Minimally Invasive Surgery and rtPA for Intracerebral Hemorrhage Evacuation

NCT ID: NCT00224770

Last Updated: 2015-06-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 141 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-08-31
• Study Completion Date: 2013-04-30

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.

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.

Conditions

Intracerebral Hemorrhage

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Medical Management

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

Group Type: NO_INTERVENTION

No interventions assigned to this group

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.

Group Type: ACTIVE_COMPARATOR

MIS+Cathflo Activase (drug)

Intervention Type: 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.

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.

Group Type: ACTIVE_COMPARATOR

Intraoperative stereotactic CT-Guided Endoscopic Surgery

Intervention Type: PROCEDURE

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: PROCEDURE

Other Intervention Names

rtPA

Eligibility Criteria

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 (A*B*C)/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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

Emissary International LLC

INDUSTRY

Sponsor Role: collaborator

Daniel Hanley

OTHER

Sponsor Role: lead

Responsible Party

Daniel Hanley

MD

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Daniel F. Hanley, MD

Role: STUDY_CHAIR

Johns Hopkins University

Mario Zuccarello, MD

Role: PRINCIPAL_INVESTIGATOR

University of Cincinnati

Paul Vespa, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, Los Angeles

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Barrow Neurosurgical Associates

Phoenix, Arizona, United States

University of California Los Angeles

Los Angeles, California, United States

Stanford University

Palo Alto, California, United States

University of California, San Diego

San Diego, California, United States

Hartford Hospital

Hartford, Connecticut, United States

Georgetown University

Washington D.C., District of Columbia, United States

Mayo Clinic

Jacksonville, Florida, United States

Rush University

Chicago, Illinois, United States

University of Chicago

Chicago, Illinois, United States

NorthShore University Health System

Evanston, Illinois, United States

University of Maryland Medical Systems

Baltimore, Maryland, United States

Johns Hopkins University/Bayview Medical Center

Baltimore, Maryland, United States

Henry Ford Health System

Detroit, Michigan, United States

JFK Medical Center New Jersey

Edison, New Jersey, United States

Mt. Sinai Medical Center

New York, New York, United States

University of Cincinnati

Cincinnati, Ohio, United States

Case Western University

Cleveland, Ohio, United States

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Temple University

Philadelphia, Pennsylvania, United States

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

University of Texas, Houston

Houston, Texas, United States

University of Texas HSC, San Antonio

San Antonio, Texas, United States

Virginia Commonwealth University

Richmond, Virginia, United States

Montreal Neurological Institute at McGill University

Montreal, Quebec, Canada

University of Heidelberg

Heidelberg, , Germany

Newcastle General Hospital

Newcastle, , United Kingdom

Countries

United States; Canada; Germany; United Kingdom

References

Hansen BM, Ullman N, Muschelli J, Norrving B, Dlugash R, Avadhani R, Awad I, Zuccarello M, Ziai WC, Hanley DF, Thompson RE, Lindgren A; MISTIE and CLEAR Investigators. Relationship of White Matter Lesions with Intracerebral Hemorrhage Expansion and Functional Outcome: MISTIE II and CLEAR III. Neurocrit Care. 2020 Oct;33(2):516-524. doi: 10.1007/s12028-020-00916-4.

Reference Type: DERIVED

PMID: 32026447 (View on PubMed)

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. doi: 10.1161/STROKEAHA.116.013837. Epub 2016 Oct 6.

Reference Type: DERIVED

PMID: 27758940 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27751554 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26451031 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26243227 (View on PubMed)

Other Identifiers

R01NS046309

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ICH01

Identifier Type: -

Identifier Source: org_study_id