Dr. Daniel F. Hanley presented the results of the MISTIE Phase II trial today at the International Stroke Conference (ISC) in New Orleans. A copy of the abstract, presentation slides and the video are available in this article (click CONTINUE READING for the full article). Also, be sure to see Gayane Yenokyan's recent presentation to the CLEAR III investigators and coordinators on the preliminary outcomes data.
MISTIE Phase II Results: Safety, Efficacy and Surgical Performance
Background: We report the primary clinical outcome results (180 day mRS) for the “Minimally Invasive Surgery plus t-PA for Intracerebral Hemorrhage Evacuation” (MISTIE) trial, a NINDS-funded, two-stage, study of safety, efficacy, and surgical performance that continued to completion after a planned interim analysis showed a strong indication of safety, and efficacy.
Results: 93 subjects were randomized to minimally invasive surgery (MIS) plus t-PA (n=54) or medical therapy (n=39). This population was 66% male, average age 61 ± 12 yrs., with 65% basal ganglia/35% lobar locations. At presentation, the clot size was: ICH, 40mL ± 21; IVH, 3mL ± 7; with functional levels of Glasgow Coma Scale 10 ± 3 and NIH Stoke Scale 22 ± 9. As of October 31, 2011, follow up is 93% complete and demonstrates: the safety profile for the surgical group was within specified thresholds; mortality levels at 7, 30 & 180 days were 1.0%, 11.8% and 23.7% respectively; rebleeding was observed in 5.4% of subjects; and there was one instance of brain infection. Clot removal rates were 19%/day for subjects receiving 0.3 mg, and 21%/day for 1.0 mg. Removal rates for the treatment groups were significantly higher than in medical subjects (5%/ day). A strong correlation between accuracy of catheter placement and resulting residual clot volume at the end-of-treatment was demonstrated (Spearman rho= -0.651). Subject demographics, clot location, and duration of treatment do not appear to affect this relationship.
Logistic regression revealed baseline factors (GCS and NIHSS) and ICH/IVH clot volumes at presentation and end of treatment were predictors of good functional outcome (modified Rankin 0-3) at 180 days. Surgical extraction of clot was associated with increased likelihood of mRS 0-3 (odds ratio 1.8 / 10 cc remaining; p=0.005). When surgeons produced end-of-treatment clot volumes of < 15cc, the odds for benefit using dichotomized mRS was 3.6 (p=0.053).
Conclusions: MIS appears safe compared to medical therapy and produces surgically significant removal of clot without craniotomy. Treatment via MISTIE may benefit ICH patients because effective removal occurs and there appears to be limited tissue injury. Confirmation of these clinically significant benefits in a Phase III trial would lead to a major change in practice, as currently the majority of ICH patients do not undergo surgical treatment.
Authors: Daniel F Hanley, Karen Lane, John Hopkins Univ, Baltimore, MD; William C Broaddus, Virginia Commonwealth Univ, Richmond, VA; Issam Awad, Univ of Chicago, Chicago, IL; E Francois Aldrich, Univ of Maryland, Baltimore, MD; Christine Wijman, Stanford Univ Sch of Med, Palo Alto, CA; Paul Vespa, Univ of California, Los Angeles, CA; Jean-Louis Caron, Univ of Texas, San Antonio, San Antonio, TX; Judy Huang, John Hopkins Medical Inst, Baltimore, MD; Byron Bailey, Charleston Neurosurgical Associates, Roper St Francis Physicians, Charleston, NC; Marc LaPointe, Medical Univ of South Carolina, Charleston, NC; Joshua B Bederson, Mount Sinai Medical Ctr, New York, NY; Martin Gizzi, New Jersey Neuroscience Inst at JFK Medical Ctr, Edison, NJ; A David Mendelow, Newcastle Univ, Newcastle upon Tyne, United Kingdom; Richard E Temes, Rush Univ, Chicago, IL; Khaled Aziz, Allegheny General Hosp, Pittsburgh, PA; Jeffrey J Fletcher, Univ of Michigan Health System, Ann Arbor, MI; George Lopez, Univ of Texas, Houston, TX; J Ivan Lopez, Univ of Alabama at Birmingham, Birmingham, AL; Fernando Goldenberg, Univ of Chicago, Chicago, IL; Inam Kureshi, Hartford Hosp, Hartford, CT; Sven Poli, Thorsten Steiner, UnivsKlinikum Heidelberg, Heidelberg, Germany; John Muschelli, John Hopkins Bloomberg Sch of Public Health, Baltimore, MD; Mario Zuccarello, Univ of Cincinnati, Cincinnati, O
|Phase II results slides from ISC 2012 - PDF||1 MB|