WP03 - Clinical trial

This WP will comprise the conduction of the clinical trial of WAKE-UP.

The trial will be an investigator initiated European multicentre interventional, treatment, randomised, double-blind, placebo-controlled, parallel assignment, efficacy and safety study. The objective will be to assess efficacy and safety of MRI-based thrombolysis with intravenous Alteplase in patients with ischemic stroke waking up with stroke symptoms or with unknown symptom onset.

Clinical inclusion criteria will follow approval criteria for intravenous thrombolysis except for the inclusion of patients with unknown symptom onset. Inclusion of patients will be based on acute stroke MRI findings indicative of ischemic lesions ≤4.5 hours old: acute ischemic lesion visible on DWI but no marked parenchymal hyperintensity visible on FLAIR (DWI-FLAIR-mismatch). Patients will be randomised to treatment with either intravenous Tissue Plasminogen Activator (Alteplase) or placebo. Primary outcome will be “favourable outcome” defined by a score of 0-1 on the modified Rankin Scale (MRS) 90 days after stroke as in previous stroke thrombolysis trials. Secondary endpoints will comprise a global outcome score, categorical shift in MRS, responder analysis. Primary safety endpoints will be mortality at 90 days, death or dependency at 90 days, and symptomatic intracerebral haemorrhage (SICH). It is planned to enrol 800 patients (400 patients per group).

The clinical trial will be organised by a central coordinating centre (UKE) and six national coordinating centres represented by the clinical project partners (AUH, Charité, IDIBGi, KUL, HCL, UG). Patients will be enrolled in approximately 40 recruiting centres in six European countries. Study medication will be provided by participant 11 (ZytoService). Trial monitoring will be performed by partner 13 (ORION). Statistical analysis will be performed in WP06. DSMB and EAB will be constituted in WP04. CIRB will be constituted in WP05.

This WP will be led by participant 01 (C. Gerloff, UKE). The WP will be active during Month 01-60.

Participants involved in WP03: