MISTIE: Minimally Invasive Surgery and rtPA for Intracerebral Hemorrhage Evacuation

• Sponsor: Daniel Hanley (Other)
• Overall Status: Completed
• CT.gov ID: NCT00224770
• Collaborator: National Institute of Neurological Disorders and Stroke (NINDS) (NIH), Genentech, Inc. (Industry), Emissary International LLC (Industry)
• Enrollment: 141
• Locations: 29
• Arms: 3
• Duration (Months): 92
• Patients Per Site: 4.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this trial is to determine the safety of using a combination of minimally invasive surgery and clot lysis with rt-PA to remove intracerebral hemorrhage (ICH). The ICES arm of the trial will determine the safety of endoscopic surgery to remove ICH. All MISTIE intention to treat subjects represent the hypothesized test group. The ICES cohort is to be analyzed separately.

Condition or Disease	Intervention/Treatment	Phase
Intracerebral Hemorrhage	Drug: MIS+Cathflo Activase (drug); Procedure: Intraoperative stereotactic CT-Guided Endoscopic Surgery	Phase 2

Detailed Description

The purpose of this trial is to determine the safety of using a combination of minimally invasive surgery and clot lysis with rt-PA to remove intracerebral hemorrhage (ICH). The procedure is to use image-based surgery (MRI or CT) to provide catheter access to ICH for the intervention, which is a one-time clot aspiration followed by instillation of rt-PA over 72 hours.

The Intraoperative stereotactic CT-guided Endoscopic Surgery (ICES) arm of the trial will determine the safety, feasibility and effectiveness of endoscopic surgery to remove ICH. This tests the first step of the MISTIE surgical procedure with an endoscope, not a rigid cannula.

We propose to test if these interventions facilitate more rapid and complete recovery of function and decreased mortality from this condition compared to conventional medical management without subjecting the patient to craniotomy. The specific objective of this trial is to test the safety of these interventions and assess their ability to remove blood clot from brain tissue.

Study Design

• Study Type: Interventional
• Actual Enrollment: 141 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Minimally Invasive Surgery and rtPA for Intracerebral Hemorrhage Evacuation
• Study Start Date: Aug 1, 2005
• Actual Primary Completion Date: Aug 1, 2012
• Actual Study Completion Date: Apr 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Medical Management Standard of care medical management as per American Heart Association (AHA) guidelines.
Active Comparator: MISTIE Surgical Management 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.	Drug: MIS+Cathflo Activase (drug); 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.; Other Names: rtPA
Active Comparator: ICES Surgical Management 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.	Procedure: Intraoperative stereotactic CT-Guided Endoscopic Surgery; Mechanical intracerebral hemorrhage removal via an endoscope utilizing the same operative targeting arm as MISTIE arm. No rt-PA administered, and in addition to best medical care.

Outcome Measures

Primary Outcome Measures

1. Safety Outcome Number 1: Rate of Mortality [30 days from randomization]

   Percentage of participants who died during the first 30 days after randomization.

2. Safety Outcome Number 2: Rate of Procedure-related Mortality [7 days from randomization]

   Percentage of participants who died during the first 7 days after randomization.

3. Safety Outcome Number 3: Rate of Cerebritis, Meningitis, Bacterial Ventriculitis [30 days from randomization]

   Percentage of participants who had a bacterial brain infection (cerebritis, meningitis, ventriculitis) within 30 days of randomization.

4. Safety Outcome Number 4: Rate of Symptomatic Rebleeding [72 hours post last dose]

   The difference in the rate of symptomatic rebleeding 72 hours post last dose.

5. Efficacy Outcome Number 1: Dichotomized Modified Rankin Scale (mRS) at Day 180 [180 days from randomization]

   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

Secondary Outcome Measures

1. Ordinal Modified Rankin Scale (mRS) at Day 180 [180 days from randomization]

   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.

2. Ordinal Modified Rankin Scale (mRS) at Day 365 [365 days from randomization]

   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.

