Effect of Direct Transportation to Thrombectomy-Capable Center vs Local Stroke Center on Neurological Outcomes in Patients With Suspected Large-Vessel Occlusion Stroke in Nonurban Areas: The RACECAT Randomized Clinical Trial

Abstract

Importance: In nonurban areas with limited access to thrombectomy-capable centers, optimal prehospital transport strategies in patients with suspected large-vessel occlusion stroke are unknown.

Objective: To determine whether, in nonurban areas, direct transport to a thrombectomy-capable center is beneficial compared with transport to the closest local stroke center.

Design, setting, and participants: Multicenter, population-based, cluster-randomized trial including 1401 patients with suspected acute large-vessel occlusion stroke attended by emergency medical services in areas where the closest local stroke center was not capable of performing thrombectomy in Catalonia, Spain, between March 2017 and June 2020. The date of final follow-up was September 2020.

Interventions: Transportation to a thrombectomy-capable center (n = 688) or the closest local stroke center (n = 713).

Main outcomes and measures: The primary outcome was disability at 90 days based on the modified Rankin Scale (mRS; scores range from 0 [no symptoms] to 6 [death]) in the target population of patients with ischemic stroke. There were 11 secondary outcomes, including rate of intravenous tissue plasminogen activator administration and thrombectomy in the target population and 90-day mortality in the safety population of all randomized patients.

Results: Enrollment was halted for futility following a second interim analysis. The 1401 enrolled patients were included in the safety analysis, of whom 1369 (98%) consented to participate and were included in the as-randomized analysis (56% men; median age, 75 [IQR, 65-83] years; median National Institutes of Health Stroke Scale score, 17 [IQR, 11-21]); 949 (69%) comprised the target ischemic stroke population included in the primary analysis. For the primary outcome in the target population, median mRS score was 3 (IQR, 2-5) vs 3 (IQR, 2-5) (adjusted common odds ratio [OR], 1.03; 95% CI, 0.82-1.29). Of 11 reported secondary outcomes, 8 showed no significant difference. Compared with patients first transported to local stroke centers, patients directly transported to thrombectomy-capable centers had significantly lower odds of receiving intravenous tissue plasminogen activator (in the target population, 229/482 [47.5%] vs 282/467 [60.4%]; OR, 0.59; 95% CI, 0.45-0.76) and significantly higher odds of receiving thrombectomy (in the target population, 235/482 [48.8%] vs 184/467 [39.4%]; OR, 1.46; 95% CI, 1.13-1.89). Mortality at 90 days in the safety population was not significantly different between groups (188/688 [27.3%] vs 194/713 [27.2%]; adjusted hazard ratio, 0.97; 95% CI, 0.79-1.18).

Conclusions and relevance: In nonurban areas in Catalonia, Spain, there was no significant difference in 90-day neurological outcomes between transportation to a local stroke center vs a thrombectomy-capable referral center in patients with suspected large-vessel occlusion stroke. These findings require replication in other settings.

Trial registration: ClinicalTrials.gov Identifier: NCT02795962.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Pérez de la Ossa reported receiving grants from the Spanish Ministry of Health (cofinanced by Fondo Europeo de Desarrollo Regional) and the PERIS program of the Catalan Health Government and receiving grants and personal fees from Medtronic and the Boehringer Angels Initiative. Dr Jovin reported receiving travel-related expense reimbursement from Fundacio Ictus during the conduct of the study; serving on the steering committee/data and safety monitoring board for Cerenovus and the steering committee for Contego Medical; receiving grants from Stryker Neurovascular and Medtronic; and holding stock in and/or being an advisor for Anaconda Biomed, Blockade Medical, Galaxy, Route 92, Corindus, FreeOx Biotech, Viz.ai, and Methinks. Dr San Román Manzanera reported being a proctor for Stryker and Medtronic. Ms Salvat-Plana reported receiving a grant from CIBER Epidemiología y Salud Pública (CIBERESP). Dr Molina reported receiving honoraria for participation in clinical trials, contribution to advisory boards, or oral presentations from AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Bristol Myers Squibb, Covidien, Cerevast, and Brainsgate. Dr Davalos reported receiving consultancy and advisory board fees from Medtronic Neurovascular and an unrestricted grant for the REVASCAT trial from Medtronic (paid to his institution). Dr Ribo reported being an advisor and shareholder in Anaconda Biomed and Methinks and receiving grants and personal fees from Medtronic and personal fees from Stryker, Cerenovus, Philips, iSchemaView, and Apta Targets. No other disclosures were reported.

