The WAKE-UP project

WAKE-UP is a European multicentre investigator-initiated randomized placebo-controlled clinical trial of MRI based thrombolysis in acute stroke patients with unknown time of symptom onset, e.g. due to recognition of stroke symptoms on awakening.

Stroke is a devastating disease leading to death and disability in large numbers of patients with massive social and economic impact. Intravenous thrombolysis with Alteplase is available as effective and safe treatment of acute stroke within 4.5 hours of symptom onset. However, in about 20% of acute stroke patients time of symptom onset is unknown e.g. because symptoms are recognized when waking-up from sleep in the morning. This large group of patients is currently excluded from treatment with Alteplase only due to the missing information on the time of symptom onset. In preparatory work the WAKE-UP consortium has developed an innovative approach of using brain MRI as surrogate marker of stroke lesion age which may be used to identify stroke patients likely to benefit from thrombolysis.

The objective of WAKE-UP is to test efficacy and safety of MRI-based intravenous thrombolysis with Alteplase in patients waking up with stroke symptoms or patients with unknown symptom onset. By this, WAKE-UP aims at providing a new safe and effective treatment option for acute stroke patients waking up with stroke symptoms.

The project is centrally coordinated by the Universitätsklinikum Hamburg-Eppendorf (Prof. Christian Gerloff; deputy coordinator: Dr. Götz Thomalla).

NEWS

Experience the new page on our website where the WAKE-UP national coordinators tell what they think about our trial!!!

Patient enrollment (30.06.2016)

As of June 30, 1.120 patients were enrolled in WAKE-UP with 407 patients randomized and 713 screen failures.

WAKE-UP Patient enrollment June 2016

The third year of the trial (30.09.2015)

On September 22, 2015 the WAKE-UP trial has been active for three years. By the end of the third year of the trial, 58 sites were active, and 851 patients have been enrolled of whom 312 have been randomised. During the third year of the trial the safety interim analysis was performed after 200 patients have completed the trial and reached the outcome evaluation after 80-100 days. On evaluation of these data the data and safety monitoring board (DSMB) was satisfied with general study conduct and concluded that there was no safety issue of concern. The DSMB has encouraged investigators to continue with enrolment into the WAKE-UP trial.

WAKE-UP Report has been accepted by the EC

The 3rd Periodic Report about the progress in WAKE-UP has just been accepted by the European Commission. Click here to read the publishable summary of the 3rd period.

First WAKE-UP & THAWS Meeting in Tokyo on April 30, 2015

We thank our friends from Japan for the outstanding hospitality and wish them great success with the THAWS trial. Pooled analyses will be very valuable. We had great scientific discussions! Read more about the THAWS trial in their protocol paper.

First WAKE-UP & THAWS Meeting in Tokyo on April 30, 2015
First WAKE-UP & THAWS Meeting in Tokyo on April 30, 2015

The second year of the trial (30.09.2014)

On September 22, 2014 the WAKE-UP trial has been active for two years. By the end of the second year of the trial, 48 sites were active, and 467 patients have been enrolled of whom 186 have been randomised. During the second year of the trial the first planned safety interim analysis was performed after 100 patients have completed the trial and reached the outcome evaluation after 80-100 days. On evaluation of these data the data and safety monitoring board (DSMB) was satisfied with general study conduct and concluded that there was no safety issue of concern. The DSMB has encouraged investigators to continue with enrolment into the WAKE-UP trial.

New paper in "Stroke" (20.02.2014)

Link

Japanese trial adapts WAKE-UP design (05.12.2013)

The Japanese THrombolysis with alteplase 0.6mg/kg body weight for Acute Wake-up and unclear-onset Stroke trial (THAWS) is planned following the WAKE-UP design except for the different dosage of alteplase which follows the licensing criteria in Japan. THAWS is an investigator initiated, multicenter, prospective, randomized, open label, blinded-endpoint assessment clinical trial. Patients with unclear-onset

time of stroke symptom beyond 4.5 h and within 12 h after symptom recognition will be evaluated with a multimodal MRI. Three hundred patients with a negative FLAIR pattern will be randomized 1:1 to either intravenous thrombolysis with alteplase of 0.6mg/kg body weight (n=150) or standard treatment (n=150). The principal investigator is Professor Kazunori Toyoda from the Department of Stroke and Cerebrovascular Diseases at the National Cerebral and Cardiovascular Center, Osaka. The THAWS investigators have asked the WAKE-UP consortium for cooperation, and the WAKE-UP Steering Committee has agreed on providing the training materials used for image training in WAKE-UP to the THAWS investigators. THAWS is planned to start enrolling in early 2014. The trial will help transfer the expected results of WAKE-UP to an Asian population.

First Annual Safety Report submitted (15.11.2013)

The first Annual Safety Report was submitted to all concerned Competent Authorities and Ethics Comittees. It covers the first year of the trial (September 23, 2012 – September 22, 2013). In summary no changes to the conduct of this study are warranted and the risk benefit assessment remains unchanged.

WAKE-UP DSMB meeting: no safety concerns (06.11.2013)

The WAKE-UP Data and Safety Monitoring Board (DSMB) met on November 6, 2013 and reviewed unblinded data of 129 screened patients of whom 61 had been randomised. The DSMB was satisfied with study conduct and concluded that there was no safety issues of concern. The DSMB encourages investigators to continue with enrolment to the Wake-Up trial.

The first year of the trial (30.09.2013)

On September 22, 2013 the WAKE-UP has been active for one year. The first site was initiated on 23 September 2012, and in the following months further sites were initiated in all participating six countries. By the end of the first year of the trial, 25 sites were active. The first patient was enrolled on October 12, 2012 at UKE, Hamburg, Germany. The first patient was randomized on November 26, 2012 at Aarhus, Denmark. By the end of the first year, 25 sites were active, and 129 have been enrolled of whom 61 have been randomised.