3. Clot Size Reduction by End of Treatment [Time from randomization until end of treatment, up to 10 days]

   The percentage of blood clot resolved by the end of treatment CT scan compared to the stability CT scan.

4. Post-operative Clot Size Reduction [Time from post-operation until end of treatment, up to 10 days]

   The percentage of blood clot resolved by the end of treatment CT scan compared to the post-operative CT scan for surgical patients.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age 18-80

• GCS < 14 or a NIHSS > or equal to 6

• Spontaneous supratentorial ICH > or equal to 20cc

• Symptoms less than 12 hours prior to diagnostic CT scan (an unknown time of symptom onset is exclusionary)

• Intention to initiate surgery within 48 hours after diagnostic CT

• First dose can be given within 54 hours after diagnostic CT (delays for post surgical stabilization of catheter bleeding or because of unanticipated surgical delay are acceptable with approved waiver from the coordinating center) (Does not apply to ICES Tier)

• Six-hour clot size equal to the most previous clot size + 5 cc (as determined by an additional CT scan at least 6 hours after the initial stability scan (ABC)/2 method)

• SBP < 200 mmHg sustained for 6 hours recorded closest to time of randomization

• Historical Rankin score of 0 or 1

• Negative pregnancy test

Exclusion Criteria:

• Infratentorial hemorrhage (any involvement of the midbrain or lower brainstem as demonstrated by radiograph or complete third nerve palsy)

• Patients with platelet count < 100,000, INR > 1.4, or an elevated PT or APTT (reversal of coumadin is permitted but the patient must not require coumadin during the acute hospitalization). Irreversible coagulopathy either due to medical condition or prior to randomization

• Clotting disorders

• Any concurrent serious illness that would interfere with the safety assessments including hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, immunologic, and hematologic disease

• Patients with a mechanical valve

• Patients with unstable mass or evolving intracranial compartment syndrome

• Ruptured aneurysm, AVM, vascular anomaly

• Greater than 80 years (higher incidence of amyloid)

• Under 18 years of ag e (high incidence of occult vascular malformation)

• Pregnant (positive pregnancy test) or lactating females (likelihood of altered coagulation function associated with the high estrogen/progesterone state)

• Irreversibly impaired brainstem function (bilateral fixed, dilated pupils and extensor motor posturing), GCS less than or equal to 4

• Historical Rankin score greater than or equal to 2

• Intraventricular hemorrhage requiring external ventricular drainage

• Internal bleeding, involving retroperitoneal sites, or the gastrointestinal, genitourinary, or respiratory tracts (Does not apply to ICES Tier)

• Superficial or surface bleeding, observed mainly at vascular puncture and access sites (e.g., venous cutdowns, arterial punctures) or site of recent surgical intervention (Does not apply to ICES Tier)

• Known risk for embolization, including history of left heart thrombus, mitral stenosis with atrial fibrillation, acute pericarditis, and subacute bacterial endocarditis (Does not apply to ICES Tier)

• In the investigator's opinion, the patient is unstable and would benefit from a specific intervention rather than supportive care plus or minus MIS+rtPA

