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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Respiratory Tract Infections; Pneumonia; Sepsis; Critical Illness; Respiratory Distress Syndrome; Pneumonia, Ventilator-Associated; Bloodstream Infection
• Intervention / Treatment: 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

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 Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yury Surovoy, MD; Phone Number: +79166911507; Email: ysurovoy@gmail.com
• Study Contact Backup: Name: Armen Oganesyan, MD; Email: oganesyan.av@medsigroup.ru

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 143442
    • Recruiting
    • MEDSI Clinical Hospital 1
    • Contact: Armen Oganesyan; Email: oganesyan.av@medsigroup.ru
    • Contact: Yury Surovoy; Email: ysurovoy@gmail.co

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control group: standard care; Patients in the standard care group will be prospectively evaluated to determine pre-defined clinical outcomes.
Experimental: 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 q6h; 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; A 3-day course of intravenous cefotaxime 1 g q6h/ceftriaxone 1 qd	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; The oral paste will be applied topically on the oropharyngeal mucosa q6h.; Other Names: Polymyxin B, Gentamycin, Amphotericine B, Nistatin; 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; The suspension will be administered through the nasogastric tube q6h.; Other Names: Polymyxin B, Gentamycin, Amphotericine B, Vancomycine, Nistatin; Drug: Intravenous Antibacterial Agent - a 3-day course of systemic cefotaxime 1 g q6h or ceftriaxone 1 g qd; Patients who do not receive systemic antibiotics for other reasons will get a short course of systemic antibiotic; Other Names: Cefotaxime, Ceftriaxone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of ventilator-associated pneumonia	Number of ventilator-associated pneumonia events per 1000 days of MV	During ICU stay up to 28 days

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: MEDSI Clinical Hospital 1, ICU
• Investigators: Principal Investigator: Dmitry Azovskiy, MD, phD, MEDSI Clinical Hospital 1

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2021
• Primary Completion (Anticipated): April 1, 2022
• Study Completion (Anticipated): April 1, 2023

Study Registration Dates

• First Submitted: April 5, 2021
• First Submitted That Met QC Criteria: April 7, 2021
• First Posted (Actual): April 9, 2021

Study Record Updates

• Last Update Posted (Actual): June 8, 2021
• Last Update Submitted That Met QC Criteria: June 3, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Pneumonia; Infection prophylaxis; Ventilator-Associated Pneumonia; Bloodstream Infection; Selective Digestive Decontamination; Secondary Infections
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Disease Attributes; Infant, Newborn, Diseases; Cross Infection; Iatrogenic Disease; Infant, Premature, Diseases; Healthcare-Associated Pneumonia; Sepsis; Infections; Communicable Diseases; Pneumonia; Critical Illness; Respiratory Tract Infections; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Pneumonia, Ventilator-Associated; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Protein Synthesis Inhibitors; Antifungal Agents; Antiprotozoal Agents; Antiparasitic Agents; Amebicides; Vancomycin; Ceftriaxone; Anti-Bacterial Agents; Gentamicins; Amphotericin B; Liposomal amphotericin B; Polymyxins; Polymyxin B; Cefotaxime; Cefoxitin
• Other Study ID Numbers: SDDMEDSI2021

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No