A Multicenter, Double-blind, Randomized, Placebo-controlled Study of the Efficacy and Safety of the Recombinant Non-immunogenic Staphylokinase in Patients With Acute Ischemic Stroke Within 4.5-24 Hours of Symptom Onset (FRIDA-CT)
Overview
- Phase
- Phase 3
- Status
- Not yet recruiting
- Sponsor
- Supergene, LLC
- Enrollment
- 990
- Locations
- 15
- Primary Endpoint
- Good functional outcome
Overview
Brief Summary
Multicenter, double-blind, randomized, placebo-controlled phase III clinical trial. At the clinical sites, patients with acute ischemic stroke within 4.5-24 hours of symptom onset will be randomized to receive a single bolus injection of the recombinant non-immunogenic staphylokinase (Fortelyzin®, LLC "SuperGene", Russia) or placebo.
Detailed Description
The current guidelines recommended intravenous thrombolysis as the first-line treatment for acute large vessel occlusion of anterior circulation stroke within 4.5 hours of stroke onset. However, a majority of patients arrive in the hospital outside the 4.5-hour time window, who could not receive intravenous thrombolysis.
In 2020, the non-immunogenic staphylokinase was registered in Russia for the acute ischemic stroke treatment within 4,5 h after the onset of symptoms. In the FRIDA randomized clinical trial the non-immunogenic staphylokinase was non-inferior to alteplase for patients with acute ischaemic stroke. Mortality, symptomatic intracranial haemorrhage, and serious adverse events did not differ significantly between groups. Non-immunogenic staphylokinase is easy to administer with a rapid single bolus of 10 mg regardless patients' bodyweight, simplifying clinical use. In 2024, the non-immunogenic staphylokinase has been included in the updated Russian clinical guidelines for the acute ischemic stroke treatment.
A rapid (10 s) single bolus of the non-immunogenic staphylokinase in patients with acute ischemic stroke may provide significant advantages over a one-hour alteplase administration in the more rapid reperfusion in the first 24 hours after thrombolysis and a greater number of good functional outcomes. It can be assumed that the non-immunogenic staphylokinase usage in patients with acute ischemic stroke outside the 4.5-hour therapeutic window will lead to the restoration of collateral blood flow in the penumbra in comparison with standard medical management.
Therefore, FRIDA-CT trial is aimed to investigate the efficacy and safety of the non-immunogenic staphylokinase within the time window of 4.5-24 hours, wake-up stroke or no witness stroke in patients who had an acute ischaemic stroke with salvageable tissue due to large vessel occlusion.
In the multicenter, double-blind, randomized, placebo-controlled phase III clinical trial patients who had an acute ischaemic stroke due to anterior circulation large vessel occlusion (internal carotid artery, middle cerebral artery M1 and M2 segments) within 4.5-24 hours from last known well (including wake-up stroke and no witness stroke) and with salvageable tissue (ischaemic core volume <70 mL, mismatch ratio ≥1.8 and mismatch volume ≥15 mL) based on CT perfusion or MRI perfusion-weighted imaging (PWI) will be included and randomised to the non-immunogenic staphylokinase, 10 mg (single bolus) regardless patient's bodyweight or placebo group. Patients who are intended for direct thrombectomy will be excluded from the trial. Follow-up period will be 90 days.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Men and women aged 18 years and over;
- •Acute ischemic stroke symptom onset between 4.5 to 24 hours prior to enrolment, including wake-up stroke and unwitnessed stroke, onset time refers to "last-seen normal time";
- •Pre-stroke modified Rankin scale (mRS) score≤1;
- •Internal carotid artery, middle cerebral artery M1 or M2 occlusion confirmed by CT/MRI, internal carotid artery, middle cerebral artery M1 or M2 being responsible for signs and symptoms of acute ischemic stroke;
- •Neuroimaging: target mismatch profile on CT or MRI perfusion: ischemic core volume \<70 mL, mismatch ratio≥1.8 and mismatch volume≥15 mL;
- •Alberta Stroke Program Early CT score (ASPECTS) \> 6;
- •Baseline National Institutes of Health Stroke Scale (NIHSS) 6-25 (inclusive);
- •The patient is not planned or cannot undergo thrombectomy or intravenous thrombolysis in accordance with the current version of the Clinical Guidelines;
- •Written informed consent from patients or their legally authorized representatives.
Exclusion Criteria
- •Acute ischemic stroke within 4,5 h after symptom onset;
- •Intended to proceed to endovascular treatment;
- •Known hypersensitivity to the non-immunogenic staphylokinase;
- •Convulsive seizures at the onset of the disease, if there is no certainty that the seizure is a clinical manifestation of acute ischemic stroke;
- •Persistent blood pressure elevation (systolic ≥185 mmHg or diastolic ≥110 mmHg), and the inability to reduce systolic blood pressure below 180 mmHg or diastolic blood pressure below 105 mmHg;
- •Blood glucose \<2.8 or \>22.2 mmol/L (after blood glucose level correction to the specified values, inclusion of the patient in the study is possible);
- •Neuroimaging (CT, MRI) signs of intracranial hemorrhage, brain tumor, arteriovenous malformation, brain abscess, cerebral aneurysm;
- •Subarachnoid hemorrhage;
- •Major bleeding currently or within the past 6 months;
- •Surgery on the brain or spinal cord in the last 2 months;
Arms & Interventions
Non-immunogenic staphylokinase
The non-immunogenic staphylokinase is given as a single intravenous bolus, 10 mg (within 5-10 seconds) immediately upon randomization regardless patient's bodyweight
Intervention: non-immunogenic staphylokinase (Drug)
Placebo
Placebo
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Good functional outcome
Time Frame: 90 days
The number of patients with good functional outcome defined as an mRS score 0-1 at 90 days
Secondary Outcomes
- Ordinal distribution of mRS(90 days)
- Functional independence outcome(90 days)
- NIHSS change from baseline(7-14 days)
- The rate of improvement on reperfusion(24 hours)
- All-cause mortality(90 days)
- Poor functional outcome(90 days)