• Prior enrollment in the study

• Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated

• Participation in another simultaneous trial of ICH treatment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	Barrow Neurosurgical Associates	Phoenix	Arizona	United States	85013
3	University of California Los Angeles	Los Angeles	California	United States	90095
4	Stanford University	Palo Alto	California	United States	94034
5	University of California, San Diego	San Diego	California	United States	92103
6	Hartford Hospital	Hartford	Connecticut	United States	06102
7	Georgetown University	Washington	District of Columbia	United States	20007
8	Mayo Clinic	Jacksonville	Florida	United States	32216
9	Rush University	Chicago	Illinois	United States	60612
10	University of Chicago	Chicago	Illinois	United States	60637
11	NorthShore University Health System	Evanston	Illinois	United States	60201
12	University of Maryland Medical Systems	Baltimore	Maryland	United States	21201
13	Johns Hopkins University/Bayview Medical Center	Baltimore	Maryland	United States	21287
14	Henry Ford Health System	Detroit	Michigan	United States	48202
15	JFK Medical Center New Jersey	Edison	New Jersey	United States	08818
16	Mt. Sinai Medical Center	New York	New York	United States	10029
17	University of Cincinnati	Cincinnati	Ohio	United States	45267
18	Case Western University	Cleveland	Ohio	United States	44106
19	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
20	Temple University	Philadelphia	Pennsylvania	United States	19140
21	Allegheny General Hospital	Pittsburgh	Pennsylvania	United States	15212
22	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15213
23	Medical University of South Carolina	Charleston	South Carolina	United States	29425
24	University of Texas, Houston	Houston	Texas	United States	77030
25	University of Texas HSC, San Antonio	San Antonio	Texas	United States	78229
26	Virginia Commonwealth University	Richmond	Virginia	United States	23298
27	Montreal Neurological Institute at McGill University	Montreal	Quebec	Canada	H3A 2B4
28	University of Heidelberg	Heidelberg		Germany	69117
29	Newcastle General Hospital	Newcastle		United Kingdom

Sponsors and Collaborators

• Daniel Hanley
• National Institute of Neurological Disorders and Stroke (NINDS)
• Genentech, Inc.
• Emissary International LLC

Investigators

• Study Chair: Daniel F. Hanley, MD, Johns Hopkins University
• Principal Investigator: Mario Zuccarello, MD, University of Cincinnati
• Principal Investigator: Paul Vespa, MD, University of California, Los Angeles

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Trial website

Publications

None provided.

• Responsible Party: Daniel Hanley, MD, Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT00224770
• Other Study ID Numbers: ICH01; R01NS046309
• First Posted: Sep 23, 2005
• Last Update Posted: Jun 18, 2015
• Last Verified: Jun 1, 2015

• Additional relevant MeSH terms: Cerebral Hemorrhage; Hemorrhage; Tissue Plasminogen Activator

Study Results

Participant Flow

Recruitment Details	110 patients were randomized to the trial, and 31 were recruited as pilot patients.
Pre-assignment Detail	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
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

Baseline Characteristics

Arm/Group Title	Medical Management	MISTIE Surgical Management	ICES Surgical Management	Total
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 Participants	42	54	14	110
Age (Count of Participants)
<=18 years	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 (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	62	60	59	61
Sex: Female, Male (Count of 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 (participants) [Number]
United States	41 97.6%	53 98.1%	14 100%	108 98.2%
United Kingdom	1 2.4%	1 1.9%	0 0%	2 1.8%

Outcome Measures

1. Primary Outcome

Title	Safety Outcome Number 1: Rate of Mortality
Description	Percentage of participants who died during the first 30 days after randomization.
Time Frame	30 days from randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Medical Management	MISTIE Surgical Management	ICES Surgical Management
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.
Measure Participants	42	54	14
Number (90% Confidence Interval) [percentage of participants]	9.5 22.6%	14.8 27.4%	7.1 50.7%

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
Statistical Test of Hypothesis	p-Value	0.324
	Comments
	Method	Fisher Exact
	Comments	One-sided test
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	5.3
	Confidence Interval	(1-Sided) 95%; to 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.

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
Statistical Test of Hypothesis	p-Value	0.633
	Comments
	Method	Fisher Exact
	Comments	One-sided test
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-2.4
	Confidence Interval	(1-Sided) 95%; to 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
Description	Percentage of participants who died during the first 7 days after randomization.
Time Frame	7 days from randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Medical Management	MISTIE Surgical Management	ICES Surgical Management
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.
Measure Participants	42	54	14
Number (90% Confidence Interval) [percentage of participants]	0 0%	5.6 10.4%	0 0%

