Oral Bacterial ColonizationNCT07868549
Effects of Three Oral Hygiene Protocols on Oral Bacteria in Intensive Care Patients
A study testing Mechanical Oral Hygiene, Chlorhexidine and Hexetidine in people with Oral Bacterial Colonization and Oral Hygiene, run by University of Zagreb at 1 site in Croatia.
Trial summary
Patients in intensive care may develop changes in the bacteria found in their mouths. Some of these bacteria can cause infections, and patients who cannot clean their own teeth depend on staff to provide oral care. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Oral Bacterial Colonization, Oral Hygiene
- What is being tested?
- Mechanical Oral Hygiene, Chlorhexidine and Hexetidine
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 86 participants
- Where
- 1 siteCroatia
- Study dates
- 1 Jun 2026to 31 Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Admission to the medical intensive care unit of Sestre milosrdnice University Hospital Center, Zagreb, Croatia, for pneumonia, exacerbation of chronic obstructive pulmonary disease, pulmonary embolism, or cardiac decompensation.
- Expected survival longer than 72 hours.
- Written informed consent provided by the patient or an authorized representative.
- Patients of either sex are eligible, regardless of age. Patients receiving or not receiving antibiotic therapy may participate. Patients breathing spontaneously or receiving noninvasive or invasive mechanical ventilation are eligible.
Who cannot join
- Allergy to chlorhexidine or hexetidine.
- Treatment with immunosuppressive agents or corticosteroids.
- Previous radiotherapy to the head and neck region.
- Presence of oral mucosal lesions at the baseline examination.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Comparison of the Effect of Three Oral Hygiene Protocols on Gram-Negative Microbiota in Patients Treated in an Intensive Care Unit
Patients in intensive care may develop changes in the bacteria found in their mouths. Some of these bacteria can cause infections, and patients who cannot clean their own teeth depend on staff to provide oral care.
This study compares three oral hygiene protocols to assess their effects on potentially harmful bacteria in the mouths of intensive care patients. All three protocols include cleaning the mouth with a toothbrush or sponge and fluoride toothpaste. One protocol uses this cleaning alone, one adds chlorhexidine, and one adds hexetidine. Chlorhexidine and hexetidine are antiseptics used to reduce microorganisms in the mouth. Trained nursing staff provide oral care twice daily.
Read more
Saliva samples are collected before the first study oral care procedure, within 24 hours of intensive care admission, and again on the third day. The samples are examined to identify and count selected bacteria and yeasts. Bacteria are also tested for resistance to antibiotics.
The study also examines whether antibiotic use, previous hospital stays, the type of breathing support, and oral hygiene at admission are associated with the presence of these microorganisms. The findings may help improve oral care protocols for intensive care patients.
Read the detailed description
This single-center comparative interventional study evaluates the effects of three oral hygiene protocols on oral colonization by Gram-negative bacteria in patients admitted to the medical intensive care unit of Sestre milosrdnice University Hospital Center, Zagreb, Croatia.
The study includes patients admitted with pneumonia, exacerbation of chronic obstructive pulmonary disease, pulmonary embolism, or cardiac decompensation. Patients receiving and not receiving antibiotic therapy are included, as are patients breathing spontaneously or receiving noninvasive or invasive mechanical ventilation.
Before the intervention begins, an oral examination is performed to assess visible dental plaque and identify oral mucosal lesions. Nursing staff receive standardized training in the oral care procedures to promote consistent delivery of the interventions. Oral hygiene is performed twice daily for three minutes using suction toothbrushes or sponges, according to the patient's dentition, and fluoride toothpaste without sodium lauryl sulfate. The three protocols comprise mechanical cleaning alone, mechanical cleaning with the addition of 0.2% chlorhexidine, and mechanical cleaning with the addition of hexetidine.
Unstimulated saliva is collected within the first 24 hours after intensive care admission, before the first oral hygiene procedure, and again on day 3 before oral care. Samples are cultured to identify and quantify selected Gram-negative bacteria, including Klebsiella pneumoniae, Escherichia coli, Citrobacter species, Proteus species, Enterobacter species, Serratia species, Acinetobacter baumannii complex, and Pseudomonas aeruginosa. Candida species are also assessed. Microbial counts are expressed as colony-forming units per milliliter of saliva. Antimicrobial susceptibility testing is performed on recovered bacterial isolates, with additional investigation of carbapenem resistance where indicated.
