VAP - Ventilator Associated Pneumonia
Conditions
Keywords
pneumonia, hydrogen peroxide, chlorhexidine, respiratory tract microbiome
Brief summary
HyPerMICROBE is a single-centre, controlled, randomised, prospective, superiority clinical trial to compare the efficacy of daily oral care with 3% hydrogen peroxide (Oroxid®) versus standard of care (0.2% chlorhexidine digluconate) on the cumulative incidence of lower respiratory tract microbial colonisation in mechanically ventilated adult critically ill patients.
Detailed description
Rationale: Ventilator-associated pneumonia (VAP) is the most common hospital-acquired infection (HAI) in the intensive care unit (ICU), and its impact is very high in terms of morbidity, length of hospital stay and overall costs. Chlorhexidine for oral care in critically ill has no clear impact on VAP rates and may cause harm. 3% hydrogen peroxide (Oroxid) could be a promising substitute. Aim: To test effectivity and safety of 3% hydrogen peroxide solution on ventilator-associated complications Design: Prospective, single center, parallel group randomised controlled trial. Subjects: ICU patients (general ICU) Treatment in the intervention group: daily oral care with 3% hydrogen peroxide Control group: Standard-of-care protocolised daily oral care with 0,2% chlorhexidine Primary outcome: Cumulative incidence of lower respiratory tract microbial colonisation analysed by Kaplan-Maier method, censored in the case of ICU discharge or extubation \> 24h. Secondary and exploratory outcomes: Differences in the relative risk of infection related ventilator-associated complications, antibiotic (ATB) consumption analysis, intraoral complications, reported using the Bedside oral exam (BOE) score, validated and adopted for ICU, length of ICU stay in days (time frame: at 3 months), number of ventilator-free days (time frame: at 28 days); that is, number of days, out of 28 days after admission, that patient has not been supported by mechanical ventilation
Interventions
DRUGOroxid®
All patients in experimental arm will receive usual best medical and nursing care with respect to VAP prevention including recently reviewed local ventilator bundle ; standard microbial surveillance (tracheal aspirate) will be performed twice a week (Monday, Thursday) and always ad hoc according to the clinical situation. This reflects current practice. Daily oral care will be provided using Oroxid® mouthwash.
DRUGChlorhexidine mouthwash
All patients in experimental arm will receive usual best medical and nursing care with respect to VAP prevention including recently reviewed local ventilator bundle ; standard microbial surveillance (tracheal aspirate) will be performed twice a week (Monday, Thursday) and always ad hoc according to the clinical situation. This reflects current practice. Daily oral care will be provided using 0,2% chlorhexidine
Sponsors
Charles University, Czech Republic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Investigator, Outcomes Assessor)
Masking description
Due to the nature of the intervention nurses can't be blinded to allocation (the mouthwash type - nature of the fluid, its odour etc.), but are strongly inculcated not to disclose the allocation status of the participant at the follow up assessments. As the ICU is paperless and fully computerised, the data in the computer can be acquired and analysed by the researchers without having access to information about the allocation.
Intervention model description
Eligible patients will be recruited in medical-surgical ICU at Kralovske Vinohrady University Hospital (FNKV), managed under an intensivist-led closed ICU, with a 1:1 nurse-to-patient ratio and randomised in equal proportions between 3% hydrogen peroxide arm and 0,2% chlorhexidine digluconate arm.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 years 2. In-patient of ICU and expected to stay \> 5 days 3. Mechanical ventilation or imminent need of it; predicted length of mechanical ventilation (MV) ≥ 72h 4. Clinical Pulmonary Infection score (CPIS) less than 6 at the baseline 5. No history and symptoms of aspiration at the baseline
Exclusion criteria
1. ATB therapy of respiratory infection on admission 2. Suspected pulmonary infection on admission and in the first 48h of mechanical ventilation 3. Pregnancy 4. Oral ulcers or injuries 5. Patient with a history of hydrogen peroxide allergy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative incidence of lower respiratory tract microbial colonisation analysed by Kaplan-Maier method, censored in the case of ICU discharge or extubation > 24h. | 18 months | To detect microorganisms in the lower respiratory tract, tracheal aspirate will be directly cultured for detecting Gram-positive, Gram-negative, and anaerobic bacteria and fungi. Standard microbial surveillance (tracheal aspirate) will be performed on admission, twice a week (Monday, Thursday) and always ad hoc according to the clinical situation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ATB exposure at discharge | From the date of enrolment through to the date of ICU discharge, approximately 28 days | Duration of antibiotics prescribed at discharge |
| Intraoral complications, reported using the Bedside oral exam (BOE) score, validated and adopted for ICU. | will be measured at 24 hours (T1), day 3 (T2), day 7 (T3) and day 14 (T4) after admission | BOE score ranges from 8 (excellent oral health) to 24 (poor oral health). The BOE scores ranging from 8-10 are considered as indicative of excellent oral health, from 11-14 as moderately impaired oral health and from 15-24 as significantly impaired oral health |
| Length of ICU stay in days | at 3 months | that is, length of ICU stay in days |
| Number of ventilator-free days; | at 28 days | that is, number of days, out of 28 days after admission, that patient has not been supported by mechanical ventilation |
| Differences in the relative risk of infection related ventilator associated complications (IVAC) | 18 months | According to the Centers for Disease Control and Prevention (CDC) criteria, the IVAC diagnosis will be established based on: * an increase of the daily minimum positive end-expiratory pressure (PEEP) of ≥3 cm H2O and/or the daily minimum inspired oxygen fraction (FiO2) of ≥20 points sustained for ≥2 days and * an evidence of a new infection present (abnormal temperature or white blood cell count) and prescription of a new antibiotic for ≥4 days |
Other
| Measure | Time frame | Description |
|---|---|---|
| The number of participants with Non-pulmonary infections | up to 30 days | The number of participants with Non-pulmonary infections |
| Antibiotic Free Days | up to 30 days | The number of days where participant did not require the use of antibiotics |
| Composition of the oral and lower airway microbiome between groups measured by the bacterial 16S rRNA sequencing | day 0, day 7 and day 14 | Microbial DNA will be sequentially (on admission, day 3, 7 and 14) sampled and isolated from prespecified sites in oral cavity, hypopharynx and lower respiratory tract. Microbial DNA will be analyzed by 16S rRNA amplicon sequencing and quantified by multiplex qPCR method. Paired comparison of bacteriomes between intervention group and control group will be performed to identify potentially risky host bacteriome profiles. |
Countries
Czechia
Contacts
Primary ContactKateřina Rambousková, MD
Backup ContactAdela Jiroudkova
Outcome results
None listed