Comparison of tenecteplase with alteplase for the early treatment of ischaemic stroke in the Melbourne Mobile Stroke Unit (TASTE-A): a phase 2, randomised, open-label trial.

BACKGROUND: Mobile stroke units (MSUs) equipped with a CT scanner reduce time to thrombolytic treatment and improve patient outcomes. We tested the hypothesis that tenecteplase administered in an MSU would result in superior reperfusion at hospital arrival, when compared with alteplase. METHODS: The TASTE-A trial is a phase 2, randomised, open-label trial at the Melbourne MSU and five tertiary hospitals in Melbourne, VIC, Australia. Patients (aged ≥18 years) with ischaemic stroke who were eligible for thrombolytic treatment were randomly allocated in the MSU to receive, within 4·5 h of symptom onset, either standard-of-care alteplase (0·9 mg/kg [maximum 90 mg], administered intravenously with 10% as a bolus over 1 min and 90% as an infusion over 1 h), or the investigational product tenecteplase (0·25 mg/kg [maximum 25 mg], administered as an intravenous bolus over 10 s), before being transported to hospital for ongoing care. The primary outcome was the volume of the perfusion lesion on arrival at hospital, assessed by CT-perfusion imaging. Secondary safety outcomes were modified Rankin Scale (mRS) score of 5 or 6 at 90 days, symptomatic intracerebral haemorrhage and any haemorrhage within 36 h, and death at 90 days. Assessors were masked to treatment allocation. Analysis was by intention-to-treat. The trial was registered with ClinicalTrials.gov, NCT04071613, and is completed. FINDINGS: Between June 20, 2019, and Nov 16, 2021, 104 patients were enrolled and randomly allocated to receive either tenecteplase (n=55) or alteplase (n=49). The median age of patients was 73 years (IQR 61-83), and the median NIHSS at baseline was 8 (5-14). On arrival at the hospital, the perfusion lesion volume was significantly smaller with tenecteplase (median 12 mL [IQR 3-28]) than with alteplase (35 mL [18-76]; adjusted incidence rate ratio 0·55, 95% CI 0·37-0·81; p=0·0030). At 90 days, an mRS of 5 or 6 was reported in eight (15%) patients allocated to tenecteplase and ten (20%) patients allocated to alteplase (adjusted odds ratio [aOR] 0·70, 95% CI 0·23-2·16; p=0·54). Five (9%) patients allocated to tenecteplase and five (10%) patients allocated to alteplase died from any cause at 90 days (aOR 1·12, 95% CI 0·26-4·90; p=0·88). No cases of symptomatic intracerebral haemorrhage were reported within 36 h with either treatment. Up to day 90, 13 serious adverse events were noted: five (5%) in patients treated with tenecteplase, and eight (8%) in patients treated with alteplase. INTERPRETATION: Treatment with tenecteplase on the MSU in Melbourne resulted in a superior rate of early reperfusion compared with alteplase, and no safety concerns were noted. This trial provides evidence to support the use of tenecteplase and MSUs in an optimal model of stroke care. FUNDING: Melbourne Academic Centre for Health.

Tenecteplase versus Alteplase for Stroke Thrombolysis Evaluation Trial in the Ambulance (Mobile Stroke Unit-TASTE-A): protocol for a prospective randomised, open-label, blinded endpoint, phase II superiority trial of tenecteplase versus alteplase for ischaemic stroke patients presenting within 4.5 hours of symptom onset to the mobile stroke unit.

