Hemicraniectomy in Older Patients with Extensive Middle-Cerebral-Artery Stroke DESTINY II TRIAL Katherine Steele 7 April 2014

Why choose this trial? DECIMAL, DESTINY and HAMLET trials Improved morbidity and mortality in younger patient groups: Increased 1 year survival from 29% to 78% Increased rate of mild-mod disability 43% vs. 21% conservative management Rate of survival with severe disability low in both groups

DESTINY II TRIAL Prospective, randomised controlled multi center trial - 13 sites throughout Germany: August 2009 - May 2013 112 patients > 61 years (61-82 with median 70 years) Comparison of outcomes of malignant MCA ischaemic stroke: Control group - conservative management Treatment group - early hemicraniectomy Limited to patients admitted to the ICU Primary endpoint: Modified Rankin score at 6 months Secondary endpoints: 12 months survival, disability, depression and satisfaction

Inclusion Criteria 61 years of age or older Acute unilateral MCA stroke symptoms Onset of symptoms <48hrs before treatment initiation National Institutes of Health Stroke Scale (NIHSS) scores: >14 (non-dominant hemisphere) with reduced level of consciousness >19 (dominant hemisphere) with reduced level of consciousness Ischaemic infarction of at least 2/3 of the MCA territory, including basal ganglia, on imaging

Exclusion Criteria Pre-existing score of >1 on the modified Rankin scale OR Pre-existing score of <95 on the Barthel Index Absence of pupillary reflexes GCS < 6 Haemorrhages or other associated brain lesions Contraindications to surgery Estimated life expectancy of < 3 years

Treatments Initiated within 48 hours of onset of symptoms, no later than 6 hours after randomisation Therapies for the control group included the following: Basic therapy in the ICU for stroke Osmotherapy - mannitol, glycerol or hypertonic hydroxyethyl starch Sedation, intubation and mechanical ventilation Hyperventilation Buffer solutions Surgical treatment: large hemicraniectomy (diameter at least 12cm) and duroplasty

Results - primary endpoint at 6 months Patient recruitment was stopped after 82 patients assessed for the primary endpoint (6 months) Hemicraniectomy group - 40 patients (9 additional) Control group - 42 patients (21 additional) Modified Rankin score of 4 or less: Hemicraniectomy group: 20 out of 49 patients Control group: 10 out of 63 patients Mortality at 6 months: 33% surgery vs. 70% control

Results - primary endpoint at 6 months

Secondary Endpoint: 12 months

Secondary Endpoint: 12 months

Secondary Endpoint: 12 months

Secondary Endpoint: 12 months

Secondary Endpoint: 12 months

Points for Discussion Trial design - initial design: sample size determined for 90% power Sample size Heterogeneity of groups Statistical significance of endpoints Morbidity after intervention - is intervention worth it?