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Minimally Invasive Surgery and rtPA for Intracerebral Hemorrhage Evacuation (MISTIE)

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ClinicalTrials.gov Identifier: NCT00224770
Recruitment Status : Completed
First Posted : September 23, 2005
Results First Posted : June 18, 2015
Last Update Posted : June 18, 2015
Sponsor:
Collaborators:
National Institute of Neurological Disorders and Stroke (NINDS)
Genentech, Inc.
Emissary International LLC
Information provided by (Responsible Party):
Daniel Hanley, Johns Hopkins University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Intracerebral Hemorrhage
Interventions Drug: MIS+Cathflo Activase (drug)
Procedure: Intraoperative stereotactic CT-Guided Endoscopic Surgery
Enrollment 141

Recruitment Details 110 patients were randomized to the trial, and 31 were recruited as pilot patients.
Pre-assignment Details Each study center was required to demonstrate proficiency in the technical aspects of enrollment, stabilization, surgery, and drug administration. This proficiency was demonstrated on at least one pilot patient prior to randomization of the first patient in the investigational cohort of 110 randomized patients.
Arm/Group Title Medical Management MISTIE Surgical Management ICES Surgical Management
Hide Arm/Group Description Standard of care medical management as per American Heart Association (AHA) guidelines.

Minimally invasive surgery (MIS) with clot lysis with recombinant tissue plasminogen activator (rt-PA).

MIS+Cathflo Activase (drug): The intervention is a comparison of the safety and preliminary effectiveness of investigational minimally invasive surgery to place a catheter into an intracerebral hemorrhage blood clot and subsequent administration in sequential tiers of 0.3 or 1.0mg of rt-PA, CathFlo® through the catheter once every eight hours for up to 72 hours, in addition to best medical care.

This includes 54 intent-to-treat patients, and excludes 27 pilots.

Intraoperative stereotactic CT-Guided Endoscopic Surgery (ICES)

Mechanical intracerebral hemorrhage removal via an endoscope utilizing the same operative-targeting arm as MISTIE arm. Best medical care was provided, but no rt-PA was administered.

This includes 14 intent-to-treat patients, and excludes 4 pilots.

Period Title: Overall Study
Started 42 54 14
Completed 38 52 14
Not Completed 4 2 0
Reason Not Completed
Lost to Follow-up             4             2             0
Arm/Group Title Medical Management MISTIE Surgical Management ICES Surgical Management Total
Hide Arm/Group Description Standard of care medical management as per American Heart Association (AHA) guidelines.

Minimally invasive surgery (MIS) with clot lysis with recombinant tissue plasminogen activator (rt-PA).

MIS+Cathflo Activase (drug): The intervention is a comparison of the safety and preliminary effectiveness of investigational minimally invasive surgery to place a catheter into an intracerebral hemorrhage blood clot and subsequent administration in sequential tiers of 0.3 or 1.0mg of rt-PA, CathFlo®) through the catheter once every eight hours for up to 72 hours, in addition to best medical care.

This includes 54 intent-to-treat patients, and excludes 27 pilots.

Intraoperative stereotactic CT-Guided Endoscopic Surgery

Mechanical intracerebral hemorrhage removal via an endoscope utilizing the same operative-targeting arm as MISTIE arm. Best medical care was provided, but no rt-PA was administered.

This includes 14 intent-to-treat patients, and excludes 4 pilots.

Total of all reporting groups
Overall Number of Baseline Participants 42 54 14 110
Hide Baseline Analysis Population Description
The decision was made to exclude the pilot patients from the analysis...
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 42 participants 54 participants 14 participants 110 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
18
  42.9%
25
  46.3%
9
  64.3%
52
  47.3%
>=65 years
24
  57.1%
29
  53.7%
5
  35.7%
58
  52.7%
Age, Continuous  
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 42 participants 54 participants 14 participants 110 participants
62
(49.5 to 73)
60
(54 to 69)
59
(53.2 to 68.2)
61
(53.3 to 70)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 42 participants 54 participants 14 participants 110 participants
Female
14
  33.3%
19
  35.2%
5
  35.7%
38
  34.5%
Male
28
  66.7%
35
  64.8%
9
  64.3%
72
  65.5%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 42 participants 54 participants 14 participants 110 participants
United States 41 53 14 108
United Kingdom 1 1 0 2
1.Primary Outcome
Title Safety Outcome Number 1: Rate of Mortality
Hide Description Percentage of participants who died during the first 30 days after randomization.
Time Frame 30 days from randomization
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Medical Management MISTIE Surgical Management ICES Surgical Management
Hide Arm/Group Description:
Standard of care medical management as per American Heart Association (AHA) guidelines.

Minimally invasive surgery (MIS) with clot lysis with recombinant tissue plasminogen activator (rt-PA).

