Multicenter Open Lable Randomized Comparative Study of Efficacy and Safety of Single Bolus Injection of Recombinant Nonimmunogenic Staphylokinase (Fortelyzin) and Tenecteplase (Metalyse) in STEMI Patients
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Enrollment
- 382
- Locations
- 16
- Primary Endpoint
- The Number of Participants With Reperfusion
Study Overview
Brief Summary
The aim of the study is to determine if single-bolus recombinant nonimmunogenic staphylokinase is effective and save thrombolytic agent in patients presenting ST-segment elevation myocardial infarction in comparison to tenecteplase.
Detailed Description
Experimental Drug Profile. The active substance of Fortelyzin is Forteplase. It's recombinant protein which contains aminoacid sequence of staphylokinase. It is single chain molecula, consists of 138 aminoacids, weight 15.5 kDa. When staphylokinase is added to human plasma containing a fibrin clot, it preferentially reacts with plasmin at the clot surface, forming a plasmin-staphylokinase complex. This complex activates plasminogen trapped in the thrombus. The plasmin-staphylokinase complex and plasmin bound to fibrin are protected from inhibition by alpha2-antiplasmin. Once liberated from the clot (or generated in plasma), however, they are rapidly inhibited by alpha2-antiplasmin. This selectivity of action confines the process of plasminogen activation to the thrombus, preventing excessive plasmin generation, alpha2-antiplasmin depletion, and fibrinogen degradation in plasma. In rabbits anti forteplase antibodies are not produced. It was achieved by replacement of amino acids in immunogenic epitop of molecule staphylokinase. Blood fibrinogen decrease after i.v. injection of Fortelyzin less 10% within first 24 hours. Angiographic data suggests that restoration of coronary blood flow appears in up to 80% of patients with STEMI after i.v. injection of Fortelyzin.
Risk/benifit for trail participants. Expected benefit is normalisation of blood supply of ischemic myocardium. It will allow to preserve normal heart function and avoid heart failure development. The most frequent advers reactions of Fortelyzin are possibilty of bleeding. It is possible occurence of internal bleeding due to peptic ulcer, erosion of the esophagus, haemorrhoid, veins of esophagus and so on. Thorough collection of patients data and following the drug instruction allows to dicrease risk of bleeding. The benefit of using fibrinolytics for patients with STEMI is supposed to be higher then risk of bleeding. The reperfusion arrhythmias may occur so the careful ECG monitiring is required.
Main goals of the study
- to prove an efficacy of the single-bolus intravenous injection of recombinant nonimmunogenic staphylokinase (Fortelyzin) in comparison with single-bolus tenecteplase (Metalyse) in patients with ST-segment elevation myocardial infarction
- to prove a safety and to assess possible adverse events in the single-bolus intravenous injection of recombinant nonimmunogenic staphylokinase (Fortelyzin) in comparison with single-bolus tenecteplase (Metalyse) in patients with ST-segment elevation myocardial infarction
Study Design. All eligible patients will be randomized in two equal groups for administration recombinant nonimmunogenic staphylokinase (Fortelyzin) or tenecteplase (Metalyse) by using "envelope method" of randomization. It is an open-lable study. Each of agents will be administered no longer then 12 hours from symptoms onset. Experimental and comparative agent will be administered as prescribed in its instructions.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •both gender patients over 18 years
- •12-lead ECG indicative of an STEMI (ST-segment elevation in acute myocardial infarction, measured at the J point, should be found in two contiguous leads and be ≥0.25 mV in men below the age of 40 years, ≥0.2 mV in men over the age of 40 years, or ≥0.15 mV in women in leads V2-V3 and/or ≥0.1 mV in other leads (in the absence of left ventricular hypertrophy or left bundle branch block
- •the possibility of fibrinolysis within 12 hour of symptom onset
- •inability of primary PCI within 60 min of first medical contact (FMC)
- •informed consent received
Exclusion Criteria
- •expected performance of PCI less 60 min from FMC
- •left bundle branch block or ventricular pacing
- •cases of sinus bradycardia associated with hypotension, AV block II (Mobitz 2) or AV block III with bradycardia that causes hypotension or heart failure
- •active bleeding or known bleeding disorders/diathesis
- •uncontrolled hypertension, defined us single blood pressure measurement ≥180/110 mm Hg prior to randomization
- •internal bleeding within the past 2 weeks
- •conditions with increased risk of bleeding (peptic ulceration)
- •prolonged or traumatic resuscitation within the past 2 weeks
- •any known history of hemorrhagic stroke, or transitory ischemic attack
- •ischemic stroke within the past 3 month
- •puncture of unpressable vessels
- •aortic aneurism
- •intracranial neoplasm
- •any head trauma within past 2 weeks
- •intracranial vessel malformation
- •recent administration of anticoagulant within the past month
- •INR >1.3
- •sensibilisation to staphylokinase
- •contra-indications to acetylsalicilic acid, clopidogrel, enoxaparin
- •any conditions with unfavorable prognosis
- •in case of surgical treatment required within 30 days after randomization
- •in case of unhallowed medications required
- •pregnancy, lactation
- •inability to follow the protocol
Arms & Interventions
Recombinant staphylokinase
Lyophilizate for solution making for intravenous injection, 5 mg (745000 ME). 15 mg of drug reconstituted in 15 ml of 0.9% solution of NaCl given as single i.v. bolus over 5 - 10 seconds
Intervention: Recombinant staphylokinase (Drug)
Tenecteplase
50 mg of drug reconstituted in 10 ml sterile water for injection given as single weight-adjusted i.v. bolus over 5 - 10 seconds Weight (kg) Dose (mg) Dose (ml)
- 55 to <60 30 mg 6 ml
- 60 to <70 35 mg 7 ml
- 70 to <80 40 mg 8 ml
- 80 to <90 45 mg 9 ml
- 90 50 mg 10 ml
Intervention: Tenecteplase (Drug)
Outcomes
Primary Outcomes
The Number of Participants With Reperfusion
Time Frame: 90 min after fibrinolysis
The number of participants with reperfusion by TIMI (Thrombolysis in Myocardial Infarction) 2-3 assessed by coronary arteriography, where grade 0 - no perfusion, grade 1 - penetration without perfusion, grade 2 - partial perfusion, grade 3 - complete perfusion.
Secondary Outcomes
- Composite Endpoint(within 30 days after fibrinolysis)
- Cardiovascular Death(within 30 days after fibrinolysis)
- Repeated Target Vessel Revascularization(within 30 days after fibrinolysis)
- Rehospitalization Due to Cardiovascular Reasons(within 30 days after fibrinolysis)
- Development of Heart Failure(within 30 days after fibrinolysis)
- Overall Bleeding(within 30 gays after fibrinolysis)
- Intracranial Haemorrhages(within 30 days after fibrinolysis)