The analysis compares changes in microbial colonization within and between the oral hygiene groups. It also examines associations with recent hospitalization, antibiotic use during the preceding three months, antibiotic treatment at admission, baseline oral hygiene, and the type of respiratory support. The study aims to inform the standardization of oral hygiene procedures and the selection of antiseptics for intensive care patients.
Participants were assigned consecutively to the three oral hygiene protocols according to a predefined repeating sequence (Protocol 1, Protocol 2, Protocol 3). No random allocation sequence or allocation concealment was used.
- Conditions
- Oral Bacterial Colonization, Oral Hygiene
- Being tested
- Mechanical Oral Hygiene, Chlorhexidine, Hexetidine
- Keywords
- Intensive Care Unit, Oral Care, Oral Hygiene Protocols, Gram-Negative Bacteria, Oral Microbiota, Salivary Microbiology, Chlorhexidine, Hexetidine, Toothbrushing, Antimicrobial Resistance, Candida, Critical Illness
- Medical subject headings
- Torulopsis, Critical Illness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mechanical Oral HygieneProcedure or surgery
Oral cleaning with a suction toothbrush or sponge, according to the participant's dentition, and fluoride toothpaste without sodium lauryl sulfate. Oral care is performed by trained nursing staff twice daily for three minutes.
ChlorhexidineDrug
Application of 0.2% chlorhexidine to the oral cavity using sterile gauze and a spatula after mechanical cleaning, twice daily.
HexetidineDrug
Application of hexetidine to the oral cavity using sterile gauze and a spatula after mechanical cleaning, twice daily.
| Study group | Role | What they receive |
|---|---|---|
| Mechanical Oral Hygiene Alone | Active comparator | Participants receive oral cleaning with a suction toothbrush or sponge, according to their dentition, and fluoride toothpaste without sodium lauryl sulfate. Trained nursing staff perform oral care twice daily for three minutes. No additional antiseptic is used. Receives: Procedure: Mechanical Oral Hygiene |
| Mechanical Oral Hygiene With Chlorhexidine | Experimental | Participants receive oral cleaning with a suction toothbrush or sponge, according to their dentition, and fluoride toothpaste without sodium lauryl sulfate, followed by application of 0.2% chlorhexidine using sterile gauze and a spatula. Trained nursing staff perform oral care twice daily for three minutes. Receives: Procedure: Mechanical Oral Hygiene; Drug: Chlorhexidine |
| Mechanical Oral Hygiene With Hexetidine | Experimental | Participants receive oral cleaning with a suction toothbrush or sponge, according to their dentition, and fluoride toothpaste without sodium lauryl sulfate, followed by application of hexetidine using sterile gauze and a spatula. Trained nursing staff perform oral care twice daily for three minutes. Receives: Procedure: Mechanical Oral Hygiene; Drug: Hexetidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Salivary Gram-Negative Bacterial Counts From Baseline to Day 3
Change in the concentration of culturable Gram-negative bacteria in unstimulated saliva from baseline to day 3, compared among the three oral hygiene groups. Bacterial counts are expressed as colony-forming units per milliliter (CFU/mL), determined by quantitative culture on MacConkey agar. Assessed organisms include Klebsiella pneumoniae, Escherichia coli, Citrobacter species, Proteus species, Enterobacter species, Serratia species, Acinetobacter baumannii complex, and Pseudomonas aeruginosa. Baseline saliva is collected within 24 hours of intensive care admission, before the first study oral hygiene procedure. The day 3 sample is collected before oral hygiene.
Measured: Baseline (within 24 hours of intensive care admission) and day 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2026
- Study start1 Jun 2026
- Primary completion1 Sep 2026
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Oral Bacterial ColonizationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- This single-center study uses a parallel-group design with three oral hygiene protocols. Participants are assigned consecutively according to a predefined repeating sequence (Protocol 1, Protocol 2, Protocol 3). Each participant receives the assigned protocol throughout the study. The protocols comprise mechanical cleaning with fluoride toothpaste alone, the same cleaning with chlorhexidine, or the same cleaning with hexetidine.
- Masking
- None (open label)
- Enrolment
- 86 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Zagreb
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Bruno Špiljak, University of Zagreb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07868549
- Sponsor's protocol ID
- 05-PA-15-5/2017
- Status last verified
- Oct 2026
- First submitted
- 5 Oct 2026
- Last updated
- 9 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: There is currently no plan to share individual participant data with other researchers. Study findings will be disseminated through scientific publications presenting aggregate results.