INTRODUCTION: Mobile stroke units (MSUs) equipped with a CT scanner are increasingly being used to assess and treat stroke patients' prehospital with thrombolysis and transfer them to the most appropriate hospital for ongoing stroke care and thrombectomy when indicated. The effect of MSUs in both reducing the time to reperfusion treatment and improving patient outcomes is now established. There is now an opportunity to improve the efficacy of treatment provided by the MSU. Tenecteplase is a potent plasminogen activator, which may have benefits over the standard of care stroke lytic alteplase. Specifically, in the MSU environment tenecteplase presents practical benefits since it is given as a single bolus and does not require an infusion over an hour like alteplase. OBJECTIVE: In this trial, we seek to investigate if tenecteplase, given to patients with acute ischaemic stroke as diagnosed on the MSU, improves the rate of early reperfusion. METHODS AND ANALYSIS: TASTE-A is a prospective, randomised, open-label, blinded endpoint (PROBE) phase II trial of patients who had an ischaemic stroke assessed in an MSU within 4.5 hours of symptom onset. The primary endpoint is early reperfusion measured by the post-lysis volume of the CT perfusion lesion performed immediately after hospital arrival. ETHICS AND DISSEMINATION: The study was approved by the Royal Melbourne Hospital Human Ethics committee. The findings will be published in peer-reviewed journals, presented at academic conferences and disseminated among consumer and healthcare professional audiences. TRIAL REGISTRATION NUMBER: NCT04071613.

SCIPA Full-On: A Randomized Controlled Trial Comparing Intensive Whole-Body Exercise and Upper Body Exercise After Spinal Cord Injury.

Background. While upper body training has been effective for improving aerobic fitness and muscle strength after spinal cord injury (SCI), activity-based therapies intended to activate the paralyzed extremities have been reported to promote neurological improvement. Objective. To compare the effectiveness of intensive whole-body exercise compared with upper body exercise for people with chronic SCI. Methods. A parallel-group randomized controlled trial was conducted. Participants with a range of SCI levels and severity were randomized to either full-body exercise (FBE) or upper body exercise (UBE) groups (3 sessions per week over 12 weeks). FBE participants underwent locomotor training, functional electrical stimulation-assisted leg cycling, and trunk and lower extremity exercises, while UBE participants undertook upper body strength and aerobic fitness training only. The primary outcome measure was the American Spinal Injury Association (ASIA) motor score for upper and lower extremities. Adverse events were systematically recorded. Results. A total of 116 participants were enrolled and included in the primary analysis. The adjusted mean between-group difference was -0.04 (95% CI -1.12 to 1.04) for upper extremity motor scores, and 0.90 (95% CI -0.48 to 2.27) for lower extremity motor scores. There were 15 serious adverse events in UBE and 16 in FBE, but only one of these was definitely related to the experimental intervention (bilateral femoral condyle and tibial plateau subchondral fractures). No significant between-group difference was found for adverse events, or functional or behavioral variables. Conclusions. Full-body training did not lead to improved ASIA motor scores compared with upper body training in people with chronic SCI.

Testing a systematic approach to identify and prioritise barriers to successful implementation of a complex healthcare intervention.

BACKGROUND: Multiple barriers may inhibit the adoption of clinical interventions and impede successful implementation. Use of standardised methods to prioritise barriers to target when selecting implementation interventions is an understudied area of implementation research. The aim of this study was to describe a method to identify and prioritise barriers to the implementation of clinical practice elements which were used to inform the development of the T3 trial implementation intervention (Triage, Treatment [thrombolysis administration; monitoring and management of temperature, blood glucose levels, and swallowing difficulties] and Transfer of stroke patients from Emergency Departments [ED]). METHODS: A survey was developed based on a literature review and data from a complementary trial to identify the commonly reported barriers for the nine T3 clinical care elements. This was administered via a web-based questionnaire to a purposive sample of Australian multidisciplinary clinicians and managers in acute stroke care. The questionnaire addressed barriers to each of the nine T3 trial clinical care elements. Participants produced two ranked lists: on their perception of: firstly, how influential each barrier was in preventing clinicians from performing the clinical care element (influence attribute); and secondly how difficult the barrier was to overcome (difficulty attribute). The rankings for both influence and difficulty were combined to classify the barriers according to three categories ('least desirable', desirable' or 'most desirable' to target) to assist interpretation. RESULTS: All invited participants completed the survey; (n = 17; 35% medical, 35% nursing, 18% speech pathology, 12% bed managers). The barriers classified as most desirable to target and overcome were a 'lack of protocols for the management of fever' and 'not enough blood glucose monitoring machines'. CONCLUSIONS: A structured decision-support procedure has been illustrated and successfully applied to identify and prioritise barriers to target within an implementation intervention. This approach may prove to be a useful in other studies and as an adjunct to undertaking barrier assessments within individual sites when planning implementation interventions.