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

Acute Limb Ischemia Clinical Trial

— FORAT  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05372718
• Other study ID #: FORAT
• Status: Recruiting
• Phase: Phase 3
• Start date: December 26, 2022
• Est. completion date: July 1, 2025

Study information

• Verified date: April 2023
• Source: Supergene, LLC
• Contact: Sergey S. Markin, MD, PhD
• Phone: (906) 796-89-06
• Email: amsemenof[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 170
• Est. completion date: July 1, 2025
• Est. primary completion date: May 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Limb Ischemia
• Ischemia

Intervention

Drug:
• Recombinant non-immunogenic staphylokinase (Fortelyzin®)
lyophilisate for preparation a solution

Procedure:
• surgical methods of treatment
Endovascular intervention, open surgery and/or bypass surgery in accordance with the current National Guidelines

Locations

Country	Name	City	State
Russian Federation	Kazan State Medical University	Kazan	Republic Of Tatarstan
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	S.S. Yudin City clinical hospital	Moscow
Russian Federation	Rostov State Medical University	Rostov-on-Don
Russian Federation	Sergiyev Posad Regional Clinical Hospital	Sergiyev Posad	Moscow Region
Russian Federation	Tver Regional Clinical Hospital	Tver
Russian Federation	Volgograd City Clinical Hospital of Emergency #25	Volgograd

Sponsors (1)

Lead Sponsor	Collaborator
Supergene, LLC

Country where clinical trial is conducted

Russian Federation, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Safety endpoint - Death from all causes	The safety is evaluated in terms of the number of deaths from all causes	30 days post randomization
Other	Safety endpoint - hemorrhagic stroke	The safety is evaluated in terms of the number of hemorrhagic stroke	30 days post randomization
Other	Safety endpoint - BARC type 3 and 5 bleeding	The safety is evaluated in terms of the number of BARC type 3 and 5 bleeding	30 days post randomization
Other	Safety endpoint - Number and severity of serious adverse events (SAEs) and AEs in organs and systems	The safety is evaluated in terms of the number and severity of SAEs and AEs in organs and systems	30 days post randomization
Primary	Number of patients without amputations	Outcome Measure is evaluated in terms of the number of patients without amputations	30 days post randomization