Clinical Trial to Study the Efficacy and Safety of Fluorothiazinone (N.F. Gamaleya NRCEM) in Prophylaxis of Nosocomial Bacterial Infections With Participation of Patients on MV

Study Overview
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Brief Summary
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This study is designed to evaluate the clinical and antibacterial efficacy, safety and pharmacokinetics of the drug Fluorothiazinone compared to placebo to prevent nosocomial gram-negative bacterial infections with participation of patients on mechanical ventilation. The main objectives of this study are: Evaluation of the clinical and antibacterial efficacy of the drug Fluorothiazinone in combination with standard measures for the prevention of nosocomial infections compared to placebo in combination with standard measures for the prevention of nosocomial infections for the prevention of nosocomial infections caused by bacterial gram-negative flora in patients on mechanical ventilation. Evaluation of the safety and tolerability of the drug Fluorothiazinone in patients on mechanical ventilation. Evaluation of the pharmacokinetics (in whole blood) of the drug Fluorothiazinone with a single daily dose of 2400 mg/day. Researchers will compare results for the treatment and the placebo arms.

Official Title
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A Randomized, Double-blind, Placebo Controlled Clinical Trial to Study the Efficacy and Safety of the Drug Fluorothiazinone (Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation) in Prophylaxis of Nosocomial Bacterial Infections With Participation of Patients on Mechanical Ventilation

Conditions
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Gram Negative Pneumonia, Gram-Negative Bacterial Infections, Bacteremia Caused by Gram-Negative Bacteria

