Importance Clinical trials focusing on new mechanical thrombectomy (MT) technologies have been typically single-arm studies using historical comparison data to determine the safety and efficacy of the novel device. To date, there has not been a contemporaneous prospective, randomized, controlled study comparing standard to newer designed stent-retrievers.

Objective To evaluate the safety and efficacy of the pRESET® (phenox Ltd) compared to the Solitaire™ (Medtronic Corp) thrombectomy devices in the treatment of large vessel occlusion strokes (LVOS).

Methods Multicenter, prospective, randomized, open-label, blinded endpoint, core lab adjudicated, non-inferiority trial that enrolled 340 patients from October 2019 to February 2022 across 19 US & 5 German sites. Patients aged ≥18 years with either anterior or posterior circulation LVOS were included up to 8 hours after symptom onset. Patients were randomly assigned in a 1:1 ratio to either pRESET or Solitaire for the first three device passes. The Primary Endpoint was the proportion of patients achieving a modified Rankin Scale score of 0-2, analyzed by intent to treat with a non-inferiority margin of 0.125 based on the lower bound 95% Confidence Interval. The Primary Safety Endpoint was the proportion of subjects with device- or procedure-related symptomatic intracerebral hemorrhage at 24 (-8/+12) hours as per the SITS-MOST criteria. Secondary Outcome Measures included the rates of (1) Successful Revascularization (defined as expanded Thrombolysis in Cerebrovascular Infarction [eTICI]≥2b50≤3 passes of the assigned device; (2) eTICI ≥2c following the first pass of the assigned device; (3) 90-day mortality and (4) Distribution of 90-day mRS across the entire spectrum of disability (ordinal shift).

Results Among the 340 subjects that were randomized to either pRESET or Solitaire, 322 subjects received treatment with the assigned device. 17 subjects did not proceed to treatment due clot resolution after randomization but before treatment (7 - pRESET, 11- Solitaire). Per Protocol population was 138 for pRESET & 128 for Solitaire. Primary efficacy of mRS≤2 in the Per Protocol population was 59.42% for pRESET & 55.47% for Solitaire (95% CI, pRESET minus Solitaire -6.02% to 13.93%). Primary safety of sICH was 0% in the pRESET arm 0/173 and 1.2% in the Solitaire arm 2/167. Embolization to New Territory (ENT) was 0% in the pRESET arm and 1.2% in the Solitaire arm. First pass success in the Per Protocol population using the eTICI scale ≥2c were not significantly different in both arms (pRESET 46.38% and Solitaire 42.19%, CI 95%, -5.83% to 14.2%).

Conclusions and Relevance PROST is the first randomized clinical trial aiming to compare a novel versus an established stent-retriever technology, establishing a new scientific benchmark for stroke device trials. In all primary & secondary endpoints and analysis, the pre-specified threshold of non-inferiority was met.(ClinicalTrials.gov: NCT03994822)

Disclosures R. Hanel: 1; C; NIH, Interline Endowment, Microvention, Stryker, CNX, Balt. 2; C; Medtronic, Stryker, Cerenovus, Microvention, Phenox, Rapid Medical, Q’Apel. 4; C; InNeuroCo, Cerebrotech, eLum, Endostream, Three Rivers Medical Inc, Scientia, RisT, BlinkTBI, Corindus. J. Klisch: None. M. Möhlenbruch: None. D. Vollherbst: None. C. Ulfert: None. H. Bozorgchami: None. E. A. Samaniego: None. D. S. Liebeskind: None. D. Lobsien: None. D. Pielenz: None. E. Sauvageau: None. A. Aghaebrahim: None. W. M. Clark: None. R. Priest: None. S. Ortega-Gutierrez: None. D. Lopes: None. J. Billingsley: None. D. C. Haussen: None. A. R. Al-Bayati: None. A. H. Siddiqui: None. M. Chen: None. P. Schramm: None. S. Narayanan: None. C. Roth: None. T. Boeckh-Behrens: None. A. E. Hassan: None. J. T. Fifi: None. R. Budzik: None. J. W. Tarpley: None. R. Starke: None. E. Raz: None. R. Nogueira: None.