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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: VAP - Ventilator Associated Pneumonia
• Intervention / Treatment: Drug: Oroxid®; Drug: Chlorhexidine mouthwash

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

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hydrogen Peroxide; 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®; 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.; Other Names: 3% hydrogen peroxide mouthwash
Active Comparator: Chlorhexidine; 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; 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; 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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composition of the oral and lower airway microbiome between groups measured by the bacterial 16S rRNA sequencing	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.	day 0, day 7 and day 14
Antibiotic Free Days	The number of days where participant did not require the use of antibiotics	up to 30 days
The number of participants with Non-pulmonary infections	The number of participants with Non-pulmonary infections	up to 30 days

Collaborators and Investigators

• Sponsor: Charles University, Czech Republic

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2023
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: August 24, 2023
• First Submitted That Met QC Criteria: September 19, 2023
• First Posted (Actual): September 21, 2023

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 19, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: pneumonia; chlorhexidine; hydrogen peroxide; respiratory tract microbiome
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Cross Infection; Iatrogenic Disease; Healthcare-Associated Pneumonia; Infections; Communicable Diseases; Pneumonia; Pneumonia, Ventilator-Associated; Anti-Infective Agents, Local; Anti-Infective Agents; Dermatologic Agents; Disinfectants; Chlorhexidine; Hydrogen Peroxide; Chlorhexidine gluconate
• Other Study ID Numbers: VP/46/0/2022

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