Clinical trial NCT04780672: Clinical Study in the Treatment of Patients With COVID-19
Official title: Clinical Study to Analyze the Safety and Efficacy of Molixan® as Part of Standard Therapy in the Treatment of Patients With the Severe Course of New Coronavirus Infection (COVID-19)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: COVID-19
Keywords: COVID-19
METABOLIC DRUG
Severe course of COVID-19
Lead sponsor: Pharma VAM
Sponsor class: OTHER
First posted: 2021-03-03
Enrollment: 330
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Hospitalized male and female patients aged 18 to 75 and weighing no more than 120 kg inclusively with a diagnosis of the severe course of COVID-19 confirmed by the result of a laboratory study for the presence of SARS-CoV-2 RNA using nucleic acid amplification methods (to be performed on Screening, or results with sampling 72 hours prior to Screening may be accepted);
2. Changes in the lungs on CT (X-ray) typical for viral damage (the damage size is significant or subtotal; CT 3-4);
3. One or more criteria for a severe course:

   * RR \> 30/min
   * SpO2 ≤ 93%
   * PaO2 /FiO2 ≤ 300 mm Hg
   * Decreased consciousness, agitation
   * Unstable hemodynamics (systolic blood pressure less than 90 mm Hg or diastolic blood pressure less than 60 mm Hg, urine output less than 20 ml/hour)
   * Arterial blood lactate \> 2 mmol/l
   * qSOFA \> 2 points
4. Signed informed consent of the patient to participate in the study\*;
5. The patient's ability to adequately cooperate (the ability to understand the information provided about the clinical study, the willingness to comply with the requirements of the study protocol)\*;

   \*In case of impossibility of the criteria No. 4 and 5 fulfilling the decision on including the patient shall be taken by a medical council. After the normalization of the status the patient shall compulsorily be proposed to acquaint themselves with the Patient Information Leaflet and take a decision on further participation in the study (Informed Consent Form signing) or withdrawal.
6. For women with preserved reproductive function - a negative pregnancy test and consent to use adequate methods of contraception from the moment of inclusion in the study until the end of the study;
7. For men - consent to use adequate methods of contraception from the moment of inclusion in the study to the end of the study.

Non-inclusion criteria:

Patients cannot be included in the study if at least one of the following criteria is met:

Associated with the underlying disease:

1. Mild, moderate and extremely severe COVID-19 disease upon admission to the hospital;
2. A condition requiring invasive oxygen support;
3. Failure to meet the criteria for inclusion and severity of the condition in terms of the main parameters;

   Related to the investigational drug, prior and concomitant therapy:
4. Hypersensitivity or individual intolerance to the components of the investigational drug according to the history;
5. Taking any antiviral or immunomodulatory drugs after the manifestation of COVID-19 (except for those planned for appointment as part of the study);

   Associated with concomitant pathology:

   According to the history and physical examination:
6. A history of active tuberculosis;
7. Impossibility of intravenous administration of the drug;
8. Severe, decompensated or unstable somatic diseases according to the history and outpatient card/medical history:

   * Child-Pugh class B and C cirrhosis;
   * Myocardial infarction, CVA/TIA, PE less than 3 months before the start of the study, large aortic aneurysm (more than 6 cm);
   * Type 1 diabetes mellitus. Diseases of the thyroid gland with decompensation.
   * The presence of signs of severe damage to the central nervous system (history of severe TBI, meningitis, consequences of CVA, encephalopathy of various origin, epilepsy, etc.);
   * Current severe blood disorders or history of such diseases (i.e. baseline anemia Hb\<80, myeloid leukemia, myelodysplastic syndrome, etc.);
   * No less than 3 months after the surgery for coronary artery bypass grafting/stenting before inclusion in the study;
   * Malignant neoplasm of any localization at present or within 5 years prior to inclusion in the study, with the exception of completely healed carcinoma in situ;
9. Any other comorbidities or conditions that, in the opinion of the investigator, make it difficult to interpret the results of treatment or may limit the patient's participation in the study;

   According to laboratory tests at screening:
10. A positive result for HIV, syphilis, hepatitis B and C at screening;

    Associated with the patient compliance in the study:
11. A history of alcohol abuse, drug dependence or drug addiction;
12. Patients who, in the opinion of the investigator, are obviously or likely to be unable to understand and evaluate the information on this study as part of the informed consent signing process, in particular regarding the expected risks and possible discomfort;
13. Patient's inability or unwillingness to follow the rules for conducting and participating in the clinical study;
14. Severe visual and/or hearing impairments, severe speech impairments and/or other abnormalities that may prevent the patient from adequately cooperating during the study;
15. A history of mental illness;

    Other:
16. Pregnancy;
17. Breast-feeding;
18. Participation in other clinical studies within 3 months prior to enrollment in this study.

