The observational study will be carried out in two stages. At the first stage, the efficacy and safety of Aprotinin intravenous infusion as add-on therapy to the standard of care will be studied. At the second stage, two groups will be included: the first group will be the inhaled Aprotinin add-on therapy, the second group will be intravenous Aprotinin in combination with Favipiravir.
Primary objective of the study is to evaluate the efficacy of Aprotinin as add-on therapy in patients hospitalized with COVID-19 using the following parameters: * The time to elimination of SARS-CoV-2 virus until Day 10; * The time to C-reactive protein (CRP) normalization until Day 10; * The time to D-dimer normalization until Day 10. Secondary objectives are to evaluate the following parameters of efficacy and safety of Aprotinin add-on therapy in patients hospitalized with COVID-19: * The time to body temperature normalization (\<37oC); * Changes from baseline of the laboratory parameters during 14 days: hematology, CRP, coagulogram; * Changes of lung injury on CT scan on Day 7 and Day 14 from baseline; * Frequency of clinical status improvement by 2 scores in accordance with the WHO Ordinal scale of clinical improvement (WHO-OSCI) or discharge from the hospital before Day 14; * Frequency of transfer to the Intensive Care Unit (ICU), frequency of the non-invasive ventilation, frequency of the invasive ventilation and mortality rate; * Frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs) of various severity according to subjective complains, physical examination, vital signs, laboratory tests and ECG.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Intravenous or inhalation
Regional State Budgetary Healthcare Institution "Clinical Hospital №1"
Smolensk, Russia
Time to elimination of SARS-CoV-2 virus
Time to two negative PCR tests with at least 24 hours interval \[days\]
Time frame: 10 days
Time to CRP normalization
Time to CRP \<10 mg/L \[days\]
Time frame: 10 days
Time to D-dimer normalization
Time to D-dimer \<243 ng/mL \[days\]
Time frame: 10 days
Time to body temperature normalization
Time to body temperature \<37oC \[days\]
Time frame: 14 days
Change in absolute neutrophil count (ANC)
Change of ANC \[cells/L\]
Time frame: Baseline to Day 14
Change in white blood cells (WBC)
Change of WBC \[cells/L\]
Time frame: Baseline to Day 14
Change of CRP
Change of CRP \[mg/L\]
Time frame: Baseline to Day 14
Change of D-dimer
Change of D-dimer \[ng/mL\]
Time frame: Baseline to Day 14
Change in fibrinogen
Change of fibrinogen \[g/L\]
Time frame: Baseline to Day 14
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Change of Quick's value
Change of Quick's value \[%\]
Time frame: Baseline to Day 14
Change of international normalized ratio (INR)
Change of INR \[score\]
Time frame: Baseline to Day 14
Changes of lung injury on CT scan
Improvement, no change or worsening of the lung injury on CT scan \[proportion of patients\]
Time frame: Baseline to Day 14
Frequency of clinical status improvement by 2 scores in accordance with the WHO-OSCI or discharge from the hospital
Frequency of clinical status improvement by 2 scores in accordance with the WHO-OSCI or discharge from the hospital \[proportion of patients\]
Time frame: 14 days
Frequency of deterioration of the patients' status
Frequency of transfer to the ICU, non-invasive ventilation, invasive ventilation and mortality rate \[proportion of patients\]
Time frame: 14 days
Frequency of AEs and SAEs
Frequency of AEs and SAEs of various severity according to subjective complains, physical examination, vital signs, laboratory tests and ECG \[% of patients\]
Time frame: 14 days