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

Official title

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

Overview

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.

Interventions

• Drug Fluorothiazinone, tablets 300 mg at a dose of 2400 mg/day
  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 ap
• Other Placebo
  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.

Primary outcome measures

• MV-associated pneumonia caused by gram-negative bacteria (72-120 hours from the moment of tracheal intubation and the start of the MV) [Time frame: Throughout the therapy period (14 days).]

Secondary outcome measures (10)

• Time from the beginning of the MV to the development of MV-associated pneumonia [Time frame: Throughout the therapy period (14 days).]
• Time from the beginning of the MV to the development of a bloodstream infection [Time frame: Throughout the therapy period (14 days).]
• Time from the beginning of the MV to the development of urinary tract infection [Time frame: Throughout the therapy period (14 days).]
• Proportion of patients who developed urinary tract infection [Time frame: Throughout the therapy period (14 days).]
• Proportion of patients who did not develop MV-associated pneumonia [Time frame: Throughout the therapy period (14 days).]
• Proportion of patients who have gram-negative bacteria [Time frame: Throughout the therapy period (14 days).]
• Proportion of patients who developed a bloodstream infection (during the entire period of therapy) [Time frame: Throughout the therapy period (14 days).]
• Proportion of patients who developed a bloodstream infection (after the patient was transferred to the MV) [Time frame: Throughout the therapy period (14 days).]
• Proportion of patients with septic complications [Time frame: Throughout the therapy period (14 days).]
• The proportion of fatal outcomes [Time frame: Throughout the therapy period (14 days).]

Eligibility criteria

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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Prevention

Study locations

Russia · 2 centers

• State Budgetary Healthcare Institution of Moscow City Clinical Hospital No. 1 named after — Moscow
• City Clinical Hospital No. 24 of the Moscow City Department of Health — Moscow

Identifiers

NCT: NCT06135350 · 06-FT-2021, v. 3.0, 03.11.2022

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