MIS+Cathflo Activase (drug): The intervention is a comparison of the safety and preliminary effectiveness of investigational minimally invasive surgery to place a catheter into an intracerebral hemorrhage blood clot and subsequent administration in sequential tiers of 0.3 or 1.0mg of rt-PA, CathFlo® through the catheter once every eight hours for up to 72 hours, in addition to best medical care.

This includes 54 intent-to-treat patients, and excludes 27 pilots.

Intraoperative stereotactic CT-Guided Endoscopic Surgery (ICES)

Mechanical intracerebral hemorrhage removal via an endoscope utilizing the same operative-targeting arm as MISTIE arm. Best medical care was provided, but no rt-PA was administered.

This includes 14 intent-to-treat patients, and excludes 4 pilots.

Overall Number of Participants Analyzed 42 54 14
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: percentage of participants
9.5
(3.3 to 20.5)
14.8
(7.6 to 25.1)
7.1
(0.4 to 29.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Medical Management, MISTIE Surgical Management
Comments Null hypothesis is that rate of mortality within 30 days is the same between the two groups. The alternative hypothesis tests whether MISTIE surgical management has a higher rate of mortality than the medical arm.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.324
Comments [Not Specified]
Method Fisher Exact
Comments One-sided test
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 5.3
Confidence Interval (1-Sided) 95%
16.2
Parameter Dispersion
Type: Standard Error of the mean
Value: 6.6
Estimation Comments MISTIE rate=14.8, 95% upper limit=25.1; medical rate=9.5, 95% upper limit=20.5; comparison considers MISTIE rate minus medical rate.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Medical Management, ICES Surgical Management
Comments Null hypothesis is that rate of mortality within 30 days is the same between the two groups. The alternative hypothesis tests whether ICES surgical management has a higher rate of mortality than the medical arm.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.633
Comments [Not Specified]
Method Fisher Exact
Comments One-sided test
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -2.4
Confidence Interval (1-Sided) 95%
11.2
Parameter Dispersion
Type: Standard Error of the mean
Value: 8.2
Estimation Comments ICES rate=7.1, 95% upper limit=29.7; medical rate=9.5, 95% upper limit=20.5; comparison considers ICES rate minus medical rate.
2.Primary Outcome
Title Safety Outcome Number 2: Rate of Procedure-related Mortality
Hide Description Percentage of participants who died during the first 7 days after randomization.
Time Frame 7 days from randomization
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Medical Management MISTIE Surgical Management ICES Surgical Management
Hide Arm/Group Description:
Standard of care medical management as per American Heart Association (AHA) guidelines.

Minimally invasive surgery (MIS) with clot lysis with recombinant tissue plasminogen activator (rt-PA).

MIS+Cathflo Activase (drug): The intervention is a comparison of the safety and preliminary effectiveness of investigational minimally invasive surgery to place a catheter into an intracerebral hemorrhage blood clot and subsequent administration in sequential tiers of 0.3 or 1.0mg of rt-PA, CathFlo® through the catheter once every eight hours for up to 72 hours, in addition to best medical care.

This includes 54 intent-to-treat patients, and excludes 27 pilots.

Intraoperative stereotactic CT-Guided Endoscopic Surgery (ICES)

Mechanical intracerebral hemorrhage removal via an endoscope utilizing the same operative-targeting arm as MISTIE arm. Best medical care was provided, but no rt-PA was administered.

This includes 14 intent-to-treat patients, and excludes 4 pilots.

Overall Number of Participants Analyzed 42 54 14
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: percentage of participants
0
(0 to 6.9)
5.6
(1.5 to 13.7)
0
(0 to 19.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Medical Management, MISTIE Surgical Management
Comments Null hypothesis is that rate of procedure-related mortality within 7 days is the same between the two groups. The alternative hypothesis tests whether MISTIE surgical management has a higher rate of procedure-related mortality than the medical arm.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.174
Comments [Not Specified]
Method Fisher Exact
Comments One-sided test
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 5.6
Confidence Interval (1-Sided) 95%
11.7
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.1
Estimation Comments MISTIE rate=5.6, 95% upper limit=13.7; medical rate=0.0, 95% upper limit=6.9; comparison considers MISTIE rate minus medical rate.
3.Primary Outcome
Title Safety Outcome Number 3: Rate of Cerebritis, Meningitis, Bacterial Ventriculitis
Hide Description Percentage of participants who had a bacterial brain infection (cerebritis, meningitis, ventriculitis) within 30 days of randomization.
Time Frame 30 days from randomization
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Medical Management MISTIE Surgical Management ICES Surgical Management
Hide Arm/Group Description:
Standard of care medical management as per American Heart Association (AHA) guidelines.

Minimally invasive surgery (MIS) with clot lysis with recombinant tissue plasminogen activator (rt-PA).

MIS+Cathflo Activase (drug): The intervention is a comparison of the safety and preliminary effectiveness of investigational minimally invasive surgery to place a catheter into an intracerebral hemorrhage blood clot and subsequent administration in sequential tiers of 0.3 or 1.0mg of rt-PA, CathFlo® through the catheter once every eight hours for up to 72 hours, in addition to best medical care.

