The WAKE-UP clinical trial

Can emergency treatment be extended to those waking up with a stroke?

About 20% of strokes occur during sleep. For patients waking up with stroke symptoms, the only approved treatment— the delivery of the blood clot busting drug tPA— is unavailable to them. Currently, tPA has only been proven effective when given to patients within 4.5 hours after the onset of stroke symptoms because there is concern about the risk of bleeding with treatment given later. If the start time of stroke is unknown, as it is in patients waking up with a stroke, the patients are not able to receive the drug.

WAKE-UP is a major clinical trial funded by the European Union to test the safety and effectiveness of tPA treatment in patients waking up with a stroke. The trial will use brain Magnetic Resonance Imaging (MRI) to identify which patients are likely to be within the critical 4.5 hour time window and thus eligible to benefit from the drug.

The majority of strokes are caused when a blood clot cuts off the blood supply to an area of the brain. If the brain tissue is starved of oxygen for too long, brain cells begin to die resulting in permanent damage and potential long-term disability.

Giving tPA to patients soon after stroke symptoms begin can reopen a blocked artery, restoring precious blood flow and reducing the amount of brain damage that results. This treatment is very effective: if tPA is given within 4.5 hours, 10% more people recover fully from a stroke and about a third of treated patients show better functional outcomes than those not given the drug.

The WAKE-UP team, coordinated by Dr Christian Gerloff from the University Medical Center in Hamburg, Germany, have developed the method of using MRI brain imaging to confirm how long ago a stroke began. In a pilot trial of 543 patients with known stroke onset, the WAKE-UP partners found that 80-90% of patients showing a particular MRI imaging pattern had stroke onset within 4.5 hours.

The European Commission has recognized the enormous potential of this diagnostic scan. The team has received almost €12 million to fund a multicentre randomized clinical trial of 800 patients in 40 centres throughout Germany, Belgium, Denmark, UK, France and Spain.

Patients waking up with stroke symptoms and presenting at one on the participating hospitals will be screened with the specific MRI and, if their brain scans show the correct imaging pattern to indicate they are within 4.5 hours from stroke onset, they will be enrolled in the trial. Patients will be randomly assigned to receive either tPA treatment or a placebo drug, and compared to see which group does better in the long term.

If the MRI method can be used to accurately predict start time in patients waking up with stroke, it is estimated that 10,000 more patients a year in Europe would have a complete functional recovery from stroke. Many more patients would endure reduced levels of disability because of access to the emergency tPA treatment.

In the UK the trial is being co-ordinated by Professor Keith Muir of the University of Glasgow, and patients will be enrolled at sites across the country including London, Manchester, and Cambridge. SAFE is a partner in WAKE-UP and will be involved from the outset to ensure the trial protocol complies with patients’ needs.

If the WAKE-UP trial is successful, it has the potential to change medical practice and reduce the burden of stroke in Europe.

For the latest trial updates, visit the WAKE-UP website. An information flyer about the trial can be downloaded here.