Timeisbrain

Intracerebral hemorrhage (ICH) accounts for 10-15% of all strokes and is associated with a high early mortality and poor long term functional outcomes. It is the only subtype of stroke which still does not have a proven and effective treatment available. Clinical trials investigating craniotomy and surgical evacuation of the hematoma have not shown improvement in outcomes^1,2. Current in-hospital treatment of ICH has mainly involved medical stabilization and management of complications. More recently, there has been an increased interest in minimally invasive surgical methods for hematoma removal as a treatment strategy for intracerebral hemorrhage³.

Results of the recently concluded MISTIE III trial were presented at the International Stroke Conference in Honolulu earlier this week. This was an open label phase 3 trial which evaluated if minimally invasive catheter evacuation followed by thrombolysis can improve functional outcomes in ICH. The trial enrolled 499 adult patients with spontaneous/non traumatic supratentorial intracerebral hemorrhage measuring at least 30 ml. The patients were randomized 1:1 into the MISTIE and standard medical care groups.  Patients with a vascular etiology, such as an AVM or with an infratentorial hemorrhage were excluded from the study. The MISTIE treatment involved image guided catheter evacuation of the hemorrhage utilizing local thrombolysis with 1 mg alteplase doses given every 8 hours, up to a total of 9 doses.

Primary outcome was defined as a good functional outcome measured by modified Rankin Scale score of 0-3 at 1 year. 45% patients in the MISTIE group achieved the target primary outcome as compared to 41% in the medical care group. The 30 day mortality rates were 9% in the MISTIE group and 15% in the standard medical group. These results were not statistically significant to indicate a benefit of the minimally invasive surgical treatment. There was no significant difference in the rates of symptomatic bleeding and brain bacterial infections between the two treatment arms. Removal of the hematoma volume was associated with a significant increase in the probability of good outcomes. Patients who achieved final hematoma volume of less than 15 ml were more likely to have a good functional outcome in the MISTIE group:  53.4% vs. 41.9%, with p =0.03.

Even though the results were neutral without a signal towards overall benefit, this study does show that the minimally invasive surgery can be safely performed without an increase in the rates of death or other serious adverse outcomes. This is a promising result and should encourage further studies evaluating minimally invasive surgical treatments for ICH. Three ongoing trials are evaluating minimally invasive surgical treatments for ICH: ENRICH, INVEST and MIND (www.clinicaltrials.gov). With improved procedural protocols in the future, lowered hematoma volumes could be obtained more consistently, which would lead to better functional outcomes for this devastating neurological condition.

References:

1. Mendelow AD Gregson BA Fernandes HM et al.Early surgery versus initial conservative treatment in patients with spontaneous supratentorial intracerebral haematomas in the International Surgical Trial in Intracerebral Haemorrhage (STICH): a randomised trial. Lancet. 2005; 365: 387-397
2. Mendelow AD Gregson BA Rowan EN Murray GD Gholkar A Mitchell PM. Early surgery versus initial conservative treatment in patients with spontaneous supratentorial lobar intracerebral haematomas (STICH II): a randomised trial. Lancet. 2013; 382: 397-408
3. Hanley DF Lane K McBee N et al. Thrombolytic removal of intraventricular haemorrhage in treatment of severe stroke: results of the randomised, multicentre, multiregion, placebo-controlled CLEAR III trial. Lancet. 2017; 389: 603-611