This includes 54 intent-to-treat patients, and excludes 27 pilots.

Intraoperative stereotactic CT-Guided Endoscopic Surgery (ICES)

Mechanical intracerebral hemorrhage removal via an endoscope utilizing the same operative-targeting arm as MISTIE arm. Best medical care was provided, but no rt-PA was administered.

This includes 14 intent-to-treat patients, and excludes 4 pilots.

Overall Number of Participants Analyzed 42 54 14
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: percentage of participants
2.4
(0.1 to 10.8)
0
(0 to 5.4)
0
(0 to 19.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Medical Management, MISTIE Surgical Management
Comments Null hypothesis is that rate of cerebritis, meningitis and ventriculitis within 30 days is the same between the two groups. The alternative hypothesis tests whether MISTIE surgical management has a higher rate of these infections than medical.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.437
Comments [Not Specified]
Method Fisher Exact
Comments One-sided test
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -2.4
Confidence Interval (1-Sided) 95%
1.5
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.4
Estimation Comments MISTIE rate=0.0, 95% upper limit=5.4; medical rate=2.4, 95% upper limit=10.8; comparison considers MISTIE rate minus medical rate.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Medical Management, ICES Surgical Management
Comments Null hypothesis is that rate of cerebritis, meningitis and ventriculitis within 30 days is the same between the two groups. The alternative hypothesis tests whether ICES surgical management has a higher rate of these infections than medical.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.750
Comments [Not Specified]
Method Fisher Exact
Comments One-sided test
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -2.4
Confidence Interval (1-Sided) 95%
1.5
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.4
Estimation Comments ICES rate=0.0, 95% upper limit=19.3; medical rate=2.4, 95% upper limit=10.8; comparison considers ICES rate minus medical rate.
4.Primary Outcome
Title Safety Outcome Number 4: Rate of Symptomatic Rebleeding
Hide Description The difference in the rate of symptomatic rebleeding 72 hours post last dose.
Time Frame 72 hours post last dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Medical Management MISTIE Surgical Management ICES Surgical Management
Hide Arm/Group Description:
Standard of care medical management as per American Heart Association (AHA) guidelines.

Minimally invasive surgery (MIS) with clot lysis with recombinant tissue plasminogen activator (rt-PA).

MIS+Cathflo Activase (drug): The intervention is a comparison of the safety and preliminary effectiveness of investigational minimally invasive surgery to place a catheter into an intracerebral hemorrhage blood clot and subsequent administration in sequential tiers of 0.3 or 1.0mg of rt-PA, CathFlo® through the catheter once every eight hours for up to 72 hours, in addition to best medical care.

This includes 54 intent-to-treat patients, and excludes 27 pilots.

Intraoperative stereotactic CT-Guided Endoscopic Surgery (ICES)

Mechanical intracerebral hemorrhage removal via an endoscope utilizing the same operative targeting technique as the MISTIE arm. No rt-PA administered, and in addition to best medical care.

This includes 14 intent-to-treat patients, and excludes 4 pilots.

Overall Number of Participants Analyzed 42 54 14
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: percentage of participants
2.4
(0.1 to 10.8)
5.6
(1.5 to 13.7)
0
(0 to 19.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Medical Management, MISTIE Surgical Management
Comments Null hypothesis is that rate of symptomatic rebleeding 72 hours post last dose is the same between the two groups. The alternative hypothesis tests whether MISTIE surgical management has a higher rate of symptomatic rebleeding than the medical arm.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.409
Comments [Not Specified]
Method Fisher Exact
Comments One-sided test
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 3.2
Confidence Interval (1-Sided) 95%
9.6
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.9
Estimation Comments MISTIE rate=5.6, 95% upper limit=13.7; medical rate=2.4, 95% upper limit=10.8; comparison considers MISTIE rate minus medical rate
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Medical Management, ICES Surgical Management
Comments Null hypothesis is that rate of symptomatic rebleeding 72 hours post last dose is the same between the two groups. The alternative hypothesis tests whether ICES surgical management has a higher rate of symptomatic rebleeding than the medical arm.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.750
Comments [Not Specified]
Method Fisher Exact
Comments One-sided test
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -2.4
Confidence Interval (1-Sided) 95%
2.2
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.4
Estimation Comments ICES rate=0.0, 95% upper limit=19.3; medical rate=2.4, 95% upper limit=10.8; comparison considers ICES rate minus medical rate
5.Primary Outcome
Title Efficacy Outcome Number 1: Dichotomized Modified Rankin Scale (mRS) at Day 180
Hide Description Percentage of participants with dichotomized mRS score in 0-3 range. The mRS measures the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The scale ranges from 0-6: (0) no symptoms at all, (1) no significant disability despite symptoms; able to carry out all usual duties and activities, (2) slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance, (3) moderate disability; requiring some help, but able to walk without assistance, (4) moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance, (5) severe disability; bedridden, incontinent and requiring constant nursing care and attention, (6) dead
Time Frame 180 days from randomization
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Medical Management MISTIE Surgical Management ICES Surgical Management
Hide Arm/Group Description:
Standard of care medical management as per American Heart Association (AHA) guidelines.

