Oral Care With 3% Hydrogen Peroxide (Oroxid®) in ICU - Effects on the Lower Airway Microbial Colonisation

Study Overview
=================
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

Official Title
-----------------
Effects of Oral Care With 3% Hydrogen Peroxide (Oroxid®) on the Lower Respiratory Tract Microbial Colonisation in Mechanically Ventilated Adult Critically Ill Patients (HyPer-MICROBE Trial); a Single-centre, Randomised, Controlled Trial

Conditions
-----------------
VAP - Ventilator Associated Pneumonia

Intervention / Treatment
-----------------
* Drug: Oroxid®
* Drug: Chlorhexidine mouthwash


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥18 years In-patient of ICU and expected to stay > 5 days Mechanical ventilation or imminent need of it; predicted length of mechanical ventilation (MV) ≥ 72h Clinical Pulmonary Infection score (CPIS) less than 6 at the baseline No history and symptoms of aspiration at the baseline Exclusion Criteria: ATB therapy on admission Suspected pulmonary infection on admission and in the first 48h of mechanical ventilation Pregnancy Oral ulcers or injuries Patient with a history of hydrogen peroxide allergy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hydrogen Peroxide<br>Intervention group: daily oral care will be provided according to the local standard, with 3% hydrogen peroxide, oral assessment and teeth brushing will be completed twice daily (morning and evening). | Drug: Oroxid®<br>* 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.<br>* Other names: 3% hydrogen peroxide mouthwash;|
| Active Comparator: Chlorhexidine<br>Control group: daily oral care will be provided according to the local standard, with 0,2% chlorhexidine, oral assessment and teeth brushing will be completed twice daily (morning and evening). | Drug: Chlorhexidine mouthwash<br>* 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<br>* Other names: 0,2% chlorhexidine gluconate;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative incidence of lower respiratory tract microbial colonisation analysed by Kaplan-Maier method, censored in the case of ICU discharge or extubation > 24h. | 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. | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in the relative risk of infection related ventilator associated complications (IVAC) | 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 | 18 months | 
| ATB exposure at discharge | Duration of antibiotics prescribed at discharge | From the date of enrolment through to the date of ICU discharge, approximately 28 days | 
| Intraoral complications, reported using the Bedside oral exam (BOE) score, validated and adopted for ICU. | 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 | will be measured at 24 hours (T1), day 3 (T2), day 7 (T3) and day 14 (T4) after admission | 
| Length of ICU stay in days | that is, length of ICU stay in days | at 3 months | 
| Number of ventilator-free days; | that is, number of days, out of 28 days after admission, that patient has not been supported by mechanical ventilation | at 28 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
pneumonia, hydrogen peroxide, chlorhexidine, respiratory tract microbiome