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

Sepsis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04839653
• Other study ID #: SDDMEDSI2021
• Status: Recruiting
• Phase: N/A
• Start date: May 1, 2021
• Est. completion date: April 2023

Study information

• Verified date: June 2021
• Source: MEDSI Clinical Hospital 1, ICU
• Contact: Yury Surovoy, MD
• Phone: +79166911507
• Email: ysurovoy[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: April 2023
• Est. primary completion date: April 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Bloodstream Infection
• Communicable Diseases
• Critical Illness
• Infection
• Pneumonia
• Pneumonia, Ventilator-Associated
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn
• Respiratory Tract Infections
• Sepsis

Intervention

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.
• 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.
• 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

Locations

Country	Name	City	State
Russian Federation	MEDSI Clinical Hospital 1	Moscow

Sponsors (1)

Lead Sponsor	Collaborator
MEDSI Clinical Hospital 1, ICU

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	The incidence of bloodstream infections	Number of bloodstream infection events per 1000 days of ICU stay	During ICU stay up to 28 days
Secondary	ICU mortality	All-cause mortality	During ICU stay up to 28 days
Secondary	Duration of mechanical ventilation	The duration that the patient receives mechanical ventilation in the ICU	During ICU stay up to 28 days
Secondary	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
Secondary	Antimicrobial drug consumption	Average antimicrobial drug consumption (as daily defined doses) per patient stay	During ICU stay up to 28 days
Secondary	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