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
Statistical Test of Hypothesis	p-Value	0.174
	Comments
	Method	Fisher Exact
	Comments	One-sided test
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	5.6
	Confidence Interval	(1-Sided) 95%; to 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
Description	Percentage of participants who had a bacterial brain infection (cerebritis, meningitis, ventriculitis) within 30 days of randomization.
Time Frame	30 days from randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Medical Management	MISTIE Surgical Management	ICES Surgical Management
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.
Measure Participants	42	54	14
Number (90% Confidence Interval) [percentage of participants]	2.4 5.7%	0 0%	0 0%

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
Statistical Test of Hypothesis	p-Value	0.437
	Comments
	Method	Fisher Exact
	Comments	One-sided test
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-2.4
	Confidence Interval	(1-Sided) 95%; to 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.

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
Statistical Test of Hypothesis	p-Value	0.750
	Comments
	Method	Fisher Exact
	Comments	One-sided test
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-2.4
	Confidence Interval	(1-Sided) 95%; to 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
Description	The difference in the rate of symptomatic rebleeding 72 hours post last dose.
Time Frame	72 hours post last dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Medical Management	MISTIE Surgical Management	ICES Surgical Management
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.
Measure Participants	42	54	14
Number (90% Confidence Interval) [percentage of participants]	2.4 5.7%	5.6 10.4%	0 0%

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
Statistical Test of Hypothesis	p-Value	0.409
	Comments
	Method	Fisher Exact
	Comments	One-sided test
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	3.2
	Confidence Interval	(1-Sided) 95%; to 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

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
Statistical Test of Hypothesis	p-Value	0.750
	Comments
	Method	Fisher Exact
	Comments	One-sided test
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-2.4
	Confidence Interval	(1-Sided) 95%; to 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. Secondary Outcome

Title	Ordinal Modified Rankin Scale (mRS) at Day 180
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Medical Management	MISTIE Surgical Management	ICES Surgical Management
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.
Measure Participants	38	52	14
Median (Inter-Quartile Range) [units on a scale]	4	4	4

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
Statistical Test of Hypothesis	p-Value	0.468
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	Two-sided test

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
Statistical Test of Hypothesis	p-Value	0.294
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	Two-sided test

6. Secondary Outcome

Title	Ordinal Modified Rankin Scale (mRS) at Day 365
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Medical Management	MISTIE Surgical Management	ICES Surgical Management
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.
Measure Participants	24	20	12
Median (Inter-Quartile Range) [units on a scale]	4.5	4	3.5

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
Statistical Test of Hypothesis	p-Value	0.395
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	Two-sided test

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
Statistical Test of Hypothesis	p-Value	0.175
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	Two-sided test

7. Secondary Outcome

Title	Clot Size Reduction by End of Treatment
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Medical Management	MISTIE Surgical Management	ICES Surgical Management
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.
Measure Participants	42	54	14
Median (Inter-Quartile Range) [percentage of blood clot resolved]	3.9	64.3	69.5

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
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	Two-sided test

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
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	Two-sided test

8. Secondary Outcome

Title	Post-operative Clot Size Reduction
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

Outcome Measure Data

Analysis Population Description

Analysis population only includes surgical patients.

Arm/Group Title	Medical Management	MISTIE Surgical Management	ICES Surgical Management
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.
Measure Participants	0	54	14
Median (Inter-Quartile Range) [percentage of blood clot resolved]	56.7	-6.4

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
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Sign test
	Comments	Two-sided test

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
Statistical Test of Hypothesis	p-Value	0.791
	Comments
	Method	Sign test
	Comments	Two-sided

9. Primary Outcome

Title	Efficacy Outcome Number 1: Dichotomized Modified Rankin Scale (mRS) at Day 180
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Medical Management	MISTIE Surgical Management	ICES Surgical Management
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.
Measure Participants	38	52	14
Number (90% Confidence Interval) [percentage of participants]	23.7 56.4%	34.6 64.1%	42.9 306.4%

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
Statistical Test of Hypothesis	p-Value	0.189
	Comments
	Method	Fisher Exact
	Comments	One-sided test
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	10.9
	Confidence Interval	(1-Sided) 95%; to 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.