Minimally invasive surgery (MIS) with clot lysis with recombinant tissue plasminogen activator (rt-PA).

MIS+Cathflo Activase (drug): The intervention is a comparison of the safety and preliminary effectiveness of investigational minimally invasive surgery to place a catheter into an intracerebral hemorrhage blood clot and subsequent administration in sequential tiers of 0.3 or 1.0mg of rt-PA, CathFlo® through the catheter once every eight hours for up to 72 hours, in addition to best medical care.

This includes 54 intent-to-treat patients, and excludes 27 pilots.

Intraoperative stereotactic CT-Guided Endoscopic Surgery (ICES)

Mechanical intracerebral hemorrhage removal via an endoscope utilizing the same operative-targeting arm as MISTIE arm. Best medical care was provided, but no rt-PA was administered.

This includes 14 intent-to-treat patients, and excludes 4 pilots.

Overall Number of Participants Analyzed 38 52 14
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: percentage of participants
23.7
(12.9 to 37.7)
34.6
(23.7 to 46.9)
42.9
(20.6 to 67.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Medical Management, MISTIE Surgical Management
Comments Null hypothesis is that the proportion with mRS score of 0-3 at 180 days is the same between the two groups. The alternative hypothesis tests whether MISTIE surgical management has a higher proportion than the medical arm.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.189
Comments [Not Specified]
Method Fisher Exact
Comments One-sided test
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 10.9
Confidence Interval (1-Sided) 95%
26.6
Parameter Dispersion
Type: Standard Error of the mean
Value: 9.5
Estimation Comments MISTIE rate=34.6, 95% upper limit=46.9; medical rate=23.7, 95% upper limit=37.7; comparison considers MISTIE rate minus medical rate.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Medical Management, ICES Surgical Management
Comments Null hypothesis is that the proportion with mRS score of 0-3 at 180 days is the same between the two groups. The alternative hypothesis tests whether ICES surgical management has a higher proportion than the medical arm.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.156
Comments [Not Specified]
Method Fisher Exact
Comments One-sided test
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 19.2
Confidence Interval (1-Sided) 95%
43.7
Parameter Dispersion
Type: Standard Error of the mean
Value: 14.9
Estimation Comments ICES rate=42.9, 95% upper limit=67.5; medical rate=23.7, 95% upper limit=37.7; comparison considers ICES rate minus medical rate.
6.Secondary Outcome
Title Ordinal Modified Rankin Scale (mRS) at Day 180
Hide Description Ordinal distribution of the Modified Rankin Scale score at 180 days. The mRS measures the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The scale ranges from 0-6: (0) no symptoms at all, (1) no significant disability despite symptoms; able to carry out all usual duties and activities, (2) slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance, (3) moderate disability; requiring some help, but able to walk without assistance, (4) moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance, (5) severe disability; bedridden, incontinent and requiring constant nursing care and attention, (6) dead.
Time Frame 180 days from randomization
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Medical Management MISTIE Surgical Management ICES Surgical Management
Hide Arm/Group Description:
Standard of care medical management as per American Heart Association (AHA) guidelines.

Minimally invasive surgery (MIS) with clot lysis with recombinant tissue plasminogen activator (rt-PA).

MIS+Cathflo Activase (drug): The intervention is a comparison of the safety and preliminary effectiveness of investigational minimally invasive surgery to place a catheter into an intracerebral hemorrhage blood clot and subsequent administration in sequential tiers of 0.3 or 1.0mg of rt-PA, CathFlo® through the catheter once every eight hours for up to 72 hours, in addition to best medical care.

This includes 54 intent-to-treat patients, and excludes 27 pilots.

Intraoperative stereotactic CT-Guided Endoscopic Surgery (ICES)

Mechanical intracerebral hemorrhage removal via an endoscope utilizing the same operative-targeting arm as MISTIE arm. Best medical care was provided, but no rt-PA was administered.

This includes 14 intent-to-treat patients, and excludes 4 pilots.

Overall Number of Participants Analyzed 38 52 14
Median (Inter-Quartile Range)
Unit of Measure: units on a scale
4
(4 to 6)
4
(3 to 6)
4
(3 to 5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Medical Management, MISTIE Surgical Management
Comments Null hypothesis is that the distributions of the mRS values for both groups are the same. The alternative hypothesis is that the distributions are not the same.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.468
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments Two-sided test
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Medical Management, ICES Surgical Management
Comments Null hypothesis is that the distributions of the mRS values for both groups are the same. The alternative hypothesis is that the distributions are not the same.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.294
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments Two-sided test
7.Secondary Outcome
Title Ordinal Modified Rankin Scale (mRS) at Day 365
Hide Description Ordinal distribution of the Modified Rankin Scale score at 365 days. The mRS measures the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The scale ranges from 0-6: (0) no symptoms at all, (1) no significant disability despite symptoms; able to carry out all usual duties and activities, (2) slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance, (3) moderate disability; requiring some help, but able to walk without assistance, (4) moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance, (5) severe disability; bedridden, incontinent and requiring constant nursing care and attention, (6) dead.
Time Frame 365 days from randomization
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Medical Management MISTIE Surgical Management ICES Surgical Management
Hide Arm/Group Description:
Standard of care medical management as per American Heart Association (AHA) guidelines.

