The goal of this clinical study is to evaluate the efficacy and safety of Longidaza®,lyophilisate for preparation of solution for injection, at a dose of 3000 IU compared toplacebo in the treatment of adult patients with residual changes in the lungs afterCOVID-19 infection
The main objective of the clinical study was to prove the superiority of the efficacy of
the drug Longidaza® over placebo when used in adult patients with residual changes in the
lungs after COVID-19 infection based on the dynamics of respiratory function
Drug: Longidaza®
dose 3000 IU intramuscularly once every 5 days, 15 injections
Other Name: Bovhyaluronidase azoximer
Drug: Placebo
intramuscularly once every 5 days, 15 injections
Inclusion Criteria:
1. Male and female patients aged 18 to 80 years, who signed an informed consent form.
2. The condition after infection with COVID-19, documented in the period from 1 to 12
months before screening (ICD-10: U07.1, U07.2), including accompanied by
hospitalization of the patient.
3. The presence of a negative result of the polymerase chain reaction test (PCR) during
screening and an express test for the SARS-CoV-2 antigen at visit 2.
4. The presence of respiratory symptoms (at least dyspnea), while the severity of
dyspnea on the mMRC during screening is ≥ 1 point.
5. The value of hemoglobin oxygen saturation: SpO2 < 95% at rest at the screening;
and/or desaturation (decrease of SpO2 by ≥ 4% in the 6MWT relative to the value at
rest) at the screening.
6. The presence of residual changes in the lung parenchyma characteristic of previous
COVID-19 infection, > 10% of the area, according to CT at the screening
7. Respiratory dysfunction of the restrictive type at the screening: FVC < 80%, FVC 1 /
FVC > 70%.
Exclusion Criteria:
1. A history of chronic respiratory diseases (interstitial lung disease, chronic
obstructive pulmonary disease, bronchial asthma, bronchiectasis, lung cancer).
2. Clinical signs or anamnesis data on the presence of diseases that, according to the
researcher, can lead to restrictive changes in respiratory function (pronounced
kyphoscoliosis, pleural effusion, neuromuscular diseases), pathological obesity,
etc.
3. Clinical signs or anamnesis data on the presence of unstable angina pectoris, stable
angina pectoris of high functional class, clinically significant cardiac
arrhythmias, chronic heart failure, pulmonary hypertension, suffered pulmonary
embolism or acute myocardial infarction in within 6 months prior to screening.
4. Dyspnea of any other etiology: thyrotoxicosis, anemia (hemoglobin less than 100
g/l), pathological obesity (BMI ≥ 40 kg/m2), metabolic acidosis, neuromuscular
diseases according to anamnesis or screening examination.
5. The presence of an acute infectious process of any etiology and localization.
6. Allergic reactions to the administration of azoximer bovhyaluronidase or an
auxiliary component of the studied drug (mannitol) in the anamnesis.
7. Clinical signs of pulmonary hemorrhage and/or hemoptysis during examination and in
the anamnesis.
8. Confirmed eye injuries with vitreous hemorrhage during the last 6 months according
to the medical history.
9. Malignant neoplasms of any localization in the anamnesis, with the exception of in
situ carcinoma, which required only surgical treatment.
10. Renal failure.
11. Taking drugs of prohibited therapy since the start of screening in this study.
12. Serological test positive for HIV infection, viral hepatitis B and C.
13. Pregnancy or breastfeeding.
14. Participation in clinical trials of an experimental drug within 30 days prior to
screening for participation in the current study.
15. Any other medical or social conditions that, in the opinion of the research
physician, do not allow the patient to participate in this study.
State Autonomous Healthcare Institution of the Sverdlovsk region "Aramil City Hospital"
Aramil 1511466, Russia
Private healthcare institution "Clinical Hospital "RZD-Medicine" of the city of Chelyabinsk"
Chelyabinsk 1508291, Russia
State Budgetary Healthcare Institution "Regional Clinical Hospital No. 3"
Chelyabinsk 1508291, Russia
Alliance Biomedical-Ural Group LLC
Izhevsk 554840, Russia
Federal State Budgetary Educational Institution of Higher Education "Kazan State Medical University" of the Ministry of Health of the Russian Federation. The State Autonomous healthcare institution "Hospital for War Veterans of Kazan"
Kazan' 551487, Russia
Federal State Budgetary Educational Institution of Higher Education "Kazan State Medical University" of the Ministry of Health of the Russian Federation
Kazan' 551487, Russia
State Autonomous Healthcare Institution "Kuzbass Clinical Hospital of Emergency Medical Care named after M.A. Podgorbunsky"
Kemerovo 1503901, Russia
Medical Center Rhevma-Med LLC
Kemerovo 1503901, Russia
Federal State Budgetary Educational Institution of Higher Education "Kirov State Medical University" of the Ministry of Health of the Russian Federation
Kirov 548408, Russia
Federal State Budgetary Institution "National Medical Research Center for Therapy and Preventive Medicine" of the Ministry of Health of the Russian Federation
Moscow 524901, Russia
Federal Budgetary Institution of Science "Central Research Institute of Epidemiology" of the Federal Service for Supervision of Consumer Rights Protection and Human Well-being
Moscow 524901, Russia
Unimed-S Zao
Moscow 524901, Russia
I.M. Sechenov First Moscow State Medical University
Moscow 524901, Russia
ErSi Medical LLC
Novosibirsk 1496747, Russia
Professorial Clinic LLC
Perm 511196, Russia
Energia Zdoroviya LLC
Saint Petersburg 498817, Russia
Medical Center Reavita Med SPb LLC
Saint Petersburg 498817, Russia
Reavita Med SPb Medical Center LLC
Saint Petersburg 498817, Russia
St. Petersburg State Budgetary Healthcare Institution "City Consultative and Diagnostic Center No. 1".
Saint Petersburg 498817, Russia
Eco-Safety Research Center LLC
Saint Petersburg 498817, Russia
Federal State Budgetary Institution "Consultative and Diagnostic Center with Polyclinic" of the Office of the President of the Russian Federation
Saint Petersburg 498817, Russia
St. Petersburg State Budgetary Healthcare Institution "Consultative and Diagnostic Center No.85"
Saint Petersburg 498817, Russia
Astarta LLC
Saint Petersburg 498817, Russia
Federal State Budgetary Educational Institution of Higher Education "Saratov State Medical University named after V.I. Razumovsky" of the Ministry of Health of the Russian Federation
Saratov 498677, Russia
Regional State budgetary healthcare institution "Clinical Hospital No. 1"
Smolensk 491687, Russia
Federal State Budgetary Educational Institution of Higher Education "Siberian State Medical University" of the Ministry of Health of the Russian Federation
Tomsk 1489425, Russia
Budgetary healthcare institution of the Voronezh region "Voronezh Regional Clinical Hospital No. 1"
Voronezh 472045, Russia
Medical Center for Diagnosis and Prevention plus LLC
Yaroslavl 468902, Russia
The State Autonomous Healthcare Institution of the Yaroslavl region "Clinical Hospital No. 9"
Yaroslavl 468902, Russia
Ural research Institute of Phthisiopulmonology
Yekaterinburg 1486209, Russia
Sergey Avdeev, DM, Principal Investigator
I.M. Sechenov First Moscow State Medical University