Acute Limb IschemiaPhase 3FORATNCT05372718
Thrombolysis With Recombinant Non-immunogenic Staphylokinase vs Surgery in Patients With Acute Limb Ischemia FORAT Trial
A Phase 3 study testing Recombinant non-immunogenic staphylokinase (Fortelyzin®) and surgical methods of treatment in people with Acute Limb Ischemia, run by Supergene, LLC at 8 sites in Russia.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Limb Ischemia
- What is being tested?
- Recombinant non-immunogenic staphylokinase (Fortelyzin®) and surgical methods of treatment
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 170 participants
- Where
- 8 sitesRussia
- Study dates
- 26 Dec 2022to 30 Sep 2026
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
Russia8 sites
Kaliningrad Regional Clinical Hospital
Kaliningrad, 236016
Kazan City Hospital No. 7
Kazan', 420103
Kursk city emergency hospital
Kursk, Kursl Region, 305035
S.S. Yudin City clinical hospital
Moscow, 115446
S.P. Botkin Moscow Multidisciplinary Scientific and Clinical Center
Moscow, 125284
Sergiyev Posad Regional Clinical Hospital
Sergiyev Posad, Moscow Oblast, 141301
Ufa Emergency City Hospital
Ufa, 450092
Volgograd City Clinical Hospital of Emergency #25
Volgograd, 400138
About this study
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
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.
Read the 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.
- Conditions
- Acute Limb Ischemia
- Being tested
- Recombinant non-immunogenic staphylokinase (Fortelyzin®), surgical methods of treatment
- Keywords
- acute limb ischemia, thrombolysis, thrombosis
- Medical subject headings
- Thrombosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Recombinant non-immunogenic staphylokinase (Fortelyzin®)Drug
Also called Fortelyzin®
lyophilisate for preparation a solution
surgical methods of treatmentProcedure or surgery
Endovascular intervention, open surgery and/or bypass surgery in accordance with the current National Guidelines
| Study group | Role | What they receive |
|---|---|---|
| Recombinant non-immunogenic staphylokinase | Experimental | 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. Receives: Drug: Recombinant non-immunogenic staphylokinase (Fortelyzin®) |
| Surgical methods of treatment | Experimental | endovascular intervention, open surgery and/or bypass surgery in accordance with the current National Guidelines Receives: Procedure: surgical methods of treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients without amputations
Outcome Measure is evaluated in terms of the number of patients without amputations
Measured: 30 days post randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2022
- Study start26 Dec 2022
- Primary completion30 Sep 2026
- Study completion30 Sep 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Acute Limb IschemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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)
- Enrolment
- 170 participants (actual)
Sponsor and investigators
- Lead sponsor
- Supergene, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Igor I. Zatevakhin, MD, PhD, Principal investigator, N.I. Pirogov Russian Medical University, President of the Russian Society of SurgeonsSergey S. Markin, MD, PhD, Study director, Supergene, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05372718
- Sponsor's protocol ID
- FORAT
- Acronym
- FORAT
- Status last verified
- Sep 2026
- First submitted
- 28 Apr 2022
- Last updated
- 5 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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):721-728. doi: 10.1016/S1474-4422(21)00210-6.
PubMed 34418399Zatevakhin 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: 10.33029/1027-6661-2025-31-2-33-41. Russian.
PubMed 41805599
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05372718
- Acronym / sponsor ID
- FORAT / FORAT
- Conditions
- Acute Limb Ischemia
- Keywords
- acute limb ischemia, thrombolysis, thrombosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 170 participants (actual)
- Lead sponsor
- Supergene, LLCIndustry (pharma, biotech, devices)
- Study start
- 26 Dec 2022 (actual)
- Primary completion
- 30 Sep 2026 (actual)
- Study completion
- 30 Sep 2026 (actual)
- First posted
- 13 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Recombinant non-immunogenic staphylokinase | Experimental | Drug: 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 | Experimental | Procedure: surgical methods of treatmentendovascular intervention, open surgery and/or bypass surgery in accordance with the current National Guidelines |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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:
- Availability of signed and dated informed consent of the patient to participate in the study.
Key exclusion criteria (8 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Recombinant non-immunogenic staphylokinase (Fortelyzin®)Also: Fortelyzin®lyophilisate for preparation a solution | Drug | Recombinant non-immunogenic staphylokinase |
| surgical methods of treatmentEndovascular intervention, open surgery and/or bypass surgery in accordance with the current National Guidelines | Procedure or surgery | Surgical methods of treatment |
Primary outcome
Number of patients without amputations
Time frame: 30 days post randomization
Outcome Measure is evaluated in terms of the number of patients without amputations
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2026.
- Results publication: PubMed 34418399Gusev 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):721-728. doi: 10.1016/S1474-4422(21)00210-6.
- Derived from this study: PubMed 41805599Zatevakhin 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: 10.33029/1027-6661-2025-31-2-33-41. Russian.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Igor I. Zatevakhin, MD, PhD principal investigator
N.I. Pirogov Russian Medical University, President of the Russian Society of Surgeons
Sergey S. Markin, MD, PhD study director
Supergene, LLC
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Recombinant non-immunogenic staphylokinase (Fortelyzin®) and surgical methods of treatment in people with Acute Limb Ischemia, run by Supergene, LLC at 8 sites in Russia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of patients without amputations (time frame: 30 days post randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05372718, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2026; AzTrials last refreshed its copy on 7 Nov 2026.