Intervention / Treatment
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* Drug: Fluorothiazinone, tablets 300 mg at a dose of 2400 mg/day
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient's written consent to participate in the study in accordance with the current legislation or the decision of the board in case of absence of consciousness of the patient. Patients are at least 18 years old, male and female. Patients who are in the ICU (intensive care unit). Patients with: 4.1. Laboratory confirmed SARS-CoV-2 (Severe acute respiratory syndrome-related coronavirus-2) on screening (a patient's coronavirus infection can be confirmed either before admission to the hospital (for outpatient treatment) or when admitted to the hospital) by RT-PCR (reverse transcription polymerase chain reaction) AND severe community-acquired pneumonia in ICU with evidence of viral lung injury and symptoms of respiratory failure: SpO2 (peripheral oxygen saturation) ≤ 93%; Lung changes of 3rd- to 4th-degree according to CT (results of computed tomography), consistent with viral involvement; OR 4.2. Acute stroke; OR 4.3. Acute heart failure: Cardiogenic shock of any cause, pulmonary edema, or acute decompensated chronic heart failure. Patients who have been on ALV (artificial lung ventilation) for no more than 12 hours. Patients who are according to the investigator are at high risk to be transferred to ALV within 72 hours of the initiation of the therapy. All women of childbearing age and men with partners of childbearing age should agree to use an effective contraceptive methods (e.g., implants, infections, combination oral contraceptives, intrauterine device, abstinence, vasectomy or vasectomy partner) during the entire study. Exclusion Criteria: The patient was not switched to ALV within 72 hours (3 days) after receiving the investigational drug. People who have a bloodstream infection, identified during the screening. A patient may terminate his/her participation in the study at any time for any reason and without any explanation. 3. The investigator may also decide to terminate the patient's participation at any time if it is required due to the patient's condition. 4. The sponsor or the regulator may also request the trial to be terminated early, either due to how the trial was conducted, or due to application safety data, or other reasons. 5. The main reasons why the patient may withdraw from the study are: Refusal of the patient to participate in the study; Development of an AE (adverse event) / SAE (serious adverse event) that prevents further study participation; The occurrence of concomitant somatic diseases / symptoms or exacerbation of chronic diseases not related to the investigational drug (at the discretion of the medical investigator).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment arm<br> | Drug: Fluorothiazinone, tablets 300 mg at a dose of 2400 mg/day<br>* Treatment arm patients will receive Fluorothiazinone, tablets 300 mg at a dose: 2400 mg/day (4 tablets twice a day) for the first 2 days and; 1800 mg/day (3 tablets twice a day) from the third day and further (but no more than 14 days) until the occurrence of ventilator-associated pneumonia caused by gram-negative bacteria, confirmed clinically and microbiologically, OR the completion of the patient's participation in the study for other reasons. Tablets are taken 2 times a day 12 hours apart 30 minutes after meal, no more than 14 days.<br>|
| Placebo Comparator: Placebo arm<br> | Other: Placebo<br>* Placebo arm patients will receive placebo: 4 tablets twice a day for the first 2 days and; 3 tablets twice a day and further (but no more than 14 days) until the occurrence of ventilator-associated pneumonia caused by gram-negative bacteria, confirmed clinically and microbiologically, OR the completion of the patient's participation in the study for other reasons. Tablets are taken 2 times a day 12 hours apart 30 minutes after meal, no more than 14 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MV-associated pneumonia caused by gram-negative bacteria (72-120 hours from the moment of tracheal intubation and the start of the MV) | The proportion of patients in the study groups without clinically and microbiologically confirmed MV-associated pneumonia caused by gram-negative bacteria, which developed no earlier than 72 hours (3 days) and no later than 120 hours (5 days) from the moment of tracheal intubation and the start of the MV, in the absence of signs of pulmonary infection at the time of intubation. | Throughout the therapy period (14 days). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time from the beginning of the MV to the development of MV-associated pneumonia | The time from the beginning of the MV to the development of MV-associated pneumonia caused by gram-negative bacteria, confirmed clinically and microbiologically, in the study groups during the entire period of therapy. | Throughout the therapy period (14 days). | 
| Time from the beginning of the MV to the development of a bloodstream infection | The time from the beginning of the MV to the development of a bloodstream infection caused by gram-negative bacteria, confirmed microbiologically in the study groups during the entire period of therapy. | Throughout the therapy period (14 days). | 
| Time from the beginning of the MV to the development of urinary tract infection | The time from the beginning of the MV to the development of urinary tract infection caused by gram-negative bacteria, confirmed microbiologically in the study groups during the entire period of therapy. | Throughout the therapy period (14 days). | 
| Proportion of patients who developed urinary tract infection | The proportion of patients who developed urinary tract infection caused by gram-negative bacteria, confirmed microbiologically, in the study groups during the entire period of reception of the investigative drug (IMP). | Throughout the therapy period (14 days). | 
| Proportion of patients who did not develop MV-associated pneumonia | The proportion of patients who did not develop MV-associated pneumonia caused by gram-negative bacteria, confirmed clinically and microbiologically, in the study groups during the entire period of reception of the investigative drug (IMP). | Throughout the therapy period (14 days). | 
| Proportion of patients who have gram-negative bacteria | The proportion of patients who have gram-negative bacteria isolated from the respiratory tract, with no clinical picture of pneumonia. | Throughout the therapy period (14 days). | 
| Proportion of patients who developed a bloodstream infection (during the entire period of therapy) | The proportion of patients who developed a bloodstream infection caused by gram-negative microflora, confirmed microbiologically in the study groups during the entire period of therapy. | Throughout the therapy period (14 days). | 
| Proportion of patients who developed a bloodstream infection (after the patient was transferred to the MV) | The proportion of patients who developed a bloodstream infection caused by gram-negative microflora, confirmed microbiologically in the study groups after the patient was transferred to the MV. | Throughout the therapy period (14 days). | 
| Proportion of patients with septic complications | The proportion of patients with septic complications in the study groups during the entire period of therapy. | Throughout the therapy period (14 days). | 
| The proportion of fatal outcomes | The proportion of fatal outcomes in the study groups during the entire period of therapy. | Throughout the therapy period (14 days). |