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

• ClinicalTrials.gov Identifier: NCT06045429
• Recruitment Status: Not yet recruiting
• First Posted: September 21, 2023
• Sponsor: Charles University, Czech Republic
• Information provided by (Responsible Party): Kateřina Jiroutková, Charles University, Czech Republic

Study Description

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.

Condition or disease	Intervention/treatment	Phase
VAP - Ventilator Associated Pneumonia	Drug: Oroxid®; Drug: Chlorhexidine mouthwash	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 160 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• 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.
• 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.
• Primary Purpose: Prevention
• 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
• Estimated Study Start Date: May 2024
• Estimated Primary Completion Date: June 2025
• Estimated Study Completion Date: December 2025

Arms and Interventions

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 Name: 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 Name: 0,2% chlorhexidine gluconate

Outcome Measures

Primary Outcome Measures :

1. Cumulative incidence of lower respiratory tract microbial colonisation analysed by Kaplan-Maier method, censored in the case of ICU discharge or extubation > 24h. [ Time Frame: 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 Outcome Measures :

1. Differences in the relative risk of infection related ventilator associated complications (IVAC) [ Time Frame: 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
2. ATB exposure at discharge [ Time Frame: From the date of enrolment through to the date of ICU discharge, approximately 28 days ]
   Duration of antibiotics prescribed at discharge
3. Intraoral complications, reported using the Bedside oral exam (BOE) score, validated and adopted for ICU. [ Time Frame: 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
4. Length of ICU stay in days [ Time Frame: at 3 months ]
   that is, length of ICU stay in days
5. 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

Other Outcome Measures:

1. Composition of the oral and lower airway microbiome between groups measured by the bacterial 16S rRNA sequencing [ Time Frame: 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.
2. Antibiotic Free Days [ Time Frame: up to 30 days ]
   The number of days where participant did not require the use of antibiotics
3. The number of participants with Non-pulmonary infections [ Time Frame: up to 30 days ]
   The number of participants with Non-pulmonary infections

Eligibility Criteria

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

Criteria

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

Contacts and Locations

No Contacts or Locations Provided

More Information

• Responsible Party: Kateřina Jiroutková, Principal Investigator, Kateřina Jiroutková, MD, PhD, EDAIC, Charles University, Czech Republic
• ClinicalTrials.gov Identifier: NCT06045429
• Other Study ID Numbers: VP/46/0/2022
• First Posted: September 21, 2023
• Last Update Posted: April 30, 2024
• Last Verified: April 2024

• 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

Keywords provided by Kateřina Jiroutková, Charles University, Czech Republic:

pneumonia; hydrogen peroxide; chlorhexidine; respiratory tract microbiome

Additional relevant MeSH terms:

Pneumonia; Pneumonia, Ventilator-Associated; Communicable Diseases; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Healthcare-Associated Pneumonia; Cross Infection; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Chlorhexidine; Chlorhexidine gluconate; Hydrogen Peroxide; Anti-Infective Agents, Local; Anti-Infective Agents; Disinfectants; Dermatologic Agents