Thrombolysis With Recombinant Non-immunogenic Staphylokinase vs Surgery in Patients With Acute Limb Ischemia FORAT Trial

Study Overview
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Brief Summary
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Objective: to evaluate the efficacy and safety of intra-arterial intrathrombus administration of the recombinant non-immunogenic staphylokinase (Fortelyzin®) in patients with acute limb ischemia (ALI) vs surgery.

Detailed Description
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Fortelyzin® (the active substance Forteplase) is a recombinant non-immunogenic staphylokinase with high fibrinselective thrombolytic activity. In a multicentre, randomised clinical trial in patients with ST-segment elevation myocardial infarction (FRIDOM), non-immunogenic staphylokinase was administered as a single intravenous bolus of 15 mg in all patients, regardless of bodyweight, and showed similar high reperfusion patency and fewer minor bleeding events compared with tenecteplase, as well as the absence of neutralising IgGs. Results of the multicentre, randomised clinical trial in patients with an acute ischaemic stroke (FRIDA) suggested that the non-immunogenic staphylokinase administrated as a single intravenous bolus of 10 mg in all patients within the 4-5 h after the onset of symptoms is non-inferior to alteplase. Mortality, symptomatic intracranial haemorrhage, and serious adverse events did not differ between treatment groups. Mortality in the ALI continues to be high. According to the Guidelines on the management of patients with ALI, intravenous systemic thrombolysis is ineffective in patients with this condition. In contrast, catheter-directed thrombolysis based on the principle that activation of fibrin-bound plasminogen to the active enzyme plasmin is the most effective approach of lysing pathologic thrombi in the lower extremities of I-II b degree of ALI (Evidence level I-A). So the main objective of this study is to evaluate the efficacy and safety of intra-arterial intrathrombus administration of the recombinant non-immunogenic staphylokinase (Fortelyzin®) in patients with ALI vs surgery.

Official Title
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Multicenter, Open-label, Randomized Clinical Trial of Efficacy and Safety of the Thrombolysis With Recombinant Non-immunogenic Staphylokinase (Fortelyzin®) in Patients With ALI vs Surgery

Conditions
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Acute Limb Ischemia

Intervention / Treatment
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* Drug: Recombinant non-immunogenic staphylokinase (Fortelyzin®)
* Procedure: surgical methods of treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women aged 18 and older; Diagnosis of I-II b degree of ALI; Patient consent to use reliable contraceptive methods throughout the study and for 3 weeks after: women who have a negative pregnancy test and use the following contraceptives: intrauterine devices, oral contraceptives, contraceptive patch, prolonged injectable contraceptives, double barrier method of contraception. Women who are not fertile can also take part in the study (documented conditions: hysterectomy, tubal ligation, infertility, menopause for more than 1 year); men using barrier contraception. The study may also involve men who are not fertile (documented conditions: vasectomy, infertility); Availability of signed and dated informed consent of the patient to participate in the study. Exclusion Criteria: Extensive bleeding at present; Intracranial (including subarachnoid) hemorrhage at present; Recent gastrointestinal bleeding (within 10 days); Major surgery or major trauma within the previous 3 months, recent traumatic brain injury; Systolic blood pressure above 180 mm Hg or diastolic blood pressure above 110 mm Hg or the need for intravenous drugs to lower blood pressure to these limits; Pregnancy, lactation; Known hypersensitivity to Fortelyzin®; Platelet count less than 100,000/µL

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: At clinical centers, patients will be randomly distributed by the envelope method into two groups for assignation Fortelyzin® or surgical methods of treatment.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Recombinant non-immunogenic staphylokinase<br>lyophilisate for preparation a solution, 5 mg (745,000 IU) in 20 ml over 1 minute through a perforated multihole catheter intrathrombally. 30 minutes after this injection, infusion of recombinant non-immunogenic staphylokinase will be continued at a dose of 1 mg/hour, maximum 10 mg (50 ml) for 10 hours through a perforated multihole catheter intrathrombally. | Drug: Recombinant non-immunogenic staphylokinase (Fortelyzin®)<br>* lyophilisate for preparation a solution<br>* Other names: Fortelyzin®;|
| Experimental: Surgical methods of treatment<br>endovascular intervention, open surgery and/or bypass surgery in accordance with the current National Guidelines | Procedure: surgical methods of treatment<br>* Endovascular intervention, open surgery and/or bypass surgery in accordance with the current National Guidelines<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients without amputations | Outcome Measure is evaluated in terms of the number of patients without amputations | 30 days post randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acute limb ischemia, thrombolysis, thrombosis