Lee Schwamm - US grants

The Access Core ofthe SPOTRIAS center at Partners will confinue to support the rapid administrafion of standard intravenous thrombolysis, the rapid evaluation and treatment of hemorrhagic stroke, as well as the execution of the four proposed research projects (two independent Partners projects and two collaborative projects with Columbia University) at the hwo Partners academic centers. The Access Core will also strive to increase its impact on stroke in the broader community by extending its acute stroke expertise within and across our extensive nehwork of Partners Healthcare System (PHS) and 26 TeleStroke-affiliated hospitals. This will help provide a platform from which to launch future SPOTRIAS network-wide stroke research. For the last two decades. Partners has enjoyed a rich clinical and research collaboration involving the Departments of Emergency Medicine, Radiology, Neurology, and Neurosurgery. The leadership of the Access Core reflects the integrated approach to acute stroke care across the system. The Access Core is co-directed by physicians from Neurology and Emergency Medicine who are institutional leaders in quality improvement, with addifional key leadership posifions held by active members of these departments at each site, all of whom care for acute stroke pafients in their clinical practice. In addifion, the two hospitals use the same acute stroke protocols, share the same acute stroke and NICU fellows and collaborate on the same acute stroke quality agenda. The Partners SPOTRIAS program is fully integrated into the daily activities of the clinical stroke care and stroke research activities at the two sites, and the Access Core is uniquely positioned to accomplish its goals because so many of the SPOTRIAS research faculties are also active members ofthe acute stroke clinical care delivery team. In pursuit of its aims, the Access Core will utilize the robust quality improvement infrastructure which Dr. Schwamm has developed across Partners for continued advancement of acute stroke care for patients within the broader context of a coordinated regional stroke network.

PROJECT SUMMARY (See instructions): Despite significant progress in stroke prevention and its acute treatment, stroke remains the third leading cause of death and a leading cause of adult morbidity worldwide. By defining stroke symptom onset in the most conservative manner, namely the time the patient was last seen well, many patients whose onset is unwitnessed are automatically ineligible for thrombolytic therapy even if their true time of onset would allow them to qualify. If a technique existed that could replace the human witness and testify that the stroke was in fact less than 3.5 hours duration, then these patients could be considered for alteplase treatment under current American Heart Association (AHA) guidelines, and be treated if eligible according to the inclusion and exclusion criteria. Many stroke patients are rapidly brought to the hospital within 3 hours of the time of symptom discovery, but FDA indications exclude them from consideration for intravenous alteplase if it has been greater than 3 hours since the time they were last known to be well. We propose to use advanced MR imaging as the witness to testify as to stroke duration in those patients who do not have a human witness in an open label Phase Ha safety study of thrombolysis in these patients. We have modeled the other eligibility criteria after the ECASS3 trial design and the current AHA guidelines in order to limit the variable of interest to the use of MR as the determinant of time of stroke onset. We will exclude patients from the study who arrive within 3 hours from last seen well since these patients are eligible for on-label treatment with thrombolysis. Because the study is open-label and investigators are unblinded, we will use the more conservative ECASS-2 definition of symptomatic ICH. This is defined as any hemorrhage with neurologic deterioration, as indicated by an NIHSS score that was higher by 4 points or more than the value at baseline or the lowest value in the first 7 days, or any hemorrhage leading to death, and does not require that the ICH be classified as causally linked to the neurologic deterioration. If our study is successful, we can potentially expand use of lyrics to a stroke patient population for whom little acute intervention is currently offered.

DESCRIPTION (provided by applicant): We propose to create the New England Regional Coordinating Center (NERCC), an integrated team of hospitals and EMS agencies in Boston and Western Massachusetts that will serve as a top-enrolling site and vibrant contributor to the NINDS Stroke Trials Network. Our group includes many of the major adult academic stroke centers in the Greater Boston area, and our 30 hospital New England TeleStroke referral network will extend our potential recruitment even further. All core hospitals have a proven track record of successful management and performance of clinical trials. In particular, all hospitals have an established research infrastructure that performs ongoing clinical research in stroke neurology with strong collaborations across disciplines. Principal investigator Lee H. Schwamm, MD, and Co-Investigators bring a complementary set of skills in managing successful translational clinical research programs, membership on Steering Committees, and positions of national leadership in their fields. Our team includes seasoned clinical investigators in vascular neurology, emergency medicine, neuroendovascular, neurosurgery, neurointensive care, neuroimaging, stroke rehabilitation, and preclinical basic and translational stroke investigation i both adults and children. Strengths of the NERCC team include 1) close personal and professional ties between multiple investigators; 2) large patient population from diverse hospital settings in a major metropolitan area; 3) talented teams of site investigators with track records o scientific achievement, innovation, and subject recruitment in multicenter trials; 4) robust existing NINDS-funded research and clinical trial management infrastructure; 5) existing clinical research programs, e.g., Neurology Clinical Research Institute, NIH Clinical and Translational Science Award programs at Boston University and across Harvard; Sites in the Specialized Programs of Translational Research in Acute Stroke (SPOTRIAS) and Neurology Emergency Treatment Trials and NeuroNEXT Clinical Coordinating Center. In addition, integration with Boston and Worcester prehospital services will be leveraged to support the goals of the NERCC. Overall, the NERCC Team has the resources, vision, and enthusiasm to develop new translational science and successfully execute the NINDS Stroke Trials Network Phase 1, 2 and 3 studies.