Minimally Invasive Surgery and rtPA for Intracerebral Hemorrhage Evacuation "MISTIE"

Completed

Phase 2 Results

Trial 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 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

Interventions

  • Alteplase Drug
    Intervention Desc: IV
  • Cathflo Activase (drug) Drug
    Other Names: rtPA
    Intervention Desc: 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, 1.0, or 3.0 mg of recombinant tissue plasminogen activator, rt-PA, CathFlo®) through the catheter once every eight hours for up to 72 hours with best medical care.
    ARM 1: Kind: Experimental
    Label: Medical Managment
    ARM 2: Kind: Experimental
    Label: Surgical Management
  • MIS+Cathflo Activase (drug) Drug
    Other Names: rtPA
    Intervention Desc: 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.
    ARM 1: Kind: Experimental
    Label: MISTIE Surgical Management
    Description: Minimally invasive surgery with clot lysis with rt-PA.
  • Intraoperative stereotactic CT-Guided Endoscopic Surgery Procedure
    Intervention Desc: 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.
    ARM 1: Kind: Experimental
    Label: ICES Surgical Management
    Description: Endoscopic removal of ICH

Trial Design

  • Allocation: Randomized
  • Masking: Open Label
  • Purpose: Treatment
  • Endpoint: Safety/Efficacy Study
  • Intervention: Parallel Assignment

Patient Involvement

Dose Finding (successive dose tiers, n=60), followed by a Safety Study (randomized, controlled trial, n=50).

Outcomes

Type Measure Time Frame Safety Issue
Primary 30-day mortality; procedure related mortality; incidence of cerebritis, meningitis; rate of rebleeding.
Secondary Rate of clot size reduction at Days 4-5 determined by CT scans; 90 & 180 day GOS, Rankin, Stroke Impact Scale.
Primary Mortality 30 days Yes
Primary Procedure related mortality 30 days Yes
Primary Incidence of cerebritis, meningitis 30 days Yes
Primary Rate of rebleeding 30 days Yes
Secondary Rate of clot size reduction at Days 4-5 determined by CT scans 180 days Yes
Secondary 90- & 180-day GOS, eGOS, Rankin, Stroke Impact Scale 180 days Yes
Secondary Post-operative size reduction 180-days Yes
Secondary 90-, 180-, & 365-day GOS, eGOS, Rankin, Stroke Impact Scale 365 days No
Primary Safety Outcome Number 1: Rate of Mortality 30 days from randomization Yes
Primary Safety Outcome Number 2: Rate of Procedure-related Mortality 7 days from randomization Yes
Primary Safety Outcome Number 3: Rate of Cerebritis, Meningitis, Bacterial Ventriculitis 30 days from randomization Yes
Primary Safety Outcome Number 4: Rate of Symptomatic Rebleeding 72 hours post last dose Yes
Primary Efficacy Outcome Number 1: Dichotomized Modified Rankin Scale (mRS) at Day 180 180 days from randomization No
Secondary Ordinal Modified Rankin Scale (mRS) at Day 180 180 days from randomization No
Secondary Ordinal Modified Rankin Scale (mRS) at Day 365 365 days from randomization No
Secondary Clot Size Reduction by End of Treatment Time from randomization until end of treatment, up to 10 days No
Secondary Post-operative Clot Size Reduction Time from post-operation until end of treatment, up to 10 days No

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