Acute Stroke: Prehospital Versus In-HospitAL Initiation of Recanalization Therapy- ASPHALT

Study Overview
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Brief Summary
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ASPHALT is an academic-driven open-label randomized controlled trial of Mobile Stroke Unit (MSU) deployment versus standard care in France, with blinded assessment of efficacy endpoints. 450 patients with confirmed acute ischemic stroke will be recruited over a 3-year period, with 3-month follow-up.

Detailed Description
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Instead of the traditional approach of waiting until the patient arrives at the hospital to perform brain imaging and start reperfusion therapies, mobile stroke units (MSUs; ambulances equipped with a CT scanner) now allow pre-hospital initiation of intravenous thrombolysis (IVT). Two large non-randomized clinical trials (B_PROUD & BEST-MSU) have recently shown that MSU use leads to improved functional outcomes at 3 months in specific settings. However, MSUs have been criticized because of their cost and a lack of evidence of a significant reduction in the time between symptom onset and mechanical thrombectomy, which is the cornerstone of treatment of patients with large vessel occlusion. We hypothesized that compared to usual care, the deployment of a MSU would result in an incremental cost-utility ratio ≤50,000 euros per QALY in the lifetime horizon, even in an area with many thrombectomy-capable centers.. Academic-driven open-label randomized controlled trial of Mobile Stroke Unit (MSU) deployment versus standard care in France, with blinded assessment of efficacy endpoints. Randomization will be performed on an individual patient basis (randomization of MSU deployment at dispatch). 450 patients with confirmed acute ischemic stroke (emergency call ≤6 hours after onset) will be recruited over a 3-year period, with 3-month follow-up. Costs and clinical outcomes will be collected prospectively during the study period and used to extrapolate the incremental cost-utility ratio over a lifetime horizon.

Official Title
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Prehospital Initiation of Reperfusion Therapy for Acute Ischemic Stroke: Randomized Medico-economic Evaluation of a Mobile Stroke Unit.

Conditions
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Stroke, Acute

Intervention / Treatment
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* Other: Mobile Stroke Unit deployment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Emergency call to one of the two following emergency medical service (EMS) dispatch centers : SAMU (Service d'Aide Médicale Urgente) or BSPP (Brigade des Sapeurs Pompiers de Paris), between 08:00 and 18:00, 5 days a week (Monday to Friday). Suspected acute stroke according to a dispatcher stroke identification algorithm, adapted from the ROSIER scale Symptom onset-to-randomization time ≤ 6h Patient located within the predefined catchment area of the MSU MSU available at the time of the EMS call Informed consent (as approved by the ethics committee, informed consent will be obtained after randomization: at the arrival of the MSU (intervention group), or at hospital arrival (control group)) Exclusion Criteria: Patient confined to be more than 50% of waking hours Unknown or uncertain onset time (e.g. wake-up stroke) Medical history of epilepsy Recent epileptic seizure (<12 hrs) Suspicion of pregnancy Parturient or breastfeeding woman Patient already participating in another interventional study, which could influence the mRS at 3 months. Patient under guardianship or curatorship Patient not affiliated to French Social Security

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized controlled trial, PROBE design
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention (MSU)<br>Deployment of MSU + conventional ambulance | Other: Mobile Stroke Unit deployment<br>* Deployment of an MSU + conventional ambulance, allowing prehospital CT-scan imaging with intracranial CT angiography. This will allow prehospital intravenous thrombolysis and optimal triage (i.e. accurate identification of patients with large vessel occlusion, who are eligible for mechanical thrombectomy).<br>* Other names: Mobile Stroke Unit management;|
| No Intervention: Control (usual care)<br>Deployment of conventional ambulance | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incremental Cost-Utility Ratio (ICUR) | ICUR in the lifetime horizon, based on extrapolated results of the Modified Rankin Scale (mRS) at 3 months and incremental costs prospectively collected during the first 3 months | 3 months | 
| Key secondary outcome: Modified Rankin Scale (mRS) at 3 months | Modified Rankin scale, assessed in a blinded fashion (range, 0 to 6, with 0 indicating no disability, 3 indicating moderate disability, and 6 indicating death) | 90 +/- 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ICUR at 3 months | Incremental Cost-Utility Ratio based on results of the Modified Rankin Scale (mRS) at 3 months and incremental costs prospectively collected during the first 3 months | 90 +/- 14 days | 
| ICUR at 5 years | Incremental Cost-Utility Ratio based on extrapolated results of the Modified Rankin Scale (mRS) at 3 months and incremental costs prospectively collected during the first 3 months | 5 years | 
| Time from symptom onset to intravenous thrombolysis (IVT) | Time from symptom onset to IVT bolus | up to 4.5 hours from symptom onset | 
| Time from symptom onset to mechanical thrombectomy (MT) | Time from symptom onset to arterial puncture | up to 24 hours from symptom onset | 
| Time from alarm to IVT | Time from ambulance dispatch to IVT bolus | up to 4.5 hours from symptom onset | 
| Time from alarm to MT | Time from ambulance dispatch to arterial puncture | up to 24 hours from symptom onset | 
| Death within 3 months after randomization | All-cause mortality | Within 90 days after randomization | 
| Death within 7 days after randomization | All-cause mortality | Within 7 days after randomization | 
| Proportion of ischemic stroke patients treated with IVT | Proportion of patient treated with IVT among those with confirmed ischemic stroke | up to 4.5 hours from symptom onset | 
| Proportion of ischemic stroke patients with MT | Proportion of patient treated with MT among those with confirmed ischemic stroke | up to 24 hours from symptom onset | 
| Proportion of ischemic stroke patients treated with IVT within 60 minutes of symptom onset | Golden hour thrombolysis | within 60 minutes of symptom onset | 
| Symptomatic intracranial hemorrhage | ECASS-2 definition | Within 36 hours from randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mobile Stroke Unit, MSU, Intravenous thrombolysis, Emergency Medical Service, Mechanical thrombectomy, Cost-utility, Cost-effectiveness