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MISTIE III Trial

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Description

MISTIE III, an international phase 3 clinical trial, was part of a long-term, ongoing effort to define successful treatment for ICH, and was recently presented as a late-breaking session at the 2019 ISC in Honolulu in February and published in The Lancet.

Description

  • The MISTIE III intervention seeks to remove blood from the brain through minimally invasive surgery and intermittent dosing of alteplase. The study premise is that by removing the blood clot faster than natural removal, injury to the brain will be reduced and the patient’s long-term prognosis will improve.
  • The MISTIE III trial is the culmination of the thrombolysis program spanning over 20 years of work by the trial Principal Investigators (PIs).
Learning Objectives
  • Interpret the results from the MISTIE III trial
  • Construct a rational approach to the patient with an ICH
  • Evaluate the comparative effectiveness of minimally invasive ICH therapies
  • Recommend future steps in the study and surgical treatment of ICH

Contributors

  • Daniel Hanley, MD

    Since 1996, Dr. Hanley has been a Professor of Neurology, Neurosurgery and Anesthesia/Critical Medicine at Johns Hopkins Medical Institutions. Since 1999, Dr. Hanley has also been Professor, School of Nursing, the Jeffrey and Harriett Legum Professor of Acute Care Neurology and Director of Brain Injury Outcomes Program at Johns Hopkins Medical Institutions. Dr. Hanley is a graduate of Williams College and Cornell University Medical College and has board certification in internal medicine, neurology and psychiatry. Dr. Hanley is a leading expert on multiple types of brain injury and has received more than 40 clinical and basic research grants, predominately from the National Institute of Health and the FDA Orphan drugs program. He has published more than 190 articles in peer-reviewed journals, has received the Alexander Humboldt Research Prize for his accomplishments in brain injury research and has extensive clinical trials experience in that field. His trainees are directors of over 20 brain intensive care units across the United States. Dr. Hanley is on the board of directors of the National Stroke Association and has developed nationally recognized education and training programs for that organization. He has significant experience in the areas of clinical trials design, organization and interpretation: drug development: device development and regulatory compliance. He is the principle investigator for the NIH sponsored MISTIE and CLEAR trials investigating minimally invasive neurosurgical techniques to treat hemorrhagic stroke.

  • Issam Awad, MSc, MD

    Dr. Awad is widely recognized for career long contributions and special skills in Neurovascular Surgery. He has made numerous scientific discoveries including the characterization of subcortical ischemic lesions in the aged, advances in the understanding of the natural history and biologic behavior of vascular malformations of the brain, and technical developments in neurovascular and epilepsy surgery. His research has been funded by the National Institutes of Health since 1998, focusing currently on molecular mechanisms of cerebral vascular malformations and their biomarkers, and minimally invasive techniques for treating hemorrhagic stroke. Awad’s innovations are changing neurosurgical practice throughout the world, and he has trained scores of neurosurgeons, some of whom are leaders of neurosurgical departments in a number of countries. His scholarly work has been cited more than 35,000 times (H Index 84). Dr. Awad has served in leadership roles at several national professional societies, he has been inducted in the Association of American Physicians, and he currently serves on the U.S. National Advisory Council for Neurological Disorders and Stroke.

  • Wendy Ziai, MD, MPH, FAHA

    Dr. Ziai is Associate Professor of Neurology, Neurosurgery and Anesthesia/Critical Medicine at Johns Hopkins Medical Institutions. Dr. Ziai is a graduate of Carleton University and Queen’s University in Canada, and the Johns Hopkins Bloomberg School of Public Health, and has board certification in Neurology and Neurocritical Care. Dr. Ziai is an expert on multiple types of brain injury and has published over 50 articles in peer-reviewed journals. She received the American Academy of Neurology Foundation Clinical Research Training Fellowship Award and has pursued research in mechanisms of injury and recovery in intracerebral hemorrhage with a specific interest in the acute management of intraventricular hemorrhage. She has significant theoretical and practical knowledge in clinical trials methodology and has been closely involved in managing aspects of the NIH sponsored MISTIE and CLEAR trials investigating minimally invasive neurosurgical techniques to treat hemorrhagic stroke. She has unique experience in the safety management of high acuity brain injured patients. A related focus of Dr. Ziai’s research pertains to the role of the inflammatory response in intracerebral and intraventricular hemorrhage. She leads a multicenter substudy investigating the temporal profile of central nervous system and peripheral inflammatory markers in patients treated with minimally invasive surgery in the MISTIE III trial and the impact of clot reduction. This study is currently supported by the NIH funded MISTIE trial for which Johns Hopkins is the coordinating center. Dr. Ziai is Fellowship program Director for the Johns Hopkins University Neurocritical Care Fellowship program and Co-Director of the Bayview Medical Center Neurocritical Care Unit. She also directs the Neurovascular Laboratory at the Johns Hopkins Hospital, and has been on the Board of directors of the Neurocritical Care Society (NCS). She is on the research committee of the NCS and has mentored numerous Neurocritical Care fellows.

  • George Lopez, MD, PhD

    George Lopez is a Neurointensivist, with specialty training in cerebrovascular diseases, and is currently an Associate Professor in Neurology. He is board certified in Neurology, Neurocritical Care, and Vascular Neurology. His clinical and research interests are centered on acute brain injuries including intracranial hemorrhage, subarachnoid hemorrhage, acute ischemic stroke, coma and cerebral resuscitation after cardiac arrest. As a clinical and translational research trialist, he has served as the site Principal Investigator for both the CLEAR-III and MISTIE-III trials. He regularly presents lectures at national and international meetings on advances in neurocritical care, minimizing secondary brain injury, and new stroke treatments, with an emphasis on practical clinical implementation.