Exclusion Criteria:

1. Erroneous inclusion (violation of inclusion/non-inclusion criteria).
2. Individual intolerance to the investigational drug.
3. Refusal of the patient to continue participating in the study/withdrawal of informed consent by the patient.
4. Termination of the study.

Primary outcomes:
measure: WHO Ordinal Scale for Clinical Improvement
timeFrame: 28 days
Secondary outcomes:
measure: Mortality
timeFrame: 28 days
measure: Duration of hospitalization
timeFrame: 28 days
measure: Mechanical ventilation
timeFrame: 28 days
measure: Time to cancellation of oxygen support
timeFrame: 28 days
measure: Invasive mechanical ventilation
timeFrame: 28 days
measure: Stay in the intensive care unit
timeFrame: 28 days
measure: The transition of the disease to an extremely severe course
timeFrame: 28 days
measure: Fever
timeFrame: 28 days
measure: The dynamics of the National Early Warning Score (NEWS)
timeFrame: 10 days
measure: The dynamics of changes in the level of C-reactive protein
timeFrame: 10 days
measure: The dynamics of residual symptoms
timeFrame: 10 days
measure: The dynamics of residual symptoms
timeFrame: 28 days
measure: The dynamics of blood biochemical parameters
timeFrame: 10 days
measure: The dynamics of CT signs
timeFrame: 14 days
Other outcomes:
Locations:
city: Yaroslavl
country: Russian Federation
facility: Yaroslavl Regional Clinical Hospital for War Veterans - The International Center for the Elderly "Healthy Longevity"
Study officials:
affiliation: Federal State Budgetary Educational Institution of Higher Education
name: Viktor Borisovich Filimonov
role: PRINCIPAL_INVESTIGATOR
affiliation: Federal Siberian Scientific and Clinical Center of the Federal Medical and Biological Agency, Krasnoyarsk
name: Tamara Valerievna Gaigolnik
role: PRINCIPAL_INVESTIGATOR
affiliation: Federal State Budgetary Educational Institution of Higher Education "Bashkir State Medical University" of the Ministry of Healthcare of the Russian Federation
name: Halida Hanafievna Ganceva
role: PRINCIPAL_INVESTIGATOR
affiliation: State Budgetary Institution of Healthcare of Moscow Region "Zhukovskaya City Clinical Hospital", Zhukovskiy, Moscow Region, Russian Federation
name: Elena Petrovna Dmitrikova
role: PRINCIPAL_INVESTIGATOR
affiliation: Yaroslavl Regional Clinical Hospital for War Veterans - The International Center for the Elderly "Healthy Longevity"
name: Mariya Evgen'evna Mozhejko
role: PRINCIPAL_INVESTIGATOR
affiliation: Republican Clinical Infectious Diseases Hospital named after professor Agafonov
name: Halit Saubanovich Haertynv
role: PRINCIPAL_INVESTIGATOR
affiliation: State Budgetary Healthcare Institution "Research Institute - Regional Clinical Hospital No. 1 named after Professor S. V. Ochapovsky" of the Ministry of Health of the Krasnodar Territory
name: Zoya Gennad'evna Tatarinceva
role: PRINCIPAL_INVESTIGATOR
affiliation: Regional State Budgetary Healthcare Institution "Smolensk Regional Clinical Hospital"
name: Aleksandr Alekseevich Punin
role: PRINCIPAL_INVESTIGATOR
affiliation: Federal State Budgetary Educational Institution of Higher Education "Samara State Medical University" of the Ministry of Healthcare of the Russian Federation
name: Dmitrij YUr'evich Konstantinov
role: PRINCIPAL_INVESTIGATOR
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