Multicenter, prospective, double-blind, placebo-controlled, randomized, parallel-group phase III study. The study is designed for 2 treatment groups: * Group 1 of the investigational drug - Patients receive standard therapy and the investigational drug. * Group 2 of comparison - Patients receive standard therapy and placebo.
Patients with the severe course of COVID-19 infection confirmed by PCR laboratory test will be involved in the study on a voluntary basis. In accordance with regulatory enactments, these patients receive specialized medical care in specialized medical institutions, where the conduct of the study is planned. The study is planned as a double-blind, which will be achieved by using Molixan and placebo (0.9% NaCl solution) in the same packaging with the same labeling, indistinguishable in color and smell. Patients will be randomized in an unpredictable manner using the IWRS system. It is planned to divide patients into 2 parallel groups: 1. Group 1. Standard therapy + Molixan; 2. Group 2. Standard therapy + placebo. The regimen (1 or 2) assigned to each study subject will not be known to either the Investigator or the patient.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
330
The investigational drug in this study is Molixan in the dosage form of 30 mg/ml solution for intravenous and intramuscular injection. Against the background of standard therapy: Molixan® at a dose of 3.0 mg/kg per day is administered once intravenously (stream injection) with 0.9% sodium chloride solution at a volume ratio of 1:1 for 10 days.
Placebo will be used as a comparator drug and will be an analogue of the investigational drug without active substance. Against the background of standard therapy: Placebo at a dose of 3.0 mg/kg per day is administered once intravenously (stream injection) with 0.9% sodium chloride solution at a volume ratio of 1:1 for 10 days.
Yaroslavl Regional Clinical Hospital for War Veterans - The International Center for the Elderly "Healthy Longevity"
Yaroslavl, Russia
RECRUITINGWHO Ordinal Scale for Clinical Improvement
The median time to reach the clinical improvement on the WHO Ordinal Scale for Clinical Improvement (follow-up period 28 days after initiation of treatment) using hazard ratio estimates.
Time frame: 28 days
Mortality
All-cause mortality (follow-up period of 28 days after the start of treatment)
Time frame: 28 days
Duration of hospitalization
Duration of hospitalization from the start of therapy, days (observation period of 28 days after the start of treatment)
Time frame: 28 days
Mechanical ventilation
The need for mechanical ventilation, extracorporeal membrane oxygenation, non-invasive ventilation or high-flow oxygen delivery by nasal cannula (observation period of 28 days after the start of treatment).
Time frame: 28 days
Time to cancellation of oxygen support
Time to cancellation of oxygen support, if available, days (observation period of 28 days after the start of treatment)
Time frame: 28 days
Invasive mechanical ventilation
The need for invasive mechanical ventilation of the lungs (observation period of 28 days after the start of treatment)
Time frame: 28 days
Stay in the intensive care unit
The need to stay in the intensive care unit (observation period of 28 days after the start of treatment).
Time frame: 28 days
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The transition of the disease to an extremely severe course
The frequency of the transition of the disease to an extremely severe course (observation period of 28 days after the start of treatment).
Time frame: 28 days
Fever
Duration of fever (≥38оC), days (observation period of 28 days after the start of treatment)
Time frame: 28 days
The dynamics of the National Early Warning Score (NEWS)
The dynamics of the National Early Warning Score (NEWS) decrease in comparison with the baseline value (observation period of 10 days). NEWS uses six physiological measurements: respiratory rate; oxygen saturation; temperature; systolic blood pressure; heart rate and level of consciousness. Each scores 0-3 and individual scores are added together for an overall score. An additional one points are added if the patient is receiving oxygen therapy. Higher scores mean a worse outcome.
Time frame: 10 days
The dynamics of changes in the level of C-reactive protein
The dynamics of changes in the level of C-reactive protein compared with the baseline value (observation period of 10 days).
Time frame: 10 days
The dynamics of residual symptoms
The dynamics of residual symptoms compared to baseline values (observation period of 10 days).
Time frame: 10 days
The dynamics of residual symptoms
The dynamics of residual symptoms on the 28th day after the start of treatment.
Time frame: 28 days
The dynamics of blood biochemical parameters
The dynamics of blood biochemical parameters in comparison with the initial value (observation period of 10 days) Any clinically significant deviations from laboratory parameters detected at visits after the first dosing of the drugs. Biochemical blood assay: urea, creatinine, glucose, alanine aminotransferase, aspartate aminotransferase, bilirubin, albumin, lactate, lactate dehydrogenase, troponin, ferritin. Local laboratories of research centers will be used for laboratory tests and assessments. After collecting and verification 100% values of laboratory parameters according to the Protocol from all local laboratories, the units of measurement will be unified before Statistical process control by valid formulas for transitions.
Time frame: 10 days
The dynamics of CT signs
The dynamics of CT signs on the 14th day after the start of therapy compared with the baseline value. In the conclusion CT study, a probabilistic assessment of the relationship of the detected changes with COVID 19 according to international recommendations and the approximate volume of lung damage according to the "empirical" scale of assessment shall be given. The scale is based on a visual assessment of the approximate volume of compacted lung tissue in both lungs: 1. Absence of characteristic manifestations (CT-0) 2. Minimum volume/site \< 25% of lung volume (CT-1) 3. Average volume/site 25 - 50% of lung volume (CT-2) 4. Significant volume/site 50 - 75% of lung volume (CT-3) 5. Critical volume/site \> 75% of lung volume (CT-4).
Time frame: 14 days