Efficacy and Safety of Selective Digestive Decontamination in the ICU With High Rates of Antibiotic-resistant Bacteria

Not Applicable

• Conditions: Pneumonia, Ventilator-Associated; Pneumonia; Critical Illness; Bloodstream Infection; Sepsis; Respiratory Distress Syndrome; Respiratory Tract Infections
• Interventions: Drug: Oral Paste(0,5 g) containing 10 mg of polymyxin B, 10 mg of gentamycin and 150 mg of amphotericine B or 500 000 U of nistatin q6h; Drug: Suspension (10 ml) containing 100 mg of polymyxin B, 80 mg of gentamycin, 350 mg of amphotericine B or 8000000 U of nistation and 500 mg of vancomycin q6h; Drug: Intravenous Antibacterial Agent - a 3-day course of systemic cefotaxime 1 g q6h or ceftriaxone 1 g qd

• Registration Number: NCT04839653
• Lead Sponsor: MEDSI Clinical Hospital 1, ICU

Brief Summary

Secondary infections remain a major cause of mortality in critically ill patients, mainly because of high prevalence of multidrug-resistant microorganisms. Therefore strategies aimed to reduce the incidence of ventilator-associated pneumoniae (VAP) and bloodstream infections are of utmost important. There is robust data on selective digestive decontamination (SDD) efficacy in reduction of secondary infections in intensive care units (ICU) with low rates of antibacterial resistance. However the data received from hospitals with moderate-to-high rates of resistance is equivocal.

This as an interventional parallel open-label study investigating the effect of selective digestive decontamination on the rates of ventilator-associated pneumonia in critically ill patients admitted to the ICU with high prevalence of drug-resistant bacteria. Secondary outcomes include rates of bloodstream infections, mortality, duration of mechanical ventilation, duration of ICU stay, resistance selection and overall antibiotic consumption.

Detailed Description

Single-center prospective interventional parallel study. During the first period of the study patients will receive standard therapy. During the second period the SDD protocol will be implemented in addition to the standard care. The first period will end at the moment of the last admitted patient ICU discharge or death.

Study population: general ICU adult patients anticipated to receive prolonged mechanical ventilation (more than 48 hours). Patients who are terminally ill and are anticipated to die in the next 24 hours will be excluded, so are patients with malignancies (except for patients with primary central nervous system tumors who received radical treatment) and patients admitted from other hospitals who received mechanical ventilation (including non-invasive ventilation) for more than 24 hours.

Patients in the interventional arm will receive the following SDD protocol:

1. Oral paste (0,5 g) containing 10 mg of polymyxin B, 10 mg of gentamycin and 150 mg of amphotericine B/500000 U of nistatin q6h

2. In the nasogastric tube (NGT) 10 ml of suspension containing 100 mg of polymyxin B, 80 mg of gentamycin, 350 mg of amphotericine B/8000000 U of nistatin and 500 mg of vancomycin q6h

3. A 3-day course of intravenous cefotaxime 1 g q6h/ceftriaxone 1 qd

Statistical considerations and recruitment plant: VAP incidence in the ICU with high rates of antibacterial resistance is 16,7 event per 1000 days of MV. To reveal a 25% decrease of VAP events (power 80%, p \< 0,05) the study should recruit 25 patients in each group. However because of the poor prognosis in mechanically ventilated elderly patients especially in the setting of acute respiratory distress syndrome the goal is to recruit in each arm at least 25 patients younger than 65 years.

Study Timeline

• Study First Submitted: 2021-04-05
• Study First Submitted QC: 2021-04-07
• Study First Posted: 2021-04-09
• Study Start: 2021-05-01
• Status Verified: 2021-06
• Last Update Submitted: 2021-06-03
• Last Update Posted: 2021-06-08
• Primary Completion: 2022-04
• Study Completion: 2023-04

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• Patients with expected MV for more than 24 hours

Exclusion Criteria

• Moribund condition and expected death within 24 hours
• Malignancy (excluding primary CNS tumors)
• Patients transferred from other hospitals who were mechanically ventilated for more than 24 hours (including NIV)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Selective digestive decontamination group	Oral Paste(0,5 g) containing 10 mg of polymyxin B, 10 mg of gentamycin and 150 mg of amphotericine B or 500 000 U of nistatin q6h	1. Oral paste (0,5 g) containing 10 mg of polymyxin B, 10 mg of gentamycin and 150 mg of amphotericine B q6h 2. In the NGT 10 ml of suspension containing 100 mg of polymyxin B, 80 mg of gentamycin, 350 mg of amphotericine B and 500 mg of vancomycin q6h 3. A 3-day course of intravenous cefotaxime 1 g q6h/ceftriaxone 1 qd
Selective digestive decontamination group	Suspension (10 ml) containing 100 mg of polymyxin B, 80 mg of gentamycin, 350 mg of amphotericine B or 8000000 U of nistation and 500 mg of vancomycin q6h	1. Oral paste (0,5 g) containing 10 mg of polymyxin B, 10 mg of gentamycin and 150 mg of amphotericine B q6h 2. In the NGT 10 ml of suspension containing 100 mg of polymyxin B, 80 mg of gentamycin, 350 mg of amphotericine B and 500 mg of vancomycin q6h 3. A 3-day course of intravenous cefotaxime 1 g q6h/ceftriaxone 1 qd
Selective digestive decontamination group	Intravenous Antibacterial Agent - a 3-day course of systemic cefotaxime 1 g q6h or ceftriaxone 1 g qd	1. Oral paste (0,5 g) containing 10 mg of polymyxin B, 10 mg of gentamycin and 150 mg of amphotericine B q6h 2. In the NGT 10 ml of suspension containing 100 mg of polymyxin B, 80 mg of gentamycin, 350 mg of amphotericine B and 500 mg of vancomycin q6h 3. A 3-day course of intravenous cefotaxime 1 g q6h/ceftriaxone 1 qd

Primary Outcome Measures

Name	Time	Method
The incidence of ventilator-associated pneumonia	During ICU stay up to 28 days	Number of ventilator-associated pneumonia events per 1000 days of MV

Secondary Outcome Measures

Name	Time	Method
The incidence of bloodstream infections	During ICU stay up to 28 days	Number of bloodstream infection events per 1000 days of ICU stay
ICU mortality	During ICU stay up to 28 days	All-cause mortality
Duration of mechanical ventilation	During ICU stay up to 28 days	The duration that the patient receives mechanical ventilation in the ICU
Duration of organ support	During ICU stay up to 28 days	The duration that the patient receives mechanical ventilation, vasopressor infusion or renal-replacement therapy
Antimicrobial drug consumption	During ICU stay up to 28 days	Average antimicrobial drug consumption (as daily defined doses) per patient stay
Antimicrobial resistance selection	During ICU stay up to 28 days	The magnitude of antimicrobial resistance selection in terms of resistant microorganisms prevalence and whole burden of AMR genes

Trial Locations

Locations (1)

MEDSI Clinical Hospital 1; 🇷🇺 Moscow, Russian Federation