Nonimmunogenic staphylokinase in the treatment of acute ischemic stroke (FRIDA trial results)

Aim of the study. To investigate the efficacy and safety of non-immunogenic staphylokinase (NS) compared with alteplase (A) in patients with acute ischemic stroke (AIS) within 4.5 h after symptom onset. Material and methods. 336 patients with IS within 4.5 h after symptom onset were included in a randomized, open-label, multi-center, parallel-group, non-inferiority comparative trial of NS vs A (168 patients in each group). NS was administered as an intravenous bolus in a dose of 10 mg, regardless of body weight, over 10 s, A was administered as a bolus infusion in a dose of 0.9 mg/kg, maximum 90 mg over 1 hour. The primary efficacy endpoint was a favorable outcome, defined as a modified Rankin scale (mRS) score of 0—1 on day 90. Safety endpoints included all-cause mortality on day 90, symptomatic intracranial haemorrhage, and other serious adverse events (SAEs). Results. At day 90, 84 (50%) patients reached the primary endpoint (mRS 0-1) in the NS group, 68 (41%) patients — in the A group (p=0.10, OR=1.47, 95% CI=0.93—2.32). The difference between groups NS and A was 9.5% (95% CI= –1.7—20.7) and the lower limit of the 95% CI did not cross the margin of non-inferiority (pnon-inferiority <0.0001). There were no significant differences in the frequency of deaths between the groups: on day 90, 17 (10%) patients in the NS group and 24 (14%) in the A group had died (p=0.32). There was a trend towards significant differences in the frequency of symptomatic intracranial haemorrhage: NS group — 5 (3%) patients, A group — 13 (8%) patients (p=0.087, OR=0.37, 95% CI=0.1—1.13). There were significant differences in the number of patients with SAEs: in the NS group — 22 (13%) patients, in the A group — 37 (22%) patients (p=0.044, OR=0.53, 95% CI=0.28—0.98). Conclusion. The presented results of the FRIDA trial are the first in the world to use a drug based on NS in patients with IS. It has been shown that a single bolus (within 10 s) administration of NS at a standard dose of 10 mg, regardless of body weight, al-lows to conduct fast, effective and safe thrombolytic therapy in patients with IS within 4.5 h after symptom onset. In further clinical tials of NS, it is planned to expand the therapeutic window beyond 4.5 h after symptom onset in patients with IS. © 2022, Media Sphera Publishing Group. All rights reserved.