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

Phase 3

Recruiting

• Conditions: Acute Limb Ischemia
• Interventions: Drug: Recombinant non-immunogenic staphylokinase (Fortelyzin®); Procedure: surgical methods of treatment

• Registration Number: NCT05372718
• Lead Sponsor: Supergene, LLC

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2022-04-28
• Study First Submitted QC: 2022-05-12
• Study First Posted: 2022-05-13
• Study Start: 2022-12-26
• Status Verified: 2023-04
• Last Update Submitted: 2023-04-18
• Last Update Posted: 2023-04-19
• Primary Completion: 2025-05-01
• Study Completion: 2025-07-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 170

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Recombinant non-immunogenic staphylokinase	Recombinant non-immunogenic staphylokinase (Fortelyzin®)	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.
Surgical methods of treatment	surgical methods of treatment	endovascular intervention, open surgery and/or bypass surgery in accordance with the current National Guidelines

Primary Outcome Measures

Name	Time	Method
Number of patients without amputations	30 days post randomization	Outcome Measure is evaluated in terms of the number of patients without amputations

Trial Locations

Locations (7)

Sergiyev Posad Regional Clinical Hospital; 🇷🇺 Sergiyev Posad, Moscow Region, Russian Federation

Kazan State Medical University; 🇷🇺 Kazan, Republic Of Tatarstan, Russian Federation

S.S. Yudin City clinical hospital; 🇷🇺 Moscow, Russian Federation

Federal Scientific and Clinical Center for Specialized Types of Medical Care and Medical Technologies of the Federal Medical and Biological Agency; 🇷🇺 Moscow, Russian Federation

Rostov State Medical University; 🇷🇺 Rostov-on-Don, Russian Federation

Tver Regional Clinical Hospital; 🇷🇺 Tver, Russian Federation

Volgograd City Clinical Hospital of Emergency #25; 🇷🇺 Volgograd, Russian Federation