Hunter-led advances in acute stroke care will change clinical practice

Dec 3 2013

By Professor Mark Parsons

Professor Mark Parsons

Our Hunter-led, Australian collaborative has made two recent advances that hold promise for a global transformation in acute stroke care.

The first of these is the use of advanced brain imaging to identify potentially salvageable brain tissue – the ischaemic penumbra. The second is our recent discovery in a phase II trial that the new generation intravenous thrombolytic agent, Tenecteplase, provides superior clot-dissolving and clinical outcomes over the current standard thrombolytic, recombinant tissue plasminogen activator (Alteplase).

The standard clot-dissolving agent Alteplase is a proven effective treatment for acute ischaemic stroke – it must be given as soon as possible after onset of stroke symptoms (the latest time it is proven to be of benefit is up to 4.5 hours after stroke).

It works by dissolving the clot blocking an artery to the brain (the cause of ischaemic stroke – the commonest cause of stroke).

However, it works effectively in perhaps only 1 in 3 patients we treat. This is because of two main reasons:

Firstly, Alteplase takes too long to dissolve the clot and this leads to more brain being damaged while the clot remains blocking blood flow to the brain, and secondly, with the standard brain imaging we cannot see how much brain is dead before treatment – thus with the standard brain imaging, we may be treating patients with little chance of benefit as ‘we have missed the boat’.

The HMRI Stroke Group’s new phase III trial is specially designed to target these two problems – using a newer clot-buster that seemed to work a lot more effectively and quickly at unblocking the artery, and using advanced brain imaging that we have been working on over the last decade to bring to routine clinical practice to select patients who have the most to gain from clot-dissolving.

In our phase II study comparing the new drug Tenecteplase to the standard drug we found that Tenecteplase was better at clot-dissolving and this led to more patients with major clinical recovery compared to Alteplase.

Interestingly, we also saw a trend towards less brain bleeding with Tenecteplase than with Alteplase (which is an uncommon, but catastrophic, complication of clot-dissolving treatment). However, our phase II study (published in the New England Journal of Medicine) was quite small and we need to prove this in a larger study before we can be certain that Tenecteplase is a better alternative.

Tenecteplase versus Alteplase for Stroke Thrombolysis Evaluation (TASTE) is a Hunter-conceived and led, investigator initiated, randomised phase III trial designed to generate practice-changing evidence by translating the advanced imaging treatment selection approach used in our recent positive phase II trial.

TASTE aims to confirm the superiority of the genetically modified new-generation plasminogen activator, Tenecteplase, over the standard tissue plasminogen activator, Alteplase, in the broader group of stroke patients eligible for acute thrombolytic treatment in the current time window (less than 4.5 hours after stroke onset).

TASTE will address three crucial clinical and pathophysiologic questions in a much broader group of stroke patients eligible for acute thrombolytic therapy:

  • Does Tenecteplase lead to superior early reperfusion and salvage of the ischaemic penumbra compared to Alteplase?
  • Does the superior early reperfusion seen with Tenecteplase translate into greater early clinical recovery compared to Alteplase?
  • Does Tenecteplase lead to less long-term disability than Alteplase?

A positive study result in TASTE would be applicable to millions of people worldwide, including some 25% of the 30,000+ Australians who present early with acute ischaemic stroke each year, and will undoubtedly directly translate into a major change in clinical practice.