A randomized 500-subject open-label phase 3 clinical trial of minimally invasive surgery plus alteplase in intracerebral hemorrhage evacuation (MISTIE III)

On Behalf of the MISTIE III Investigators

Research output: Contribution to journalArticle

Abstract

Rationale and hypothesis: Surgical removal of spontaneous intracerebral hemorrhage may reduce secondary destruction of brain tissue. However, large surgical trials of craniotomy have not demonstrated definitive improvement in clinical outcomes. Minimally invasive surgery may limit surgical tissue injury, and recent evidence supports testing these approaches in large clinical trials. Methods and design: MISTIE III is an investigator-initiated multicenter, randomized, open-label phase 3 study investigating whether minimally invasive clot evacuation with thrombolysis improves functional outcomes at 365 days compared to conservative management. Patients with supratentorial intracerebral hemorrhage clot volume ≥ 30 mL, confirmed by imaging within 24 h ofknown symptom onset,and intact brainstem reflexes were screened with a stability computed tomography scan at least 6 h after diagnostic scan. Patients who met clinical and imaging criteria (no ongoing coagulopathy; no suspicion of aneurysm, arteriovenous malformation, or any other vascular anomaly; and stable hematoma size on consecutive scans) were randomized to either minimally invasive surgery plus thrombolysis or medical therapy. The sample size of 500 was based on findings of a phase 2 study. Study outcomes: The primary outcome measure is dichotomized modified Rankin Scale 0–3 vs. 4–6 at 365 days adjusting for severity variables. Clinical secondary outcomes include dichotomized extended Glasgow Outcome Scale and all-cause mortality at 365 days; rate and extent of parenchymal blood clot removal; patient disposition at 365 days; efficacy at 180 days; type and intensity of ICU management; and quality of life measures. Safety was assessed at 30 days and throughout the study.

Original languageEnglish (US)
JournalInternational Journal of Stroke
DOIs
StatePublished - Jan 1 2019

Fingerprint

Phase III Clinical Trials
Minimally Invasive Surgical Procedures
Cerebral Hemorrhage
Tissue Plasminogen Activator
Outcome Assessment (Health Care)
Glasgow Outcome Scale
Craniotomy
Arteriovenous Malformations
Intraoperative Complications
Hematoma
Sample Size
Brain Stem
Aneurysm
Blood Vessels
Reflex
Thrombosis
Tomography
Quality of Life
Research Personnel
Clinical Trials

Keywords

  • intracerebral hemorrhage
  • minimally invasive surgery
  • protocols
  • Randomized controlled trial
  • stroke
  • surgery
  • thrombolysis