Minimally invasive surgery (MIS) with clot lysis with recombinant tissue plasminogen activator (rt-PA).

MIS+Cathflo Activase (drug): The intervention is a comparison of the safety and preliminary effectiveness of investigational minimally invasive surgery to place a catheter into an intracerebral hemorrhage blood clot and subsequent administration in sequential tiers of 0.3 or 1.0mg of rt-PA, CathFlo® through the catheter once every eight hours for up to 72 hours, in addition to best medical care.

This includes 54 intent-to-treat patients, and excludes 27 pilots.

Intraoperative stereotactic CT-Guided Endoscopic Surgery (ICES)

Mechanical intracerebral hemorrhage removal via an endoscope utilizing the same operative-targeting arm as MISTIE arm. Best medical care was provided, but no rt-PA was administered.

This includes 14 intent-to-treat patients, and excludes 4 pilots.

Overall Number of Participants Analyzed 24 20 12
Median (Inter-Quartile Range)
Unit of Measure: units on a scale
4.5
(3.5 to 6)
4
(2 to 6)
3.5
(3 to 5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Medical Management, MISTIE Surgical Management
Comments Null hypothesis is that the distributions of the mRS values for both groups are the same. The alternative hypothesis is that the distributions are not the same.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.395
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments Two-sided test
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Medical Management, ICES Surgical Management
Comments Null hypothesis is that the distributions of the mRS values for both groups are the same. The alternative hypothesis is that the distributions are not the same.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.175
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments Two-sided test
8.Secondary Outcome
Title Clot Size Reduction by End of Treatment
Hide Description The percentage of blood clot resolved by the end of treatment CT scan compared to the stability CT scan.
Time Frame Time from randomization until end of treatment, up to 10 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Medical Management MISTIE Surgical Management ICES Surgical Management
Hide Arm/Group Description:
Standard of care medical management as per American Heart Association (AHA) guidelines.

Minimally invasive surgery (MIS) with clot lysis with recombinant tissue plasminogen activator (rt-PA).

MIS+Cathflo Activase (drug): The intervention is a comparison of the safety and preliminary effectiveness of investigational minimally invasive surgery to place a catheter into an intracerebral hemorrhage blood clot and subsequent administration in sequential tiers of 0.3 or 1.0mg of rt-PA, CathFlo® through the catheter once every eight hours for up to 72 hours, in addition to best medical care.

This includes 54 intent-to-treat patients, and excludes 27 pilots.

Intraoperative stereotactic CT-Guided Endoscopic Surgery (ICES)

Mechanical intracerebral hemorrhage removal via an endoscope utilizing the same operative-targeting arm as MISTIE arm. Best medical care was provided, but no rt-PA was administered.

This includes 14 intent-to-treat patients, and excludes 4 pilots.

Overall Number of Participants Analyzed 42 54 14
Median (Inter-Quartile Range)
Unit of Measure: percentage of blood clot resolved
3.9
(-0.06 to 10.2)
64.3
(43.3 to 74.1)
69.5
(59.0 to 86.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Medical Management, MISTIE Surgical Management
Comments Null hypothesis is that the distributions of percentage of blood clot resolved are the same between the two groups. The alternative hypothesis is that the distributions are not the same.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments Two-sided test
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Medical Management, ICES Surgical Management
Comments Null hypothesis is that the distributions of percentage of blood clot resolved are the same between the two groups. The alternative hypothesis is that the distributions are not the same.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments Two-sided test
9.Secondary Outcome
Title Post-operative Clot Size Reduction
Hide Description The percentage of blood clot resolved by the end of treatment CT scan compared to the post-operative CT scan for surgical patients.
Time Frame Time from post-operation until end of treatment, up to 10 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis population only includes surgical patients.
Arm/Group Title Medical Management MISTIE Surgical Management ICES Surgical Management
Hide Arm/Group Description:
Standard of care medical management as per American Heart Association (AHA) guidelines.

Minimally invasive surgery (MIS) with clot lysis with recombinant tissue plasminogen activator (rt-PA).

MIS+Cathflo Activase (drug): The intervention is a comparison of the safety and preliminary effectiveness of investigational minimally invasive surgery to place a catheter into an intracerebral hemorrhage blood clot and subsequent administration in sequential tiers of 0.3 or 1.0mg of rt-PA, CathFlo® through the catheter once every eight hours for up to 72 hours, in addition to best medical care.