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
Statistical Test of Hypothesis	p-Value	0.156
	Comments
	Method	Fisher Exact
	Comments	One-sided test
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	19.2
	Confidence Interval	(1-Sided) 95%; to 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.

Adverse Events

Arm/Group Title	Medical Management		MISTIE Surgical Management		ICES Surgical Management
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 (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
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 (54.8%)		28/54 (51.9%)		6/14 (42.9%)
Cardiac disorders
Cardiac arrest	3/42 (7.1%)	3	1/54 (1.9%)	1	1/14 (7.1%)	1
PVC's, bigemeny	0/42 (0%)	0	0/54 (0%)	0	1/14 (7.1%)	1
Myocardial infarction	2/42 (4.8%)	2	0/54 (0%)	0	0/14 (0%)	0
Sinus bradycardia	1/42 (2.4%)	1	0/54 (0%)	0	0/14 (0%)	0
Gastrointestinal disorders
Diarrhea	0/42 (0%)	0	1/54 (1.9%)	1	1/14 (7.1%)	1
Epistaxis	0/42 (0%)	0	1/54 (1.9%)	2	0/14 (0%)	0
Duodenal ulcer	1/42 (2.4%)	1	0/54 (0%)	0	0/14 (0%)	0
Gastric hemorrhage	1/42 (2.4%)	1	0/54 (0%)	0	0/14 (0%)	0
General disorders
Death NOS	2/42 (4.8%)	2	1/54 (1.9%)	1	1/14 (7.1%)	1
Sudden death NOS	1/42 (2.4%)	1	0/54 (0%)	0	0/14 (0%)	0
Infections and infestations
Bacteremia	0/42 (0%)	0	1/54 (1.9%)	1	0/14 (0%)	0
Catheter related infection	0/42 (0%)	0	1/54 (1.9%)	1	0/14 (0%)	0
Lung infection	0/42 (0%)	0	1/54 (1.9%)	1	0/14 (0%)	0
Endocarditis	0/42 (0%)	0	1/54 (1.9%)	1	0/14 (0%)	0
Sepsis	1/42 (2.4%)	1	3/54 (5.6%)	5	0/14 (0%)	0
Urinary tract infection	0/42 (0%)	0	1/54 (1.9%)	1	0/14 (0%)	0
Enterocolitis infectious	1/42 (2.4%)	1	0/54 (0%)	0	0/14 (0%)	0
Upper respiratory infection	1/42 (2.4%)	1	0/54 (0%)	0	0/14 (0%)	0
Injury, poisoning and procedural complications
Intraoperative hemorrhage	0/42 (0%)	0	1/54 (1.9%)	1	0/14 (0%)	0
Pulmonary embolism	1/42 (2.4%)	1	1/54 (1.9%)	1	0/14 (0%)	0
Hip fracture	0/42 (0%)	0	0/54 (0%)	0	1/14 (7.1%)	1
Metabolism and nutrition disorders
Dehydration	0/42 (0%)	0	1/54 (1.9%)	1	0/14 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Left renal mass	0/42 (0%)	0	1/54 (1.9%)	1	0/14 (0%)	0
Nervous system disorders
Depressed level of consciousness	0/42 (0%)	0	3/54 (5.6%)	3	0/14 (0%)	0
Edema cerebral	1/42 (2.4%)	1	1/54 (1.9%)	1	0/14 (0%)	0
