A phase III, randomized, case-controlled, open-label, 500-subject clinical trial of minimally invasive surgery plus rt-PA in the treatment of intracerebral hemorrhage (ICH).
Primary Objectives: Efficacy: Demonstrate that minimally invasive surgery (MIS) plus recombinant tissue plasminogen activator (rt-PA) for three days improves functional outcome by a 12% increase in the modified Rankin Scale (mRS) score 0-3 compared to medically treated subjects assessed at 365 days. Secondary Objective: Demonstrate that the end of treatment volume and percent of ICH reduction from MIS+rt-PA is related to improved functional outcome, as compared to medically treated subjects. Safety: Demonstrate that early use of MIS+rt-PA for three days is safe for the treatment of ICH relative to rates of mortality, rebleeding, and infection in the medically treated subject at 30 days.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
499
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)
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.
Time frame: Day 365
Dichotomized Extended Glasgow Outcome Scale (eGOS) Score UGR-US vs. LS-Death at 365 Days Post Ictus (Adjusted)
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.
Time frame: Day 365
All Cause Mortality Longitudinally From Ictus to 365 Days (Adjusted)
By group comparison of mortality from ictus to 365 days adjusted for baseline severity.
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University of Alabama at Birmingham
Birmingham, Alabama, United States
Banner Good Samaritan Hospital
Phoenix, Arizona, United States
Barrow Neurological Institute
Phoenix, Arizona, United States
Mercy San Juan Medical Center
Carmichael, California, United States
Scripps Health
La Jolla, California, United States
University of California, Los Angeles
Los Angeles, California, United States
University of California, San Diego
San Diego, California, United States
Stanford University
Stanford, California, United States
Hartford Hospital
Hartford, Connecticut, United States
Yale University
New Haven, Connecticut, United States
...and 74 more locations
Time frame: Day 365
Clot Removal (Amount of Residual Blood)
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)).
Time frame: 24 hours after last dose
Patient Disposition: Home Days Over 365 Days Time From Ictus.
By group comparison of cumulative days at home during the 365 days post ictus.
Time frame: During 365 days of follow-up
Patient Disposition: Patient Location at 365 Days Post Ictus (i.e., Good vs. Bad Location) (Adjusted)
Patient 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.
Time frame: Day 365
Dichotomized, Adjudicated, Cross-sectional Modified Rankin Scale (mRS) Score 0-3 vs. 4-6 180 Days Post Ictus (Adjusted)
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
Time frame: Day 180
Dichotomized Extended Glasgow Outcome Scale (eGOS) Score UGR-US vs. LS-Death at 180 Days Post Ictus (Adjusted)
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.
Time frame: Day 180
Type and Intensity of ICU Management: ICU Days
By group comparison of cumulative number of days in the Intensive Care Unit (ICU) in a hospital
Time frame: Up to 365 days
Type and Intensity of ICU Management: Hospital Days
By group comparison of total number of days in the hospital
Time frame: Up to 365 days
EQ-VAS
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).
Time frame: Day 365
EuroQol 5 Dimensional Scale (EQ-5D)
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) .
Time frame: Day 365