ESJ Featured Article of the Month – September 2025: Results of the PRACTISE Trial

This month in the European Stroke Journal, Keith Muir and colleagues present the results of the PRACTISE trial.

This randomised controlled trial sought to compare two different acute stroke imaging approaches (non-contrast CT compared to multimodal CT which included CT angiogram and CT perfusion ) and to assess the influence of initial imaging on thrombolysis rates.

When this trial was conceived, the hypothesis was that the addition of CTA and CTP would increase the likelihood of receiving thrombolytic treatment within 4.5 hours, by identifying more patients with vessel occlusion or perfusion mismatch who would not otherwise have been identified by NCCT. This trial would also be able to tackle the question of whether performing advanced imaging in addition to NCCT delays the time to decision and the door to needle time.

The PRACTISE trial was conducted from March 2015 to May 2018 at 11 UK sites, all of which were established thrombolysis centres participating in the national UK stroke audit and with prior experience of multimodal imaging. The study recruited adult patients presenting with signs and symptoms consistent with acute ischaemic stroke within 4.5 hours of symptom onset, who were potentially eligible for thrombolysis. All patients provided informed consent. Included patients were randomised in a 1:1 ratio to either non-contrast CT (NCCT) or multimodal CT (NCCT+CTA +CTP). If the initial NCCT identified a contraindication to thrombolysis such as intracranial haemorrhage, the patient was regarded as a screen failure and was excluded from the study. All scans were analysed locally at the participating hospital site and treatment decisions made by the local treating physician according to current UK guidelines. The trial also collected the imaging data and centrally analysed the results to assess agreement with the treating sites.

In total, 271 patients were randomised, 134 to multimodal CT and 137 to NCCT. Recruitment was ceased after funding became unavailable. The original sample size calculation estimated that 200 subjects per group was required to detect an increase in the proportion treated with thrombolysis from 25% to 40% (an absolute change of 15%), with a power of 80%, allowing for post randomisation exclusions for non-stroke pathology. This means that the trial is underpowered to definitively answer its primary aim.

After initial imaging was performed, 49 of the 271 patients were excluded due to contraindications for thrombolysis- the most common reasons were intracerebral haemorrhage (in 24) and non-stroke pathology (in 10). There were 114 remaining thrombolysis eligible patients in the multimodal CT arm and 108 in the NCCT arm. The average age of participants was 67.5 years, and 45.6% were women. The median NIHSS score was 6 (IQR 3-12). The median time to randomisation was 122 minutes (IWR 90-165). Of those randomised to receive multimodal CT, 94% had CTA performed and 91% had CTP. Of those randomised to receive NCCT alone, 17% also received CTA, but none received CTP.

The primary outcome of this trial was the proportion receiving thrombolysis. Overall 57.7% of patients included in this trial received thrombolysis. Less patients receiving multimodal CT (56/114, 49.1%) received IV thrombolysis compared to those receiving NCCT (73/108, 67.6%); adjusted odds ratio 0.46 (95% CI 0.25-0.83, p=0.01). This was the opposite direction of effect to what the investigators originally hypothesised.

Importantly, the time from symptom-onset to treatment decision did not differ between the two imaging strategies: in the multimodal group the median was 131minutes (IQR 116-180) and 135 minutes (IQR 108-170) for the NCCT group (p=0.64). Neither was there a difference in onset to needle time: 144 minutes (IQR120-184) for the multimodal CT arm compared with 145 minutes (IQR 118-174) for the NCCT arm. Additionally, there was no difference in functional outcome (measured by modified Rankin scale) between imaging strategies. There were numerically less deaths in those receiving multimodal CT (6/114 [5.3%]) compared to those receiving NCCT (11/108, [10.2%], p=0.2).

