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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Recombinant non-immunogenic staphylokinase (Fortelyzin®)
  lyophilisate for preparation a solution
• Процедура surgical methods of treatment
  Endovascular intervention, open surgery and/or bypass surgery in accordance with the current National Guidelines

Первичные конечные точки

• Number of patients without amputations [Срок оценки: 30 days post randomization]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Россия · 8 центров

• Kursk city emergency hospital — Kursk
• Sergiyev Posad Regional Clinical Hospital — Sergiyev Posad
• Kaliningrad Regional Clinical Hospital — Kaliningrad
• Kazan City Hospital No. 7 — Kazan'
• S.S. Yudin City clinical hospital — Moscow
• S.P. Botkin Moscow Multidisciplinary Scientific and Clinical Center — Moscow
• Ufa Emergency City Hospital — Ufa
• Volgograd City Clinical Hospital of Emergency #25 — Volgograd

Публикации

• Gusev EI, Martynov MY, Nikonov AA, Shamalov NA, Semenov MP, Gerasimets EA, Yarovaya EB, Semenov AM, Archakov AI, Markin SS; FRIDA Study Group. 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. 2021 Sep;20(9):721 PMID 34418399
• Zatevakhin II, Chupin AV, Karpenko AA, Savello AV, Zolkin VN, Yarovaya EB, Kutsenko VA, Ivanov SV, Semenov MP, Semenov AM, Markin SS. [Intraarterial intrathrombus thrombolysis with non-immunogenic staphylokinase vs surgery in patients with acute limb ischemia: protocol of a multicenter, open-label, randomized clinical trial FORAT]. Angiol Sosud Khir. 2025 Jun 2;31(2):33-41. doi: 10.33029/1027-6661 PMID 41805599

Идентификаторы

NCT: NCT05372718 · FORAT

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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