This includes 54 intent-to-treat patients, and excludes 27 pilots.

Intraoperative stereotactic CT-Guided Endoscopic Surgery (ICES)

Mechanical intracerebral hemorrhage removal via an endoscope utilizing the same operative-targeting arm as MISTIE arm. Best medical care was provided, but no rt-PA was administered.

This includes 14 intent-to-treat patients, and excludes 4 pilots.

Overall Number of Participants Analyzed 0 54 14
Median (Inter-Quartile Range)
Unit of Measure: percentage of blood clot resolved
56.7
(23.6 to 68.4)
-6.4
(-21.3 to 4.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MISTIE Surgical Management
Comments Null hypothesis is that the median percent resolved is 0. The alternative hypothesis is that the median percent resolved is not equal to 0.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Sign test
Comments Two-sided test
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection ICES Surgical Management
Comments Null hypothesis is that the median percent resolved is 0. The alternative hypothesis is that the median percent resolved is not equal to 0.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.791
Comments [Not Specified]
Method Sign test
Comments Two-sided
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Medical Management MISTIE Surgical Management ICES Surgical Management
Hide Arm/Group Description Standard of care medical management as per American Heart Association (AHA) guidelines.

Minimally invasive surgery (MIS) with clot lysis with recombinant tissue plasminogen activator (rt-PA).

MIS+Cathflo Activase (drug): The intervention is a comparison of the safety and preliminary effectiveness of investigational minimally invasive surgery to place a catheter into an intracerebral hemorrhage blood clot and subsequent administration in sequential tiers of 0.3 or 1.0mg of rt-PA, CathFlo® through the catheter once every eight hours for up to 72 hours, in addition to best medical care.

This includes 54 intent-to-treat patients, and excludes 27 pilots.

Intraoperative stereotactic CT-Guided Endoscopic Surgery

Mechanical intracerebral hemorrhage removal via an endoscope utilizing the same operative-targeting arm as MISTIE arm. Best medical care was provided, but no rt-PA was administered.

This includes 14 intent-to-treat patients, and excludes 4 pilots.