Intracranial hemorrhage: Tissue, Enlargement	1/42 (2.4%)	1	4/54 (7.4%)	4	0/14 (0%)	0
Intracranial hemorrhage: Tissue, New	0/42 (0%)	0	2/54 (3.7%)	2	0/14 (0%)	0
Intracranial hemorrhage: Ventricular system, New	0/42 (0%)	0	1/54 (1.9%)	1	0/14 (0%)	0
Intracranial hypertension	4/42 (9.5%)	4	2/54 (3.7%)	3	0/14 (0%)	0
Ischemia cerebrovascular	4/42 (9.5%)	4	3/54 (5.6%)	3	0/14 (0%)	0
Syncope	1/42 (2.4%)	2	0/54 (0%)	0	0/14 (0%)	0
Anoxic brain injury	1/42 (2.4%)	1	0/54 (0%)	0	0/14 (0%)	0
Seizure	2/42 (4.8%)	3	1/54 (1.9%)	1	0/14 (0%)	0
Stroke	0/42 (0%)	0	1/54 (1.9%)	1	0/14 (0%)	0
Cerebrospinal fluid leakage	0/42 (0%)	0	0/54 (0%)	0	1/14 (7.1%)	1
Intracranial hemorrhage: Catheter Tract, New	0/42 (0%)	0	0/54 (0%)	0	1/14 (7.1%)	1
Intracranial hemorrhage: Catheter Tract, Enlargement	0/42 (0%)	0	0/54 (0%)	0	1/14 (7.1%)	1
Intracranial hemorrhage: Ventricular system, Enlargement	1/42 (2.4%)	1	0/54 (0%)	0	1/14 (7.1%)	2
Herniation	1/42 (2.4%)	1	0/54 (0%)	0	0/14 (0%)	0
Hydrocephalus	1/42 (2.4%)	1	0/54 (0%)	0	0/14 (0%)	0
Somnolence	1/42 (2.4%)	1	0/54 (0%)	0	0/14 (0%)	0
Renal and urinary disorders
Acute kidney injury	0/42 (0%)	0	1/54 (1.9%)	1	0/14 (0%)	0
Urinary retention	0/42 (0%)	0	1/54 (1.9%)	1	0/14 (0%)	0
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome	2/42 (4.8%)	2	3/54 (5.6%)	3	0/14 (0%)	0
Aspiration	1/42 (2.4%)	1	1/54 (1.9%)	1	0/14 (0%)	0
Hypoxia	0/42 (0%)	0	1/54 (1.9%)	1	0/14 (0%)	0
Respiratory arrest	0/42 (0%)	0	1/54 (1.9%)	1	0/14 (0%)	0
Pneumonitits	1/42 (2.4%)	1	5/54 (9.3%)	5	1/14 (7.1%)	1
Respiratory failure	5/42 (11.9%)	5	6/54 (11.1%)	6	0/14 (0%)	0
Ventilatory failure	0/42 (0%)	0	1/54 (1.9%)	1	0/14 (0%)	0
Vascular disorders
Hypertension	0/42 (0%)	0	2/54 (3.7%)	3	0/14 (0%)	0
Hypotension	0/42 (0%)	0	1/54 (1.9%)	1	0/14 (0%)	0
Thromboembolic event	3/42 (7.1%)	3	0/54 (0%)	0	0/14 (0%)	0
Other (Not Including Serious) Adverse Events
	Medical Management		MISTIE Surgical Management		ICES Surgical Management
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/42 (57.1%)		41/54 (75.9%)		8/14 (57.1%)
Blood and lymphatic system disorders
Leukocytosis	1/42 (2.4%)	1	4/54 (7.4%)	4	0/14 (0%)	0
Anemia	0/42 (0%)	0	8/54 (14.8%)	11	0/14 (0%)	0
Cardiac disorders
Atrial fibrillation	2/42 (4.8%)	2	1/54 (1.9%)	1	0/14 (0%)	0
Sinus bradycardia	2/42 (4.8%)	2	0/54 (0%)	0	0/14 (0%)	0
Gastrointestinal disorders
