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

This study has been completed.

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

ClinicalTrials.gov Identifier:

NCT00224770

First received: September 21, 2005

Last updated: June 17, 2015

Last verified: June 2015

History of Changes

Results First Received: September 21, 2014

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

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
110 patients were randomized to the trial, and 31 were recruited as pilot patients.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups

Description

Medical Management

Standard of care medical management as per American Heart Association (AHA) guidelines.

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.

ICES Surgical Management

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.

Participant Flow: Overall Study

	Medical Management	MISTIE Surgical Management	ICES Surgical Management
STARTED	42	54	14
COMPLETED	38	52	14
NOT COMPLETED	4	2	0
Lost to Follow-up	4	2	0

Baseline Characteristics

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Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The decision was made to exclude the pilot patients from the analysis...

Reporting Groups

	Description
Medical Management	Standard of care medical management as per American Heart Association (AHA) guidelines.
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.
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.
Total	Total of all reporting groups

Baseline Measures

	Medical Management	MISTIE Surgical Management	ICES Surgical Management	Total
Overall Participants Analyzed [Units: Participants]	42	54	14	110

Age [Units: Participants]
<=18 years	0	0	0	0
Between 18 and 65 years	18	25	9	52
>=65 years	24	29	5	58

Age [Units: Years] Median (Inter-Quartile Range)	62 (49.5 to 73)	60 (54 to 69)	59 (53.2 to 68.2)	61 (53.3 to 70)

Gender [Units: Participants]
Female	14	19	5	38
Male	28	35	9	72

Region of Enrollment [Units: Participants]
United States	41	53	14	108
United Kingdom	1	1	0	2

Outcome Measures

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1. Primary:

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

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2. Primary:

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

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3. Primary:

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

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4. Primary:

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

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5. Primary:

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

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6. Secondary:

Ordinal Modified Rankin Scale (mRS) at Day 180 [ Time Frame: 180 days from randomization ]

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7. Secondary:

Ordinal Modified Rankin Scale (mRS) at Day 365 [ Time Frame: 365 days from randomization ]

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8. Secondary:

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

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9. Secondary:

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

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Serious Adverse Events

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Other Adverse Events

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Limitations and Caveats

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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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More Information

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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 agreement is:

	The only disclosure restriction on the PI is that the sponsor 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. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: 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
e-mail: dhanley@jhmi.edu

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Vespa P, Hanley D, Betz J, Hoffer A, Engh J, Carter R, Nakaji P, Ogilvy C, Jallo J, Selman W, Bistran-Hall A, Lane K, McBee N, Saver J, Thompson RE, Martin N; ICES Investigators. ICES (Intraoperative Stereotactic Computed Tomography-Guided Endoscopic Surgery) for Brain Hemorrhage: A Multicenter Randomized Controlled Trial. Stroke. 2016 Nov;47(11):2749-2755. Epub 2016 Oct 6.

Hanley DF, Thompson RE, Muschelli J, Rosenblum M, McBee N, Lane K, Bistran-Hall AJ, Mayo SW, Keyl P, Gandhi D, Morgan TC, Ullman N, Mould WA, Carhuapoma JR, Kase C, Ziai W, Thompson CB, Yenokyan G, Huang E, Broaddus WC, Graham RS, Aldrich EF, Dodd R, Wijman C, Caron JL, Huang J, Camarata P, Mendelow AD, Gregson B, Janis S, Vespa P, Martin N, Awad I, Zuccarello M; MISTIE Investigators. Safety and efficacy of minimally invasive surgery plus alteplase in intracerebral haemorrhage evacuation (MISTIE): a randomised, controlled, open-label, phase 2 trial. Lancet Neurol. 2016 Nov;15(12):1228-1237. doi: 10.1016/S1474-4422(16)30234-4. Epub 2016 Oct 11.

Muschelli J, Ullman NL, Sweeney EM, Eloyan A, Martin N, Vespa P, Hanley DF, Crainiceanu CM. Quantitative Intracerebral Hemorrhage Localization. Stroke. 2015 Nov;46(11):3270-3. doi: 10.1161/STROKEAHA.115.010369. Epub 2015 Oct 8.

Webb AJ, Ullman NL, Morgan TC, Muschelli J, Kornbluth J, Awad IA, Mayo S, Rosenblum M, Ziai W, Zuccarrello M, Aldrich F, John S, Harnof S, Lopez G, Broaddus WC, Wijman C, Vespa P, Bullock R, Haines SJ, Cruz-Flores S, Tuhrim S, Hill MD, Narayan R, Hanley DF; MISTIE and CLEAR Investigators. Accuracy of the ABC/2 Score for Intracerebral Hemorrhage: Systematic Review and Analysis of MISTIE, CLEAR-IVH, and CLEAR III. Stroke. 2015 Sep;46(9):2470-6. doi: 10.1161/STROKEAHA.114.007343. Epub 2015 Aug 4. Review.

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 )
Study First Received:	September 21, 2005
Results First Received:	September 21, 2014
Last Updated:	June 17, 2015

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