Clinical trial NCT05372718: Thrombolysis With Recombinant Non-immunogenic Staphylokinase vs Surgery in Patients With Acute Limb Ischemia FORAT Trial
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Acute Limb Ischemia
Keywords: acute limb ischemia
thrombolysis
thrombosis
Lead sponsor: Supergene, LLC
Sponsor class: INDUSTRY
First posted: 2022-05-13
Enrollment: 170
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of patients without amputations
timeFrame: 30 days post randomization
Secondary outcomes:
Other outcomes:
measure: Safety endpoint - Death from all causes
timeFrame: 30 days post randomization
measure: Safety endpoint - hemorrhagic stroke
timeFrame: 30 days post randomization
measure: Safety endpoint - BARC type 3 and 5 bleeding
timeFrame: 30 days post randomization
measure: Safety endpoint - Number and severity of serious adverse events (SAEs) and AEs in organs and systems
timeFrame: 30 days post randomization
Locations:
city: Sergiyev Posad
country: Russian Federation
facility: Sergiyev Posad Regional Clinical Hospital
state: Moscow Region
city: Kazan
country: Russian Federation
facility: Kazan State Medical University
state: Republic Of Tatarstan
city: Moscow
country: Russian Federation
facility: S.S. Yudin City clinical hospital
city: Moscow
country: Russian Federation
facility: Federal Scientific and Clinical Center for Specialized Types of Medical Care and Medical Technologies of the Federal Medical and Biological Agency
city: Rostov-on-Don
country: Russian Federation
facility: Rostov State Medical University
city: Tver
country: Russian Federation
facility: Tver Regional Clinical Hospital
city: Volgograd
country: Russian Federation
facility: Volgograd City Clinical Hospital of Emergency #25
Study officials:
affiliation: N.I. Pirogov Russian Medical University, President of the Russian Society of Surgeons
name: Igor I. Zatevakhin, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Supergene, LLC
name: Sergey S. Markin, MD, PhD
role: STUDY_DIRECTOR
References:
citation: 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.