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

Abstract

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, multicenter, 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, allows 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.

• Authors: E I Gusev, M Yu Martynov, N A Shamalov, E B Yarovaya, M P Semenov, A M Semenov, A A Orlovsky, V A Kutsenko, A A Nikonov, S B Aksentiev, D S Yunevich, A M Alasheev, O V Androfagina, V V Bobkov, K V Choroshavina, V I Gorbachev, I V Korobeynikov, I V Greshnova, A V Dobrovolskiy, U A Elemanov, N V Zhukovskaya, S A Zakharov, A N Chirkov, L L Korsunskaya, V N Nesterova, A A Nikonova, A A Nizov, A I Girivenko, E A Ponomarev, D V Popov, S A Pribylov, A S Semikhin, L V Timchenko, O N Jadan, S A Fedyanin, Zh Yu Chefranova, Yu A Lykov, S E Chuprina, A A Vorobev, A I Archakov, S S Markin
• Journal: Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova (Zh Nevrol Psikhiatr Im S S Korsakova) Vol. 122 Issue 7 Pg. 56-65 ( 2022) ISSN: 1997-7298 [Print] Russia (Federation)
• Vernacular Title: Neimmunogennaya stafilokinaza — novyi tromboliticheskii preparat v lechenii ishemicheskogo insul'ta (rezul'taty issledovaniya FRIDA).
• PMID: 35904293 (Publication Type: Equivalence Trial, Journal Article, Multicenter Study)

Chemical References

• Fibrinolytic Agents
• Metalloendopeptidases
• auR protein, Staphylococcus aureus

Topics

• Body Weight
• Brain Ischemia (complications, drug therapy)
• Fibrinolytic Agents (therapeutic use)
• Humans
• Intracranial Hemorrhages (chemically induced, complications)
• Ischemic Stroke
• Metalloendopeptidases (therapeutic use)
• Stroke (drug therapy, etiology)
• Thrombolytic Therapy
• Treatment Outcome