All-Cause Mortality
Medical Management MISTIE Surgical Management ICES Surgical Management
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Medical Management MISTIE Surgical Management ICES Surgical Management
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   23/42 (54.76%)      28/54 (51.85%)      6/14 (42.86%)    
Cardiac disorders       
Cardiac arrest   3/42 (7.14%)  3 1/54 (1.85%)  1 1/14 (7.14%)  1
PVC's, bigemeny   0/42 (0.00%)  0 0/54 (0.00%)  0 1/14 (7.14%)  1
Myocardial infarction   2/42 (4.76%)  2 0/54 (0.00%)  0 0/14 (0.00%)  0
Sinus bradycardia   1/42 (2.38%)  1 0/54 (0.00%)  0 0/14 (0.00%)  0
Gastrointestinal disorders       
Diarrhea   0/42 (0.00%)  0 1/54 (1.85%)  1 1/14 (7.14%)  1
Epistaxis   0/42 (0.00%)  0 1/54 (1.85%)  2 0/14 (0.00%)  0
Duodenal ulcer   1/42 (2.38%)  1 0/54 (0.00%)  0 0/14 (0.00%)  0
Gastric hemorrhage   1/42 (2.38%)  1 0/54 (0.00%)  0 0/14 (0.00%)  0
General disorders       
Death NOS   2/42 (4.76%)  2 1/54 (1.85%)  1 1/14 (7.14%)  1
Sudden death NOS   1/42 (2.38%)  1 0/54 (0.00%)  0 0/14 (0.00%)  0
Infections and infestations       
Bacteremia   0/42 (0.00%)  0 1/54 (1.85%)  1 0/14 (0.00%)  0
Catheter related infection   0/42 (0.00%)  0 1/54 (1.85%)  1 0/14 (0.00%)  0
Lung infection   0/42 (0.00%)  0 1/54 (1.85%)  1 0/14 (0.00%)  0
Endocarditis   0/42 (0.00%)  0 1/54 (1.85%)  1 0/14 (0.00%)  0
Sepsis   1/42 (2.38%)  1 3/54 (5.56%)  5 0/14 (0.00%)  0
Urinary tract infection   0/42 (0.00%)  0 1/54 (1.85%)  1 0/14 (0.00%)  0
Enterocolitis infectious   1/42 (2.38%)  1 0/54 (0.00%)  0 0/14 (0.00%)  0
Upper respiratory infection   1/42 (2.38%)  1 0/54 (0.00%)  0 0/14 (0.00%)  0
Injury, poisoning and procedural complications       
Intraoperative hemorrhage   0/42 (0.00%)  0 1/54 (1.85%)  1 0/14 (0.00%)  0
Pulmonary embolism   1/42 (2.38%)  1 1/54 (1.85%)  1 0/14 (0.00%)  0
Hip fracture   0/42 (0.00%)  0 0/54 (0.00%)  0 1/14 (7.14%)  1
Metabolism and nutrition disorders       
Dehydration   0/42 (0.00%)  0 1/54 (1.85%)  1 0/14 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Left renal mass   0/42 (0.00%)  0 1/54 (1.85%)  1 0/14 (0.00%)  0
Nervous system disorders       
Depressed level of consciousness   0/42 (0.00%)  0 3/54 (5.56%)  3 0/14 (0.00%)  0
Edema cerebral   1/42 (2.38%)  1 1/54 (1.85%)  1 0/14 (0.00%)  0
Intracranial hemorrhage: Tissue, Enlargement   1/42 (2.38%)  1 4/54 (7.41%)  4 0/14 (0.00%)  0
Intracranial hemorrhage: Tissue, New   0/42 (0.00%)  0 2/54 (3.70%)  2 0/14 (0.00%)  0
Intracranial hemorrhage: Ventricular system, New   0/42 (0.00%)  0 1/54 (1.85%)  1 0/14 (0.00%)  0
Intracranial hypertension   4/42 (9.52%)  4 2/54 (3.70%)  3 0/14 (0.00%)  0
Ischemia cerebrovascular   4/42 (9.52%)  4 3/54 (5.56%)  3 0/14 (0.00%)  0
Syncope   1/42 (2.38%)  2 0/54 (0.00%)  0 0/14 (0.00%)  0
Anoxic brain injury   1/42 (2.38%)  1 0/54 (0.00%)  0 0/14 (0.00%)  0
Seizure   2/42 (4.76%)  3 1/54 (1.85%)  1 0/14 (0.00%)  0
Stroke   0/42 (0.00%)  0 1/54 (1.85%)  1 0/14 (0.00%)  0
Cerebrospinal fluid leakage   0/42 (0.00%)  0 0/54 (0.00%)  0 1/14 (7.14%)  1
Intracranial hemorrhage: Catheter Tract, New   0/42 (0.00%)  0 0/54 (0.00%)  0 1/14 (7.14%)  1
Intracranial hemorrhage: Catheter Tract, Enlargement   0/42 (0.00%)  0 0/54 (0.00%)  0 1/14 (7.14%)  1
Intracranial hemorrhage: Ventricular system, Enlargement   1/42 (2.38%)  1 0/54 (0.00%)  0 1/14 (7.14%)  2
Herniation   1/42 (2.38%)  1 0/54 (0.00%)  0 0/14 (0.00%)  0
Hydrocephalus   1/42 (2.38%)  1 0/54 (0.00%)  0 0/14 (0.00%)  0
Somnolence   1/42 (2.38%)  1 0/54 (0.00%)  0 0/14 (0.00%)  0
Renal and urinary disorders       
Acute kidney injury   0/42 (0.00%)  0 1/54 (1.85%)  1 0/14 (0.00%)  0
Urinary retention   0/42 (0.00%)  0 1/54 (1.85%)  1 0/14 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Adult respiratory distress syndrome   2/42 (4.76%)  2 3/54 (5.56%)  3 0/14 (0.00%)  0
Aspiration   1/42 (2.38%)  1 1/54 (1.85%)  1 0/14 (0.00%)  0
Hypoxia   0/42 (0.00%)  0 1/54 (1.85%)  1 0/14 (0.00%)  0
Respiratory arrest   0/42 (0.00%)  0 1/54 (1.85%)  1 0/14 (0.00%)  0
Pneumonitits   1/42 (2.38%)  1 5/54 (9.26%)  5 1/14 (7.14%)  1
Respiratory failure   5/42 (11.90%)  5 6/54 (11.11%)  6 0/14 (0.00%)  0
Ventilatory failure   0/42 (0.00%)  0 1/54 (1.85%)  1 0/14 (0.00%)  0
Vascular disorders       
