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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Stroke, Acute
• Intervention / Treatment: Other: Mobile Stroke Unit deployment

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 450
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Khaoussou SYLLA, MD, PhD; Phone Number: +33 (01) 45 65 76 78; Email: k.sylla@ghu-paris.fr
• Study Contact Backup: Name: Malha BERRAH, MSc; Phone Number: +33 (0)1 56 09 58 22; Email: malha.berrah@aphp.fr

Study Locations

• France
  • Garches, France, 92380
    • Recruiting
    • AP-HP - Hôpital Raymond Poincaré
    • Contact: Sandrine Deltour, MD; Email: sandrine.deltour@aphp.fr
  • Le Kremlin-Bicêtre, France, 94275
    • Recruiting
    • AP-HP - Hôpital Bicêtre
    • Contact: Christian DENIER, MD, PhD; Phone Number: +33 (0) 145 21 24 03; Email: christian.denier@aphp.fr
  • Paris, France, 75019
    • Recruiting
    • Fondation Ophtalmologique Rothschild
    • Contact: Michaël OBADIA, MD; Phone Number: +33 (0)1 48 03 68 52; Email: mobadia@for.paris
  • Paris, France, 75014
    • Recruiting
    • GHU Paris Psychiatrie & Neurosciences
    • Contact: Guillaume TURC, MD, PhD; Phone Number: +33 (0)1 45 65 85 65; Email: g.turc@ghu-paris.fr
  • Paris, France, 75010
    • Recruiting
    • AP-HP - Hopital Lariboisiere
    • Contact: Mikaël MAZIGHI, MD, PhD; Phone Number: +33 (0)1 49 95 25 97; Email: mmazighi@for.paris
  • Paris, France, 75013
    • Recruiting
    • AP-HP - hôpital de la Pitié-Salpêtrière
    • Contact: Sonia ALAMOWITCH, MD, PhD; Phone Number: +33 (0)1 71 97 06 51; Email: sonia.alamowitch@aphp.fr
  • Paris, France, 75015
    • Recruiting
    • SAMU 75 de Paris
    • Contact: Benoît VIVIEN, MD, PhD; Phone Number: +33 (0)1 44 49 24 75; Email: benoit.vivien@aphp.fr
  • Paris, France, 75017
    • Recruiting
    • BSPP, Brigade des Sapeurs-Pompiers de Paris
    • Contact: Caterina ZAMPIERI, MD; Phone Number: +33 (0)6 51 15 13 42; Email: zampiericaterina@gmail.com
  • Paris, France, 75018
    • Recruiting
    • AP-HP - hôpital Bichat - Claude-Bernard
    • Contact: Phlippa LAVALLEE, MD; Email: philippa.lavallee@aphp.fr
  • Paris, France, 75674
    • Not yet recruiting
    • Hopital Saint Joseph
    • Contact: Mathieu ZUBER, MD, PhD; Phone Number: +33 (0)1 44 12 34 09; Email: mzuber@ghpsj.fr
  • Suresnes, France, 92151
    • Recruiting
    • Hopital Foch
    • Contact: Bertrand LAPERGUE, MD; Phone Number: +33 (1) 46 25 59 73; Email: b.lapergue@hopital-foch.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention (MSU); Deployment of MSU + conventional ambulance	Other: Mobile Stroke Unit deployment; 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).; Other Names: Mobile Stroke Unit management
No Intervention: Control (usual care); Deployment of conventional ambulance

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Centre Hospitalier St Anne
• Collaborators: Assistance Publique - Hôpitaux de Paris; Ministry of Health, France
• Investigators: Principal Investigator: Guillaume TURC, MD, PhD, GHU Paris Psychiatrie et Neurosciences; Study Director: Benoît VIVIEN, MD, PhD, APHP - Centre Hospitalier Universitaire Necker

Publications and helpful links

General Publications

• Turc G, Hadziahmetovic M, Walter S, Churilov L, Larsen K, Grotta JC, Yamal JM, Bowry R, Katsanos AH, Zhao H, Donnan G, Davis SM, Hussain MS, Uchino K, Helwig SA, Johns H, Weber JE, Nolte CH, Kunz A, Steiner T, Sacco S, Ebinger M, Tsivgoulis G, Fassbender K, Audebert HJ. Comparison of Mobile Stroke Unit With Usual Care for Acute Ischemic Stroke Management: A Systematic Review and Meta-analysis. JAMA Neurol. 2022 Mar 1;79(3):281-290. doi: 10.1001/jamaneurol.2021.5321.

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2023
• Primary Completion (Estimated): October 16, 2026
• Study Completion (Estimated): June 16, 2027

Study Registration Dates

• First Submitted: December 2, 2022
• First Submitted That Met QC Criteria: December 12, 2022
• First Posted (Actual): December 14, 2022

Study Record Updates

• Last Update Posted (Actual): February 1, 2024
• Last Update Submitted That Met QC Criteria: January 31, 2024
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Cost-effectiveness; Cost-utility; Mechanical thrombectomy; Intravenous thrombolysis; Mobile Stroke Unit; MSU; Emergency Medical Service
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke
• Other Study ID Numbers: 2018-A02567-48; PRME 15-0677 (Other Grant/Funding Number: French Ministry of Health)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data (IPD) could be available to other researcher aiming to conduct an IPD-meta analysis of studies of MSU vs. usual care (please see access criteria below).
• IPD Sharing Time Frame: Two years after the last publication
• IPD Sharing Access Criteria: Data sharing must be accepted by the sponsor and the PI based on a scientific project and scientific involvement of the PI team. Collaboration will be fostered. Data sharing must respect the agreements made with funders. Teams wishing to obtain IPD must meet the sponsor and PI team to present scientific (and commercial) purpose, IPD needed, format of data transmission, and time frame. Technical feasibility and financial support will be discussed before mandatory contractual agreement. Processing of shared data must comply with European General Data Protection Regulation (GDPR).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No