Some imaging findings were strongly associated with an increased likelihood of receiving thrombolysis including ASPECTS score <10, presence of intracranial occlusion identified on CTA or the presence of a perfusion mismatch on CTP. Every patient with CTP mismatch identified in this trial received thrombolysis. Conversely, 51 patients were not treated based on the results of advanced imaging as there was no evidence of vessel occlusion, of acute ischaemic change or of perfusion mismatch. Patients who did not receive thrombolysis in this trial had a lower median NIHSS score of 4, and were more likely to have isolated or mild symptoms. This is the first trial to randomise patients to NCCT or multimodal CT imaging in the acute phase of stroke within the 4.5 hour window for thrombolysis. Multimodal CT was associated with reduced thrombolysis treatment rates, but without evidence of a time delay in treatment or differences in functional outcomes. Additionally, there were numerically fewer intracerebral haemorrhages and deaths in those receiving multimodal CT. It is likely that appropriate exclusion of stroke mimics was one factor in the results of this trial. In the UK stroke audit, stroke mimics were estimated to account for 31% of all acute presentations to hospital services and up to half of all stroke assessments performed. While the risk of intracerebral haemorrhage occurring when thrombolysis is given to a patient with a stroke mimic is lower than for acute ischaemic stroke, it still occurs in about 1% of cases, with potentially serious or fatal consequences. Furthermore, the authors observe that the additional time taken to perform multimodal imaging was offset by a slightly shorter treatment decision time as the decision making was often less complex after incorporating additional information based on the results of  CTA and CTP. This trial suggests that widespread use of multimodal CT to assess patients with suspected acute ischaemic stroke within 4.5 hours of onset, who are eligible for thrombolysis would reduce thrombolysis treatment rates, but may increase the accuracy of treatment decisions – meaning thrombolysis treatment is better targeted at patients most likely to benefit. Further analysis is needed to calculate potential cost savings due to reduced thrombolysis use and lower number of complications balanced against the increased cost and resource implications of more widespread scanning. It is worth remembering that this study did not recruit to full sample size planned by the power calculation due to lack of funding. Additionally, functional outcomes were not the primary outcome of this trial, and a further trial would be required to confirm that there is truly no difference in functional outcome associated with different imaging modalities. Nevertheless it is interesting to observe that the direction of effect is opposite to what the investigators had hypothesised, but more data is needed to confirm this finding. _ [/av_textblock] [/av_one_full][av_hr class='full' icon_select='yes' icon='ue808' font='entypo-fontello' position='center' shadow='shadow' height='50' custom_border='av-border-thin' custom_width='50px' custom_margin_top='30px' custom_margin_bottom='30px' custom_border_color='' custom_icon_color='' id='' custom_class='' template_class='' av_uid='av-lzcfp5ms' sc_version='1.0' admin_preview_bg=''] [av_one_full first min_height='' vertical_alignment='av-align-top' space='' row_boxshadow='' row_boxshadow_color='' row_boxshadow_width='10' custom_margin='' margin='0px' mobile_breaking='' min_col_height='' padding='' svg_div_top='' svg_div_top_color='#333333' svg_div_top_width='100' svg_div_top_height='50' svg_div_top_max_height='none' svg_div_top_flip='' svg_div_top_invert='' svg_div_top_front='' svg_div_top_opacity='' svg_div_top_preview='' svg_div_bottom='' svg_div_bottom_color='#333333' svg_div_bottom_width='100' svg_div_bottom_height='50' svg_div_bottom_max_height='none' svg_div_bottom_flip='' svg_div_bottom_invert='' svg_div_bottom_front='' svg_div_bottom_opacity='' svg_div_bottom_preview='' border='' border_style='solid' border_color='' radius='' column_boxshadow='' column_boxshadow_color='' column_boxshadow_width='10' background='bg_color' background_color='' background_gradient_direction='vertical' background_gradient_color1='#000000' background_gradient_color2='#ffffff' background_gradient_color3='' src='' background_position='top left' background_repeat='no-repeat' highlight='' highlight_size='' animation='' link='' linktarget='' link_hover='' title_attr='' alt_attr='' mobile_display='' id='' custom_class='' template_class='' aria_label='' av_uid='av-k8ge8i' sc_version='1.0'] [av_textblock fold_type='' fold_height='' fold_more='Read more' fold_less='Read less' fold_text_style='' fold_btn_align='' textblock_styling_align='' textblock_styling='' textblock_styling_gap='' textblock_styling_mobile='' size='' av-desktop-font-size='' av-medium-font-size='' av-small-font-size='' av-mini-font-size='' font_color='' color='' fold_overlay_color='' fold_text_color='' fold_btn_color='theme-color' fold_btn_bg_color='' fold_btn_font_color='' size-btn-text='' av-desktop-font-size-btn-text='' av-medium-font-size-btn-text='' av-small-font-size-btn-text='' av-mini-font-size-btn-text='' fold_timer='' z_index_fold='' id='' custom_class='' template_class='' av_uid='av-lbnj6g9h' sc_version='1.0' admin_preview_bg=''] ESOC is Europe’s leading forum for advances in research and clinical care of patients with cerebrovascular diseases. 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