Earlier this month, on April 3, PI: Alan Hoffer and Coordinator: Val Cwiklinski at Case Western Reserve University Hospital enrolled the last MISTIE-ICES subject, therefore closing the trial to enrollments!  The MISTIE-ICES Trial opened in mid-2008 and has since enrolled 20 subjects across five centers: Barrow Neurological Institute, Case Western Reserve University Hospital, University of California, Los Angeles, University of California, San Diego and the University of Pittsburgh Medical Center.

The MISTIE-ICES Trial is the 3^rd tier in Stage I of the MISTIE Trial.  The purpose of the MISTIE-ICES Trial is to determine the safety of using either endoscopic surgery (ICES) or a combination of minimally invasive surgery and clot lysis with rt-PA (MISTIE) to remove intracerebral hemorrhage.  The ICES arm is led by Drs. Paul Vespa and Neil Martin at the University of California, Los Angeles and Dr. Dan Hanley at Johns Hopkins University.

To all CLEAR III and MISTIE-ICES collaborators and guests,

You are invited to attend an open house for the CLEAR III and MISTIE‐ICES clinical trials to be held during the American Association of Neurological Surgeons (AANS) Meeting 2012 in Miami, Florida, USA. 

It is on Monday, April 16, 2012 beginning at 5:30pm

Surfcomber Hotel – Miami South Beach (1/2 mile walk from the Convention Center)

1717 Collins Avenue

Miami Beach, Florida 33139

(LongBoard Room)

Refreshments will be served.

Please note: we cannot support any travel needs

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.

After a tremendous effort over several months by all of the staff at the Johns Hopkins BIOS (Brain Injury Outcomes) coordinating center as well as the coordinators and investigators at over 35 investigational sites, we are happy to announce that a grant application has been submitted to the National Institute of Neurological Disorders and Stroke (NINDS, part of the National Institute of Health or NIH) requesting funding for the next phase in the MISTIE clinical development program.

If approved by NINDS, MISTIE III will be a phase III, 500-patient, multicenter, international clinical trial to assess the efficacy and safety of using minimally-invasive surgery (MIS, basically inserting a small catheter into the brain) and a thrombolytic drug (tissue plasminogen activator or tPA, administered via this catheter) to rapidly reduce the size of an intracerebral hematoma (ICH, a blood clot in the brain). The goal will be to determine with statistical power if this rapid reduction of the ICH using the MIS+tPA approach definitively leads to reduced mortality/morbidity and improved functional outcomes (better quality of life, better physical and mental function) compared to standard medical care alone. Preliminary data from the MISTIE phase II trial which recently completed enrollment has given a strong signal that the MISTIE treatment, by shortening the duration of physical and biochemical injury to the brain caused by the hematoma, is beneficial to the patient. In statistical terms, MISTIE II has shown that, when surgeons reduce the clot to under 15cc over a 1-3 day period using this approach, the odds for benefit, as measured by dichotomized Modified Rankin Scale (0-3), are 3.6 times better (p=0.053).

If this clinical improvement can be validated in this MISTIE III trial, it will undoubtedly lead to a major change in the way ICH is treated throughout the world. Currently, there is no proven alternative treatment for ICH (other than just intensive ICU care) and an unacceptably high percentage of ICH patients die or end up with major mental and physical handicap. For medical researchers like us, this is the kind of effort that you want to tell your grandchildren that you were part of, a chance to possibly change the way medicine is practiced around the world and potentially improve the hundreds of thousands of thousands of people who suffer after a hemorrhagic stroke.

Hopefully, NINDS will approve the funding in December 2012 and the trial will begin shortly thereafter. As we gear-up for this trial, we will post further details here on this website. Meanwhile, the anxious waiting begins.