Optimising clinical trial design for proof of neuroprotection in acute ischaemic stroke: The SAINT clinical trial programme

The development of effective therapies for acute ischaemic stroke has proven to be a challenging task. The only approved therapy for acute ischaemic stroke remains intravenous recombinant tissue plasminogen activator initiated within 3 h of stroke onset, following a CT scan to exclude intracerebral haemorrhage. Many other therapies have been evaluated in Phase III clinical trials, including more than 50 neuroprotective agents, but the results have either been inconclusive or negative. These trials have provided valuable lessons for the design of future studies in acute ischaemic stroke, including the importance of adequate testing in preclinical studies, time to treatment from symptom onset, target dose, patient selection, sample size and the outcome measures used. These key criteria have been captured in the Stroke Therapy Academic Industry Roundtable (STAIR) recommendations for the preclinical and clinical development of acute stroke therapies. NXY-059 is a novel free radical-trapping neuroprotectant that reduces infarct size and preserves brain function in animal models of acute ischaemic stroke. It is one of the first compounds to have progressed to Phase III clinical trials, having fulfilled the STAIR recommendations for the preclinical development of neuroprotective agents. The efficacy and safety of NXY-059 in patients with acute ischaemic stroke is currently being evaluated in the Stroke Acute Ischaemic NXY-059 Treatment (SAINT) clinical trial programme, which was designed in accordance with the STAIR clinical recommendations. The final results from the first of these studies, SAINT I, have recently been reported.