Multimodal versus non-contrast computed tomography for assessment of acute ischaemic stroke: the PRACTISE RCT

Background Non-contrast computed tomography has low sensitivity to brain ischaemia. Higher sensitivity of computed tomography perfusion and computed tomography angiography may identify more thrombolysis-eligible patients, but the role of these imaging modalities in thrombolysis treatment decisions within 4.5 hours is unclear. We hypothesised that multimodal computed tomography (non-contrast computed tomography + computed tomography angiography + computed tomography perfusion) would modify treatment decisions with net increase in thrombolysis rates. Design Prospective, randomised controlled clinical trial. Setting Hospital acute stroke services. Participants Adults with clinically suspected acute ischaemic stroke eligible for intravenous thrombolytic therapy. Interventions 1 : 1 randomisation to non-contrast computed tomography or multimodal imaging (non-contrast computed tomography + computed tomography angiography + computed tomography perfusion). Main outcome measures Proportion treated with intravenous thrombolytic therapy (primary outcome). Secondary end points: functional recovery at 3 months, early neurological recovery, times to decision making and treatment delivery, safety (mortality, incidence of symptomatic intracerebral haemorrhage). Results Over 36 months, 11 United Kingdom sites randomised 271 patients (134 multimodal computed tomography, 137 non-contrast computed tomography). The mean age was 67.6 years and the median National Institutes of Health Stroke Scale score was 6 (interquartile range 3–12). After initial non-contrast computed tomography, 114/134 multimodal computed tomography and 108/137 non-contrast computed tomography patients were found to be thrombolysis-eligible. Significantly fewer multimodal computed tomography patients received thrombolytic therapy (56/114, 49.1%) compared to non-contrast computed tomography alone [73/108, 67.6%, odds ratio 0.46 (95% confidence interval: 0.25 to 0.83), p = 0.0102]. Treatment decision and delivery times, early neurological recovery and day 90 functional outcomes did not differ significantly between groups. Mortality was 6/114 (5.3%) in the multimodal computed tomography group and 11/108 (10.2%) in non-contrast computed tomography alone [odds ratio 0.46 (95% confidence interval: 0.16 to 1.31), p = 0.147]. Symptomatic intracerebral haemorrhage occurred in two patients, both in the non-contrast computed tomography group. There were no significant interactions between stroke subgroups by severity or syndrome. The proportion of patients with confirmed stroke on follow-up imaging at 24 hours did not differ significantly between groups. Limitations Recruitment was lower than the planned sample size, but thrombolysis rate was much higher than originally estimated (60% overall vs. 25% estimated). Computed tomography interpretation and treatment decisions were at the discretion of clinicians. Findings reflect United Kingdom practice in a predominantly less severe stroke clinical population. Conclusions Multimodal computed tomography resulted in significantly fewer patients receiving thrombolysis, principally because multimodal imaging did not identify relevant therapeutic targets (perfusion defects or intracranial vessel occlusion). Treatment decision times and clinical outcomes did not differ significantly between groups. Fewer deaths and no symptomatic intracerebral haemorrhages occurred in the multimodal computed tomography group. Future work Further investigation of potentially lower mortality and symptomatic intracerebral haemorrhage with multimodal imaging is of potential clinical importance. Trial registration This trial is registered as ClinicalTrials.gov identifier NCT02360670. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 11/100/78) and is published in full in Efficacy and Mechanism Evaluation ; Vol. 12, No. 6. See the NIHR Funding and Awards website for further award information.