ASJC Scopus subject areas

  • Neurology

Cite this

@article{301469cd58664e8fb4493b1042ee7913,
title = "A randomized 500-subject open-label phase 3 clinical trial of minimally invasive surgery plus alteplase in intracerebral hemorrhage evacuation (MISTIE III)",
abstract = "Rationale and hypothesis: Surgical removal of spontaneous intracerebral hemorrhage may reduce secondary destruction of brain tissue. However, large surgical trials of craniotomy have not demonstrated definitive improvement in clinical outcomes. Minimally invasive surgery may limit surgical tissue injury, and recent evidence supports testing these approaches in large clinical trials. Methods and design: MISTIE III is an investigator-initiated multicenter, randomized, open-label phase 3 study investigating whether minimally invasive clot evacuation with thrombolysis improves functional outcomes at 365 days compared to conservative management. Patients with supratentorial intracerebral hemorrhage clot volume ≥ 30 mL, confirmed by imaging within 24 h ofknown symptom onset,and intact brainstem reflexes were screened with a stability computed tomography scan at least 6 h after diagnostic scan. Patients who met clinical and imaging criteria (no ongoing coagulopathy; no suspicion of aneurysm, arteriovenous malformation, or any other vascular anomaly; and stable hematoma size on consecutive scans) were randomized to either minimally invasive surgery plus thrombolysis or medical therapy. The sample size of 500 was based on findings of a phase 2 study. Study outcomes: The primary outcome measure is dichotomized modified Rankin Scale 0–3 vs. 4–6 at 365 days adjusting for severity variables. Clinical secondary outcomes include dichotomized extended Glasgow Outcome Scale and all-cause mortality at 365 days; rate and extent of parenchymal blood clot removal; patient disposition at 365 days; efficacy at 180 days; type and intensity of ICU management; and quality of life measures. Safety was assessed at 30 days and throughout the study.",
keywords = "intracerebral hemorrhage, minimally invasive surgery, protocols, Randomized controlled trial, stroke, surgery, thrombolysis",
author = "{On Behalf of the MISTIE III Investigators} and Ziai, {Wendy C} and Nichol McBee and Karen Lane and Lees, {Kennedy R.} and Jesse Dawson and Paul Vespa and Richard Thompson and Mendelow, {A. David} and Kase, {Carlos S.} and Juan Carhuapoma and Carol Thompson and Steven Mayo and Pat Reilly and Scott Janis and Anderson, {Craig S.} and Harrigan, {Mark R.} and Camarata, {Paul J.} and Caron, {Jean Louis} and Mario Zuccarello and Awad, {Issam A.} and Hanley, {Daniel F}",
year = "2019",
month = "1",
day = "1",
doi = "10.1177/1747493019839280",
language = "English (US)",
journal = "International Journal of Stroke",
issn = "1747-4930",
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T1 - A randomized 500-subject open-label phase 3 clinical trial of minimally invasive surgery plus alteplase in intracerebral hemorrhage evacuation (MISTIE III)

AU - On Behalf of the MISTIE III Investigators

AU - Ziai, Wendy C

AU - McBee, Nichol

AU - Lane, Karen

AU - Lees, Kennedy R.

AU - Dawson, Jesse

AU - Vespa, Paul

AU - Thompson, Richard

AU - Mendelow, A. David

AU - Kase, Carlos S.

AU - Carhuapoma, Juan

AU - Thompson, Carol

AU - Mayo, Steven

AU - Reilly, Pat

AU - Janis, Scott

AU - Anderson, Craig S.

AU - Harrigan, Mark R.

AU - Camarata, Paul J.

AU - Caron, Jean Louis

AU - Zuccarello, Mario

AU - Awad, Issam A.

AU - Hanley, Daniel F

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Rationale and hypothesis: Surgical removal of spontaneous intracerebral hemorrhage may reduce secondary destruction of brain tissue. However, large surgical trials of craniotomy have not demonstrated definitive improvement in clinical outcomes. Minimally invasive surgery may limit surgical tissue injury, and recent evidence supports testing these approaches in large clinical trials. Methods and design: MISTIE III is an investigator-initiated multicenter, randomized, open-label phase 3 study investigating whether minimally invasive clot evacuation with thrombolysis improves functional outcomes at 365 days compared to conservative management. Patients with supratentorial intracerebral hemorrhage clot volume ≥ 30 mL, confirmed by imaging within 24 h ofknown symptom onset,and intact brainstem reflexes were screened with a stability computed tomography scan at least 6 h after diagnostic scan. Patients who met clinical and imaging criteria (no ongoing coagulopathy; no suspicion of aneurysm, arteriovenous malformation, or any other vascular anomaly; and stable hematoma size on consecutive scans) were randomized to either minimally invasive surgery plus thrombolysis or medical therapy. The sample size of 500 was based on findings of a phase 2 study. Study outcomes: The primary outcome measure is dichotomized modified Rankin Scale 0–3 vs. 4–6 at 365 days adjusting for severity variables. Clinical secondary outcomes include dichotomized extended Glasgow Outcome Scale and all-cause mortality at 365 days; rate and extent of parenchymal blood clot removal; patient disposition at 365 days; efficacy at 180 days; type and intensity of ICU management; and quality of life measures. Safety was assessed at 30 days and throughout the study.

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KW - intracerebral hemorrhage

KW - minimally invasive surgery

KW - protocols

KW - Randomized controlled trial

KW - stroke

KW - surgery

KW - thrombolysis

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