Figures

Figure 1.. Participant Flow Through the RACECAT Trial

EMS indicates emergency medical services; mRS, modified Rankin Scale. aThe Rapid Arterial Occlusion Evaluation (RACE) Scale ranges from 0 to 9 (lower to higher stroke severity, respectively; see eFigure 1 in Supplement 1). A score greater than 4 was the cut point to identify patients with a large-vessel occlusion. EMS personnel contacted a neurologist if the RACE Scale score was greater than 3 to provide high sensitivity in identifying trial candidates, although a score greater than 4 was considered the inclusion criterion. bRandomization into 1 of the 2 intervention groups was carried out in real time by a smartphone-based app in a 1:1 ratio according to a temporal cluster design. Written informed consent was obtained after patients arrived at the hospital. cThe target population, in which the primary hypothesis was tested, included patients with confirmed diagnosis at discharge of ischemic stroke or transient ischemic attack/averted stroke.

Figure 2.. Distribution of Global Disability at 90 Days in Prespecified Populations

Distribution of modified Rankin Scale (mRS) scores at 90 days in prespecified subgroups of patients initially transported to a thrombectomy-capable stroke center vs a local stroke center who were evaluated by telephone interview with blinded investigators. See Figure 3 footnote b for description of mRS scores. Scores of 5 and 6 were combined for the analysis. Effects are reported below as common odds ratios (ORs) for better outcome, adjusted by stratifying factors, age, and Rapid Arterial Occlusion Evaluation (RACE) Scale score, for each specific population. The local stroke center group was the reference category. Data in the shaded boxes are percentage of patients. Panel A, Primary outcome in the target population, which includes patients with ischemic stroke or transient ischemic attack (TIA)/averted stroke (adjusted common OR, 1.03; 95% CI, 0.812-1.29). Panels B-D show secondary planned analyses. Panel B, Population as randomized (adjusted common OR, 1.05; 95% CI, 0.86-1.27). Panel C, patients with intracranial hemorrhage (adjusted common OR, 0.72; 95% CI, 0.44-1.18). Panel D, patients with stroke mimic (adjusted common OR, 0.90; 95% CI, 0.44-1.85). aFinal diagnoses for patients with stroke mimic included epileptic seizure (n = 39), functional disorder (n = 25), delirium (n = 9), subdural hemorrhage (n = 8), migraine (n = 7), intracranial tumor (n = 5), and cardiovascular syncope (n = 5). Diagnosis was not reported in 8 patients (7%).

Figure 3.. Odds Ratios of a 1-Point Reduction in the Modified Rankin Scale (mRS) Score at 90 Days in Prespecified Subgroups

Effect sizes for the primary outcome of reduced disability (common odds ratio for 1-point reduction in mRS score) at 90 days, analyzed by ordinal logistic regression and adjusted for stratification factors, age, and Rapid Arterial Occlusion Evaluation (RACE) Scale score in prespecified subgroups by age, sex, baseline functional status, tissue plasminogen activator (tPA) treatment eligibility, and RACE Scale score during emergency medical services (EMS) evaluation. aPatients were considered eligible for intravenous tPA administration at the time of randomization after evaluation by EMS personnel if the estimated travel time to the nearest stroke center was less than 4 hours and they received no anticoagulation treatment. bScores on the mRS range from 0 to 6, with 0 indicating no symptoms; 1, no clinically significant disability; 2, slight disability (able to handle own affairs without assistance but unable to carry out all previous activities); 3, moderate disability requiring some help but able to walk unassisted; 4, moderately severe disability (unable to attend to bodily needs and unable to walk); 5, severe disability (requiring constant nursing care and attention); and 6, death. Scores of 5 and 6 were combined for the analysis. cRACE Scale scores range from 0 to 9 (lower to higher stroke severity, respectively). A score greater than 4 was the cut point to identify patients with a large-vessel occlusion and was considered the inclusion criterion.