Hypertension   0/42 (0.00%)  0 2/54 (3.70%)  3 0/14 (0.00%)  0
Hypotension   0/42 (0.00%)  0 1/54 (1.85%)  1 0/14 (0.00%)  0
Thromboembolic event   3/42 (7.14%)  3 0/54 (0.00%)  0 0/14 (0.00%)  0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Medical Management MISTIE Surgical Management ICES Surgical Management
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   24/42 (57.14%)      41/54 (75.93%)      8/14 (57.14%)    
Blood and lymphatic system disorders       
Leukocytosis   1/42 (2.38%)  1 4/54 (7.41%)  4 0/14 (0.00%)  0
Anemia   0/42 (0.00%)  0 8/54 (14.81%)  11 0/14 (0.00%)  0
Cardiac disorders       
Atrial fibrillation   2/42 (4.76%)  2 1/54 (1.85%)  1 0/14 (0.00%)  0
Sinus bradycardia   2/42 (4.76%)  2 0/54 (0.00%)  0 0/14 (0.00%)  0
Gastrointestinal disorders       
Constipation   0/42 (0.00%)  0 5/54 (9.26%)  6 1/14 (7.14%)  1
Diarrhea   0/42 (0.00%)  0 3/54 (5.56%)  3 0/14 (0.00%)  0
General disorders       
Fever   6/42 (14.29%)  6 13/54 (24.07%)  14 3/14 (21.43%)  3
Pain   2/42 (4.76%)  2 2/54 (3.70%)  2 0/14 (0.00%)  0
Localized edema   0/42 (0.00%)  0 3/54 (5.56%)  3 0/14 (0.00%)  0
HCAP   0/42 (0.00%)  0 0/54 (0.00%)  0 1/14 (7.14%)  1
Infections and infestations       
Lung infection   2/42 (4.76%)  3 1/54 (1.85%)  1 1/14 (7.14%)  1
Urinary tract infection   5/42 (11.90%)  6 9/54 (16.67%)  9 0/14 (0.00%)  0
Injury, poisoning and procedural complications       
Fall   0/42 (0.00%)  0 0/54 (0.00%)  0 1/14 (7.14%)  1
Metabolism and nutrition disorders       
Hyperglycemia   1/42 (2.38%)  1 4/54 (7.41%)  4 0/14 (0.00%)  0
Hypocalcemia   2/42 (4.76%)  2 4/54 (7.41%)  4 0/14 (0.00%)  0
Hypoglycemia   2/42 (4.76%)  3 1/54 (1.85%)  1 0/14 (0.00%)  0
Hypokalemia   1/42 (2.38%)  1 6/54 (11.11%)  6 0/14 (0.00%)  0
Hypomagnesemia   1/42 (2.38%)  1 3/54 (5.56%)  3 0/14 (0.00%)  0
Hyponatremia   1/42 (2.38%)  1 4/54 (7.41%)  4 0/14 (0.00%)  0
Hyperkalemia   0/42 (0.00%)  0 3/54 (5.56%)  3 0/14 (0.00%)  0
Hypernatremia   0/42 (0.00%)  0 4/54 (7.41%)  4 0/14 (0.00%)  0
Hypophosphatemia   0/42 (0.00%)  0 4/54 (7.41%)  4 0/14 (0.00%)  0
Nervous system disorders       
Seizure   3/42 (7.14%)  5 4/54 (7.41%)  4 0/14 (0.00%)  0
Intracranial hemorrhage: Catheter Tract, Enlargement   0/42 (0.00%)  0 3/54 (5.56%)  4 0/14 (0.00%)  0
Intracranial hemorrhage: Catheter Tract, New   0/42 (0.00%)  0 6/54 (11.11%)  6 0/14 (0.00%)  0
Intracranial hemorrhage: Tissue, Enlargement   0/42 (0.00%)  0 3/54 (5.56%)  4 0/14 (0.00%)  0
Intracranial hemorrhage: Ventricular system, Enlargement   0/42 (0.00%)  0 3/54 (5.56%)  3 0/14 (0.00%)  0
Wound reclosure after serious fluid leak   0/42 (0.00%)  0 0/54 (0.00%)  0 1/14 (7.14%)  1
Renal and urinary disorders       
Acute renal failure   1/42 (2.38%)  1 3/54 (5.56%)  3 0/14 (0.00%)  0
Hematuria   2/42 (4.76%)  2 1/54 (1.85%)  1 0/14 (0.00%)  0
Urinary retention   1/42 (2.38%)  1 3/54 (5.56%)  3 0/14 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Aspiration   5/42 (11.90%)  5 1/54 (1.85%)  1 0/14 (0.00%)  0
Atelectasis   1/42 (2.38%)  1 3/54 (5.56%)  3 0/14 (0.00%)  0
Pneumonitis   7/42 (16.67%)  7 6/54 (11.11%)  6 2/14 (14.29%)  2
Ventilatory failure   1/42 (2.38%)  1 3/54 (5.56%)  3 0/14 (0.00%)  0
Pleural effusion   0/42 (0.00%)  0 5/54 (9.26%)  5 0/14 (0.00%)  0
Vascular disorders       
Hypertension   4/42 (9.52%)  4 6/54 (11.11%)  6 0/14 (0.00%)  0
Thromboembolic event   1/42 (2.38%)  1 5/54 (9.26%)  5 0/14 (0.00%)  0
Hypotension   0/42 (0.00%)  0 3/54 (5.56%)  5 0/14 (0.00%)  0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
The only disclosure restriction on the PI is that the funding agency (NIH/NINDS) can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days from the time submitted to the funding agency for review. The funding agency cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
Name/Title: Dr. Daniel F. Hanley
Organization: Johns Hopkins University
Phone: (410) 614-6996
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Daniel Hanley, Johns Hopkins University
ClinicalTrials.gov Identifier: NCT00224770     History of Changes
Other Study ID Numbers: ICH01
R01NS046309 ( U.S. NIH Grant/Contract )
First Submitted: September 21, 2005
First Posted: September 23, 2005
Results First Submitted: September 21, 2014
Results First Posted: June 18, 2015
Last Update Posted: June 18, 2015