Nonimmunogenic staphylokinase was found to be noninferior to alteplase in patients with acute ischemic stroke when administered within 4.5 hours of onset of symptoms, according study findings published in The Lancet Neurology.
In this open label, parallel-group, noninferiority trial held at 18 clinical sites in Russia (FRIDA), patients aged ≥18 years with a diagnosis of acute ischemic stroke (N=336) were randomly assigned to receive either non-immunogenic staphylokinase (n=168) or alteplase (n=168) by block randomization, stratified by age and National Institutes of Health Stroke Scale (NIHSS) score.
The primary efficacy endpoint was a modified Rankin scale (mRS) score of 0-1 on day 90 after drug administration, with the secondary efficacy endpoint defined as simultaneous outcomes of mRS score 0-1, NIHSS score 0-1, and Barthel index score of 95 or more on day 90 after drug administration. Safety endpoints were mortality on day 90, intracranial hemorrhage, symptomatic intracranial hemorrhage, and other serious adverse events (SAEs).
In the nonimmunogenic staphylokinase group, 50% of patients (n=84) had an mRS score of 0-1, compared with 41% of patients (n=68) in the alteplase group (odds ratio [OR] 1.47; 95% CI, 0.93-2.32; P =.10). There was a 9.5% difference in the rate of favorable outcomes (‑1.7 to 20.7), and the lower limit of the 95% CI did not cross the margin of noninferiority (P <.0001 for noninferiority). Patients in the nonimmunogenic staphylokinase group were not associated with an increased reduction in mRS score compared with patients in the alteplase group (OR 1.27; 95% CI, 0.85-1.92; P =.24).
The secondary efficacy endpoint was met by 35% of patients in the nonimmunogenic staphylokinase group (n=59) and in 31% of patients in the alteplase group (n=52; OR, 1.21; 95% CI, 0.75-1.95; P =.49). By day 90, 17 deaths had occurred in the nonimmunogenic staphylokinase group and 24 deaths in the alteplase group. Intracranial hemorrhage occurred in 19% of patients in the nonimmunogenic staphylokinase group (n=31) and in 17% of patients in the alteplase group (n=28; P =.77). Symptomatic intracranial hemorrhage occurred in 3% patients in the nonimmunogenic staphylokinase group (n=5) and in 8% patients in the alteplase group (n=13; P =.087). SAEs occurred in 13% of patient in the nonimmunogenic staphylokinase group and in 22% of patients in the alteplase group (n=37; P =.044).
The main limitation of this study was the 16% noninferiority margin when compared with the noninferiority margin in trials of thrombectomy in the treatment of patients with acute ischemic stroke. Dosages of nonimmunogenic staphylokinase and alteplase differed, with the former being administered as one 10 mg dose for all patients, regardless of bodyweight, whereas the latter was administered as weight-dependent doses (0.9 mg/kg), even in patients weighing ≥100 kg.
“To the best of our knowledge, the findings of the FRIDA study are the first to report use of nonimmunogenic staphylokinase in patients with acute ischaemic stroke,” the researchers concluded. “Observational studies of nonimmunogenic staphylokinase must be done to continue to assess the safety and efficacy of the drug within this time window. In future studies of nonimmunogenic staphylokinase, the superiority of nonimmunogenic staphylokinase compared with alteplase should also be investigated.”
Study authors also recommended that future studies that include reperfusion CT or magnetic resonance angiography be done to assess patients beyond the 4.5 hours following onset of symptoms, incorporating thrombectomy if needed.
Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.
Gusev EI, Martynov MY, Nikonov AA, et al. Non-immunogenic recombinant staphylokinase versus alteplase for patients with acute ischaemic stroke 4·5 h after symptom onset in Russia (FRIDA): a randomised, open label, multicentre, parallel-group, non-inferiority trial. Lancet Neurol. Published online September 1, 2021. doi:10.1016/S1474-4422(21)00210-6