Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: a randomized controlled trial

Randomised, controlled, multicentre, open label trial with blinded follow up determining the clinical efficacy of intra-arterial prourokinase in patients with acute stroke caused by occlusion of the middle cerebral artery. Only those patients for whom treatment could be initiated within six hours of the onset of symptoms were included. A total of 180 patients were recruited, all of whom passed computed tomography (CT) and cerebral angiography criteria, and were randomised to receive either intra-arterial prourokinase and intravenous heparin or intravenous heparin alone. A second angiogram was performed at two hours and CT scans were performed at baseline, 24 hours and 7 to 10 days after initial treatment. The primary outcome, defined by a modified Rankin score (a score of disability), was the proportion of patients with slight or no neurological disability at 90 days. Secondary outcomes included MCA recanalisation, frequency of intracranial haemorrhage and mortality.

Results showed better neurological outcome in the treatment group with 40% of prourokinase patients and 25% of controls having a modified Rankin score of 2 or less at 90 days. Intracranial haemorrhage with neurological deterioration occurred in 10% of prourokinase patients and 2% of controls, but overall mortality was essentially equal, with 25% and 27% in the respective groups.

Critique—There is a great deal of interest in the role of thrombolysis in acute ischaemic stoke. The evidence so far seems to indicate that neurological outcome can be improved if the treatment is given early but with a real increased risk of intracranial haemorrhage. Intravenous thrombolysis seems to have benefit only if given within three hours of onset of symptoms. The PROACT II trial achieved its goal of demonstrating the possibility of extending the therapeutic window to six hours by the use of intra-arterial injection. …