Constipation	0/42 (0%)	0	5/54 (9.3%)	6	1/14 (7.1%)	1
Diarrhea	0/42 (0%)	0	3/54 (5.6%)	3	0/14 (0%)	0
General disorders
Fever	6/42 (14.3%)	6	13/54 (24.1%)	14	3/14 (21.4%)	3
Pain	2/42 (4.8%)	2	2/54 (3.7%)	2	0/14 (0%)	0
Localized edema	0/42 (0%)	0	3/54 (5.6%)	3	0/14 (0%)	0
HCAP	0/42 (0%)	0	0/54 (0%)	0	1/14 (7.1%)	1
Infections and infestations
Lung infection	2/42 (4.8%)	3	1/54 (1.9%)	1	1/14 (7.1%)	1
Urinary tract infection	5/42 (11.9%)	6	9/54 (16.7%)	9	0/14 (0%)	0
Injury, poisoning and procedural complications
Fall	0/42 (0%)	0	0/54 (0%)	0	1/14 (7.1%)	1
Metabolism and nutrition disorders
Hyperglycemia	1/42 (2.4%)	1	4/54 (7.4%)	4	0/14 (0%)	0
Hypocalcemia	2/42 (4.8%)	2	4/54 (7.4%)	4	0/14 (0%)	0
Hypoglycemia	2/42 (4.8%)	3	1/54 (1.9%)	1	0/14 (0%)	0
Hypokalemia	1/42 (2.4%)	1	6/54 (11.1%)	6	0/14 (0%)	0
Hypomagnesemia	1/42 (2.4%)	1	3/54 (5.6%)	3	0/14 (0%)	0
Hyponatremia	1/42 (2.4%)	1	4/54 (7.4%)	4	0/14 (0%)	0
Hyperkalemia	0/42 (0%)	0	3/54 (5.6%)	3	0/14 (0%)	0
Hypernatremia	0/42 (0%)	0	4/54 (7.4%)	4	0/14 (0%)	0
Hypophosphatemia	0/42 (0%)	0	4/54 (7.4%)	4	0/14 (0%)	0
Nervous system disorders
Seizure	3/42 (7.1%)	5	4/54 (7.4%)	4	0/14 (0%)	0
Intracranial hemorrhage: Catheter Tract, Enlargement	0/42 (0%)	0	3/54 (5.6%)	4	0/14 (0%)	0
Intracranial hemorrhage: Catheter Tract, New	0/42 (0%)	0	6/54 (11.1%)	6	0/14 (0%)	0
Intracranial hemorrhage: Tissue, Enlargement	0/42 (0%)	0	3/54 (5.6%)	4	0/14 (0%)	0
Intracranial hemorrhage: Ventricular system, Enlargement	0/42 (0%)	0	3/54 (5.6%)	3	0/14 (0%)	0
Wound reclosure after serious fluid leak	0/42 (0%)	0	0/54 (0%)	0	1/14 (7.1%)	1
Renal and urinary disorders
Acute renal failure	1/42 (2.4%)	1	3/54 (5.6%)	3	0/14 (0%)	0
Hematuria	2/42 (4.8%)	2	1/54 (1.9%)	1	0/14 (0%)	0
Urinary retention	1/42 (2.4%)	1	3/54 (5.6%)	3	0/14 (0%)	0
Respiratory, thoracic and mediastinal disorders
Aspiration	5/42 (11.9%)	5	1/54 (1.9%)	1	0/14 (0%)	0
Atelectasis	1/42 (2.4%)	1	3/54 (5.6%)	3	0/14 (0%)	0
Pneumonitis	7/42 (16.7%)	7	6/54 (11.1%)	6	2/14 (14.3%)	2
Ventilatory failure	1/42 (2.4%)	1	3/54 (5.6%)	3	0/14 (0%)	0
Pleural effusion	0/42 (0%)	0	5/54 (9.3%)	5	0/14 (0%)	0
Vascular disorders
Hypertension	4/42 (9.5%)	4	6/54 (11.1%)	6	0/14 (0%)	0
Thromboembolic event	1/42 (2.4%)	1	5/54 (9.3%)	5	0/14 (0%)	0
Hypotension	0/42 (0%)	0	3/54 (5.6%)	5	0/14 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.