MSUs have proven to be a valuable research platform. The usefulness of several biomarkers has been investigated from prehospital blood samples drawn in a specialized stroke ambulance. New imaging software has also been tested in these ambulances. Dedicated teams, specialized in stroke care and with a strong research background will make the best use of MSUs for further research.MSUs offer additional potentials to improve functional outcomes such as by prehospital reversal of oral anticoagulation or ultra-early blood pressure lowering in cases of ICH. But ultimate proof of improved outcome in patients treated in MSUs is still lacking. PRESTO is determined to close this important knowledge gap in the near future.
Several research collaborations were envisioned during the first PRESTO meetings. The following PRESTO-wide initiatives were suggested by the Steering Committee or members, and then agreed upon by unanimous vote of attendees based on their perception of feasibility, impact and fundability.
1. The researchers of the four ongoing or planned controlled trials plan to merge their data to increase statistical power and allow for further analyses. Minimal data sets will be agreed including joint definitions of functional outcomes.
2. In addition, the entire PRESTO group intends to enter all stroke patients in a joint registry using this minimal data set.
3. At least two prehospital studies on diagnosis and treatment of ICH are planned to investigate the ultra-early dynamics of hematoma expansion and the effects of prehospital blood pressure control and reversal of oral anticoagulation.
4. The PRESTO partners will consider joint studies on biomarkers in hyperacute stroke. These studies will both investigate the accuracy of known biomarkers (such as glial fibrillary acidic protein) and search for new biomarkers that can help to identify stroke mimics or differentiate ischemic and hemorrhagic strokes.
5. Finally, the PRESTO members will collaborate in future industry-sponsored studies by acting as a collaborative research group.7
In addition to research already identified above, broader scale research is already underway or envisioned orchestrated by individual PRESTO sites. For instance, the ‘‘BEnefits of Stroke Treatment Using a Mobile Stroke Unit Compared to Standard Management (BEST-MSU)’’ study is a prospective multi-centered cluster randomized (by weeks) comparative effectiveness study investigating outcomes and cost/benefits of MSU implementation compared to Standard Management in the US. This study is designed to minimize bias by enrolling patients as similarly as possible on MSU vs. control weeks, and adjudicating all patients’ study eligibility by an independent investigator blinded to MSU vs. control group assignment. All patients will be followed for a full year to gather data on resource utilization and costs. Finally, outcomes are patient-centered including quality of life, and modified Rankin score weighted by utility scores derived from actual patient preferences. Enrollment of over 900 tPA-eligible patients is planned with over 350 enrolled to date (www.ClinicalTrials.gov NCT02190500). The study is expected to take 4–5 years to complete including 1 year follow-up of all patients.
The ‘‘Berlin-Prehospital Or Usual Care Delivery (B_PROUD)’’ study in Germany is a prospective quasi-randomized study (allocation according to availability of the Berlin STEMOs) that will include all patients who have focal neurological symptoms at arrival of first EMS vessel, a final diagnosis of ischemic stroke or TIA and no contra-indication to either thrombolysis or ET. These selection criteria will avoid bias of different stroke severity scores in both arms as a consequence of differing assessment times. Enrollment of approximately 1500 treatment candidates is planned over a 2–3 years period including 3 months blinded follow-up assessment (www.ClinicalTrials.gov NCT02869386).
The ‘‘Acute Stroke: Prehospital versus in-HospitAL initiation of recanalization Therapy’’ (ASPHALT) study will be a randomized controlled trial of MSU deployment versus standard care, aiming to assess the cost-utility of an MSU for stroke management in the era of bridging therapy. Randomization will be performed on an individual patient basis. Two geographic areas in France will be involved. 450 acute ischemic stroke patients will be recruited over a 3-year period expected to start in 2017, with a blinded follow-up of one year.
A German study on use of MSUs in a rural region (‘‘Mobile Stroke Unit-Concept for Delivery of Specialized Acute Stroke Care to Patients in Remote Areas’’) aims to provide further evidence on the use in such a setting, which requires further definition. The study will be week-wise randomized and include 250 patients (www.ClinicalTrials.gov NCT02465346). Grants for funding are submitted.
While the described studies are not run under the umbrella of PRESTO, PRESTO endorses the studies, and PRESTO members are invited to submit collaborative research ideas to study leaderships. A pooled analysis of the studies is planned in order to increase statistical power and enable subgroup analyses. It is hoped that emanating from the ICH studies already described, PRESTO will help organize an international collaborative study using PRESTO member MSUs as a platform to test ultra-early interventional treatment in ICH patients. As an example, there is interest in a collaborative trial of hemostatic therapy with tranexamic acid, to attenuate hematoma growth.