Clinical trial NCT06135350: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Gram Negative Pneumonia
Gram-Negative Bacterial Infections
Bacteremia Caused by Gram-Negative Bacteria
Lead sponsor: Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation
Sponsor class: OTHER
First posted: 2023-11-18
Enrollment: 234
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. 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.
2. Patients are at least 18 years old, male and female.
3. Patients who are in the ICU (intensive care unit).
4. 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.
5. Patients who have been on ALV (artificial lung ventilation) for no more than 12 hours.
6. 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.
7. 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:

1. The patient was not switched to ALV within 72 hours (3 days) after receiving the investigational drug.
2. People who have a bloodstream infection, identified during the screening.
3. 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).

Primary outcomes:
measure: MV-associated pneumonia caused by gram-negative bacteria (72-120 hours from the moment of tracheal intubation and the start of the MV)
timeFrame: Throughout the therapy period (14 days).
Secondary outcomes:
measure: Time from the beginning of the MV to the development of MV-associated pneumonia
timeFrame: Throughout the therapy period (14 days).
measure: Time from the beginning of the MV to the development of a bloodstream infection
timeFrame: Throughout the therapy period (14 days).
measure: Time from the beginning of the MV to the development of urinary tract infection
timeFrame: Throughout the therapy period (14 days).
measure: Proportion of patients who developed urinary tract infection
timeFrame: Throughout the therapy period (14 days).
measure: Proportion of patients who did not develop MV-associated pneumonia
timeFrame: Throughout the therapy period (14 days).
measure: Proportion of patients who have gram-negative bacteria
timeFrame: Throughout the therapy period (14 days).
measure: Proportion of patients who developed a bloodstream infection (during the entire period of therapy)
timeFrame: Throughout the therapy period (14 days).
measure: Proportion of patients who developed a bloodstream infection (after the patient was transferred to the MV)
timeFrame: Throughout the therapy period (14 days).
measure: Proportion of patients with septic complications
timeFrame: Throughout the therapy period (14 days).
measure: The proportion of fatal outcomes
timeFrame: Throughout the therapy period (14 days).
Other outcomes:
measure: Comparative characteristics of colonization of the respiratory and urinary tracts
timeFrame: Throughout the therapy period (14 days).
measure: Comparative assessment of the condition on the SOFA scale
timeFrame: Throughout the therapy period (14 days).
measure: Comparative assessment of the condition on the APACHE II scale
timeFrame: Throughout the therapy period (14 days).
Locations:
city: Moscow
country: Russian Federation
facility: State Budgetary Healthcare Institution of Moscow City Clinical Hospital No. 1 named after N.I. Pirogov of the Moscow Department of Health (State Clinical Hospital No. 1 named after N.I. Pirogov)
city: Moscow
country: Russian Federation
facility: City Clinical Hospital No. 24 of the Moscow City Department of Health
Study officials:
References: