Objective: to evaluate the efficacy and safety of the non-immunogenic recombinant staphylokinase with its single bolus administration in comparison with placebo in normotensive patients with intermediate high-risk pulmonary embolism (PE)
For patients with massive PE thrombolysis can be life-saving and may reduce a pulmonary obstruction, pulmonary hypertension, and right ventricle dysfunction. Efficacy of the thrombolytic therapy has been proven in patients with high-risk pulmonary embolism accompanied by shock or systemic hypotension. However, the question of whether thrombolytic therapy can improve the clinical outcome of hemodynamically stable patients, i.e. with PE of intermediate high-risk, still remains controversial. In PEITHO trial tenecteplase, administered as a single bolus at a dose of 30-50 mg depending on body weight was compared with a placebo in patients with intermediate high-risk PE with right ventricular dysfunction. Efficacy of tenecteplase was combined with a significant (6.3%) risk of hemorrhagic stroke, which did not allow tenecteplase to be included in the list of recommended thrombolytics for PE treatment. PEITHO-3 trial has now begun, in which patients with intermediate high-risk PE are given a reduced dose of alteplase (0.6 mg/kg infusion with the total dose not exceeding 50 mg) compared with placebo. Staphylokinase is a thrombolytic agent with high biological activity. Amino acid substitutions - including Lys74Ala, Glu75Ala, and Arg77Ala - resulted in a more than 200-times reduction in titres of neutralising antistaphylokinase IgGs in patients with ST-elevation myocardial infarction. In FORPE trial non-immunogenic recombinant staphylokinase was non-inferior as compared with alteplase in patients with high-risk massive PE. The main objectives of this study: to assess the efficacy, safety and possible adverse events of the non-immunogenic recombinant staphylokinase with its single bolus administration in normotensive patients with intermediate high-risk PE in comparison with placebo.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
486
15 mg of drug reconstituted in 15 ml of 0.9% solution of NaCl given as single i.v. bolus over 10-15 seconds
15 mg of placebo reconstituted in 15 ml of 0.9% solution of NaCl given as single i.v. bolus over 10-15 seconds
RZD Medicine hospital
Barnaul, Altayskiy Kray, Russia
Composite of death from any cause or hemodynamic collapse or recurrent PE
The efficacy is evaluated in terms of the number of death from any cause or hemodynamic collapse or recurrent PE
Time frame: within 30 days
Right/left ventricular (RV/LV) end-diastolic diameter ratio
The efficacy is evaluated in terms of the RV/LV end-diastolic diameter ratio according to echocardiography
Time frame: within 24 hours
RV/LV end-diastolic diameter ratio
The efficacy is evaluated in terms of the RV/LV end-diastolic diameter ratio according to computed tomography pulmonary angiography (CTPA)
Time frame: within 24 hours
RV/LV end-diastolic diameter ratio
The efficacy is evaluated in terms of the RV/LV end-diastolic diameter ratio according to echocardiography
Time frame: within 30 days
Right ventricular (RV) end-diastolic volume
The efficacy is evaluated in terms of the RV end-diastolic volume according to CTPA
Time frame: within 24 hours
Qanadli index
The efficacy is evaluated in terms of Qanadli index according to CTPA in points from 0 to 40, where 0 points - absence of thrombotic masses in the pulmonary artery, 40 points - complete occlusion of the pulmonary artery
Time frame: within 24 hours
Systolic pulmonary artery pressure
The efficacy is evaluated in terms of the systolic pulmonary artery pressure according to echocardiography
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V.F. Dolgopolov Vyselki Central District Hospital
Vyselki, Krasnodarskiy Kray, Russia
RECRUITINGAsinovskaya District Hospital
Asino, Tomsk Oblast, Russia
COMPLETEDBelgorod Regional Clinical Hospital of St. Joseph
Belgorod, Russia
RECRUITINGKuzbass Cardiology center
Kemerovo, Russia
RECRUITINGCenter of Neurology and Cardiology
Kirov, Russia
RECRUITINGRegional Clinical Hospital №2
Krasnodar, Russia
RECRUITINGLipetsk City Hospital No. 4 "Lipetsk-Med"
Lipetsk, Russia
RECRUITINGF.I. Inozemtsev City Clinical Hospital
Moscow, Russia
RECRUITINGMoscow Multidisciplinary Clinical Center "Kommunarka"
Moscow, Russia
RECRUITING...and 14 more locations
Time frame: within 24 hours
In hospital death from all causes (assessed up to day 7)
The efficacy is evaluated in terms of the in hospital death from all causes (assessed up to day 7)
Time frame: In hospital period (assessed up to day 7)
Death from all causes
The efficacy is evaluated in terms of the death from all causes
Time frame: within 30 days
Safety endpoint - hemorrhagic stroke
The efficacy is evaluated in terms of the hemorrhagic stroke
Time frame: within 30 days
Safety endpoint - BARC type 3 and 5 bleeding
The efficacy is evaluated in terms of the Bleeding Academic Research Consortium definitions, where type 3a is an overt bleeding with hemoglobin drop of 3 to 5 g/dL and any transfusion with overt bleeding; type 3b is a bleeding requiring surgical intervention or intravenous vasoactive agents; type 3c is an intracranial hemorrhage; type 5 is fatal bleeding.
Time frame: within 30 days
Safety endpoint - number and severity of adverse events (AEs) and serious AEs in organs and systems
The efficacy is evaluated in terms of the number and severity of AEs and serious AEs in organs and systems
Time frame: within 30 days