 • Number of events 8 • 30 days post-ictus
|
|
Injury, poisoning and procedural complications
Injury, Poisoning and procedural complications
|
1.2%
3/250 • Number of events 3 • 30 days post-ictus
|
0.00%
0/249 • 30 days post-ictus
|
|
Metabolism and nutrition disorders
Metabolism and nutrition disorders
|
0.40%
1/250 • Number of events 1 • 30 days post-ictus
|
0.00%
0/249 • 30 days post-ictus
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms(Benign, malignant or unspecified
|
0.40%
1/250 • Number of events 1 • 30 days post-ictus
|
0.00%
0/249 • 30 days post-ictus
|
|
Nervous system disorders
Nervous system disorders
|
6.8%
17/250 • Number of events 41 • 30 days post-ictus
|
13.3%
33/249 • Number of events 62 • 30 days post-ictus
|
|
Psychiatric disorders
Psychiatric disorders
|
0.00%
0/250 • 30 days post-ictus
|
0.40%
1/249 • Number of events 2 • 30 days post-ictus
|
|
Renal and urinary disorders
Renal and urinary disorders
|
0.00%
0/250 • 30 days post-ictus
|
0.40%
1/249 • Number of events 4 • 30 days post-ictus
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disirders
|
10.4%
26/250 • Number of events 40 • 30 days post-ictus
|
5.6%
14/249 • Number of events 25 • 30 days post-ictus
|
|
Vascular disorders
Vascular disorders
|
2.4%
6/250 • Number of events 11 • 30 days post-ictus
|
0.00%
0/249 • 30 days post-ictus
|
Other adverse events
| Measure |
MIS Plus Rt-PA Management
n=250 participants at risk
Subjects randomized to the MIS plus rt-PA management arm will undergo minimally invasive surgery followed by up to 9 doses of 1.0 mg of rt-PA (Activase/Alteplase/CathFlo) for intracerebral hemorrhage clot resolution.
rt-PA: Up to 9 doses of 1.0 mg of rt-PA will be administered through the catheter that was placed directly into the intracerebral hemorrhage using minimally invasive surgery.
|
Medical Management
n=249 participants at risk
Subjects randomized to medical management will receive the standard medical therapies for the treatment of intracerebral hemorrhage, which includes ICU care only and no planned surgical intervention.
|
|---|---|---|
|
Blood and lymphatic system disorders
Blood and lymphatic system disorders
|
0.80%
2/250 • Number of events 3 • 30 days post-ictus
|
0.00%
0/249 • 30 days post-ictus
|
|
Cardiac disorders
Cardiac disorders
|
1.2%
3/250 • Number of events 15 • 30 days post-ictus
|
2.0%
5/249 • Number of events 11 • 30 days post-ictus
|
|
Gastrointestinal disorders
Gastrointestinal disorders
|
2.0%
5/250 • Number of events 12 • 30 days post-ictus
|
2.8%
7/249 • Number of events 17 • 30 days post-ictus
|
|
General disorders
General disorders and administration site conditions
|
6.8%
17/250 • Number of events 53 • 30 days post-ictus
|
4.8%
12/249 • Number of events 42 • 30 days post-ictus
|
|
Hepatobiliary disorders
Hepatobiliary disorders
|
0.00%
0/250 • 30 days post-ictus
|
0.80%
2/249 • Number of events 2 • 30 days post-ictus
|
|
Immune system disorders
Immune system disorders
|
0.00%
0/250 • 30 days post-ictus
|
0.40%
1/249 • Number of events 1 • 30 days post-ictus
|
|
Infections and infestations
Infections, non-neurologic
|
3.6%
9/250 • Number of events 16 • 30 days post-ictus
|
10.0%
25/249 • Number of events 41 • 30 days post-ictus
|
|
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications
|
0.40%
1/250 • Number of events 4 • 30 days post-ictus
|
0.80%
2/249 • Number of events 3 • 30 days post-ictus
|
|
Investigations
Investigations
|
0.40%
1/250 • Number of events 12 • 30 days post-ictus
|
2.8%
7/249 • Number of events 20 • 30 days post-ictus
|
|
Metabolism and nutrition disorders
Metabolism and nutrition disorders
|
1.2%
3/250 • Number of events 17 • 30 days post-ictus
|
2.4%
6/249 • Number of events 20 • 30 days post-ictus
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorders
|
0.80%
2/250 • Number of events 3 • 30 days post-ictus
|
0.00%
0/249 • 30 days post-ictus
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms: benign, malignant, Unspecified (incl cysts and polyps)
|
0.40%
1/250 • Number of events 1 • 30 days post-ictus
|
0.40%
1/249 • Number of events 2 • 30 days post-ictus
|
|
Nervous system disorders
Nervous system disorders
|
43.2%
108/250 • Number of events 216 • 30 days post-ictus
|
18.9%
47/249 • Number of events 107 • 30 days post-ictus
|
|
Psychiatric disorders
Psychiatric disorders
|
2.4%
6/250 • Number of events 14 • 30 days post-ictus
|
2.0%
5/249 • Number of events 13 • 30 days post-ictus
|
|
Renal and urinary disorders
Renal and urinary disorders
|
1.2%
3/250 • Number of events 5 • 30 days post-ictus
|
0.80%
2/249 • Number of events 5 • 30 days post-ictus
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders
|
12.0%
30/250 • Number of events 67 • 30 days post-ictus
|
13.3%
33/249 • Number of events 62 • 30 days post-ictus
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders
|
0.00%
0/250 • 30 days post-ictus
|
0.40%
1/249 • Number of events 3 • 30 days post-ictus
|
|
Vascular disorders
Vascular disorders
|
5.6%
14/250 • Number of events 39 • 30 days post-ictus
|
5.2%
13/249 • Number of events 29 • 30 days post-ictus
|
Additional Information
Dr. Daniel F. Hanley
Johns Hopkins University Division of Brain Injury Outcomes
Phone: 4106146996
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place