Third International Stroke Trial: IST-3

Strokes are a major cause of disability. Most strokes are due a blood clot blocking an artery in the brain. We know that the ?clot busting? drug rt-PA, given to a person with a stroke within the first 2 or 3 hours of start of the symptoms, can improve their chances of both being alive and not being disabled from the stroke.
But, we know much less about the benefits in older people and in people who only get to hospital more than 3 hours after the symptoms began.
To find out if more patients with stroke could benefit from this treatment, we are a performing a clinical trial. It will involve several thousand people from around the world. Patients who recognise that their symptoms could be a stroke and get to hospital quickly enough will be asked to help with the study.
If the study establishes that a wider variety of patients can be treated, millions of people with stroke worldwide could benefit.

IST-3 is an international, multi-centre, randomised, controlled trial of iv rt-PA (0.9 mg/kg) within 6 hours of onset of acute ischaemic stroke. All potential patients must be assessed and have brain imaging without delay. CT scanning is the prime imaging modality, but CT perfusion/ CT angiography, MRI DWI/PWI/angiography and transcranial doppler can be used as additional selection criteria in centres which participate in the IST3 imaging substudy. Patients who meet clinical and brain imaging criteria are entered by means of a telephone call to a fast centralised computer system which records baseline data, balances on key prognostic factors and allocates treatment. Follow-up is conducted by postal or telephone questionnaire, independently of the clinician treating the patient. The primary measure of outcome is the proportion of patients who are dead or dependent at six months (poor functional outcome). The trial involves innovative methods to make a large scale trial feasible. The web-based CT reading tool developed in the start-up phase is already being applied in several other imaging research projects. The trial builds on our NHS HTA formal economic modelling exercise and will provide reliable evidence on the place of this controversial treatment in routine clinical practice in the NHS (and other publicly funded Health Services). The trial will also provide important - and much needed - randomised trial data on the balance of risk and benefit of this treatment in older people, who have been deliberately excluded from earlier trials of thrombolysis.