Enlighten-Research publications by members of the University of Glasgow http://eprints.gla.ac.uk Minimally invasive surgery with thrombolysis in intracerebral haemorrhage evacuation (MISTIE III): a randomised, controlled, open-label phase 3 trial with blinded endpoint

BACKGROUND:Minimally invasive surgery procedures, including stereotactic catheter aspiration and clearance of intracerebral hemorrhage (ICH) with recombinant tissue plasminogen activator hold a promise to improve outcome of supratentorial brain hemorrhage, a morbid and disabling type of stroke. A recently completed Phase III randomized trial showed improved mortality but was neutral on the primary outcome (modified Rankin scale score 0 to 3 at 1 yr). OBJECTIVE: To assess surgical performance and its impact on the extent of ICH evacuation and functional outcomes. METHODS: Univariate and multivariate models were used to assess the extent of hematoma evacuation efficacy in relation to mRS 0 to 3 outcome and postulated factors related to patient, disease, and protocol adherence in the surgical arm (n = 242) of the MISTIE trial. RESULTS: Greater ICH reduction has a higher likelihood of achieving mRS of 0 to 3 with a minimum evacuation threshold of ≤15 mL end of treatment ICH volume or ≥70% volume reduction when controlling for disease severity factors. Mortality benefit was achieved at ≤30 mL end of treatment ICH volume, or >53% volume reduction. Initial hematoma volume, history of hypertension, irregular-shaped hematoma, number of alteplase doses given, surgical protocol deviations, and catheter manipulation problems were significant factors in failing to achieve ≤15 mL goal evacuation. Greater surgeon/site experiences were associated with avoiding poor hematoma evacuation. CONCLUSION: This is the first surgical trial reporting thresholds for reduction of ICH volume correlating with improved mortality and functional outcomes. To realize the benefit of surgery, protocol objectives, surgeon education, technical enhancements, and case selection should be focused on this goal.

Background Intraventricular hemorrhage is a significant cause of mortality and morbidity worldwide. Treating intraventricular hemorrhage with intraventricular fibrinolytic therapy via a catheter is becoming an increasingly utilized intervention. Aims This meta-analysis aimed to investigate the role of intraventricular fibrinolytic treatment in hypertensive intraventricular hemorrhage patients and evaluate the effect sizes for survival as well as level of function at differing time points. Summary of review PubMed, CNKI, VIP, and Wanfang were searched using the terms "IVH" and "IVH and ICH" for human studies with adult patients published between January 1950 and July 2016. Seventeen publications were selected. Data analysis showed lower rates of mortality in the treatment group at 30 days ( P < 0.001), 180 days ( P = 0.001), 365 days ( P = 0.40), and overall ( P < 0.001). Pooling modified Rankin Scale and Glasgow outcome scale data, the treatment group had more good functional outcomes at 30 days ( P = 0.38), 90 days ( P = 0.04), 180 days ( P = 0.31), 365 days ( P = 0.76), and overall ( P = 0.02). Good functional outcome was defined as modified Rankin Scale score of 0 to 3 or a Glasgow outcome scale score of 3 to 5. Conclusions Intraventricular fibrinolytic for treatment of hypertensive intraventricular hemorrhage reduces mortality and potentially leads to an increased number of good functional outcomes. Different functional outcome scales (modified Rankin Scale or Glasgow outcome scale) produce different effect sizes. Intraventricular fibrinolytic treatment may offer intraventricular hemorrhage patients a targeted therapy that produces meaningful mortality benefit and possible functional outcome benefits.

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