Publications
Aoun G, Saadeh M, Berberi A. Effectiveness of Hexetidine 0.1% Compared to Chlorhexidine Digluconate 0.12% in Eliminating Candida Albicans Colonizing Dentures: A Randomized Clinical In Vivo Study. J Int Oral Health. 2015 Aug;7(8):5-8.
PubMed 26464531Alhazzani W, Smith O, Muscedere J, Medd J, Cook D. Toothbrushing for critically ill mechanically ventilated patients: a systematic review and meta-analysis of randomized trials evaluating ventilator-associated pneumonia. Crit Care Med. 2013 Feb;41(2):646-55. doi: 10.1097/CCM.0b013e3182742d45.
PubMed 23263588Hua F, Xie H, Worthington HV, Furness S, Zhang Q, Li C. Oral hygiene care for critically ill patients to prevent ventilator-associated pneumonia. Cochrane Database Syst Rev. 2016 Oct 25;10(10):CD008367. doi: 10.1002/14651858.CD008367.pub3.
PubMed 27778318
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of the Effect of Three Oral Hygiene Protocols on Gram-Negative Microbiota in Patients Treated in an Intensive Care Unit
- ClinicalTrials.gov ID
- NCT07868549
- Acronym / sponsor ID
- 05-PA-15-5/2017
- Conditions
- Oral Bacterial Colonization, Oral Hygiene
- Keywords
- Intensive Care Unit, Oral Care, Oral Hygiene Protocols, Gram-Negative Bacteria, Oral Microbiota, Salivary Microbiology, Chlorhexidine, Hexetidine
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 86 participants (estimated)
- Lead sponsor
- University of ZagrebUniversity, hospital or other
- Study start
- 1 Jun 2026 (actual)
- Primary completion
- 1 Sep 2026 (actual)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 9 Oct 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Patients in intensive care may develop changes in the bacteria found in their mouths. Some of these bacteria can cause infections, and patients who cannot clean their own teeth depend on staff to provide oral care.
This study compares three oral hygiene protocols to assess their effects on potentially harmful bacteria in the mouths of intensive care patients. All three protocols include cleaning the mouth with a toothbrush or sponge and fluoride toothpaste. One protocol uses this cleaning alone, one adds chlorhexidine, and one adds hexetidine. Chlorhexidine and hexetidine are antiseptics used to reduce microorganisms in the mouth. Trained nursing staff provide oral care twice daily.
Saliva samples are collected before the first study oral care procedure, within 24 hours of intensive care admission, and again on the third day. The samples are examined to identify and count selected bacteria and yeasts. Bacteria are also tested for resistance to antibiotics.
The study also examines whether antibiotic use, previous hospital stays, the type of breathing support, and oral hygiene at admission are associated with the presence of these microorganisms. The findings may help improve oral care protocols for intensive care patients.
Detailed description
This single-center comparative interventional study evaluates the effects of three oral hygiene protocols on oral colonization by Gram-negative bacteria in patients admitted to the medical intensive care unit of Sestre milosrdnice University Hospital Center, Zagreb, Croatia.
The study includes patients admitted with pneumonia, exacerbation of chronic obstructive pulmonary disease, pulmonary embolism, or cardiac decompensation. Patients receiving and not receiving antibiotic therapy are included, as are patients breathing spontaneously or receiving noninvasive or invasive mechanical ventilation.
Before the intervention begins, an oral examination is performed to assess visible dental plaque and identify oral mucosal lesions. Nursing staff receive standardized training in the oral care procedures to promote consistent delivery of the interventions. Oral hygiene is performed twice daily for three minutes using suction toothbrushes or sponges, according to the patient's dentition, and fluoride toothpaste without sodium lauryl sulfate. The three protocols comprise mechanical cleaning alone, mechanical cleaning with the addition of 0.2% chlorhexidine, and mechanical cleaning with the addition of hexetidine.
Unstimulated saliva is collected within the first 24 hours after intensive care admission, before the first oral hygiene procedure, and again on day 3 before oral care. Samples are cultured to identify and quantify selected Gram-negative bacteria, including Klebsiella pneumoniae, Escherichia coli, Citrobacter species, Proteus species, Enterobacter species, Serratia species, Acinetobacter baumannii complex, and Pseudomonas aeruginosa. Candida species are also assessed. Microbial counts are expressed as colony-forming units per milliliter of saliva. Antimicrobial susceptibility testing is performed on recovered bacterial isolates, with additional investigation of carbapenem resistance where indicated.
The analysis compares changes in microbial colonization within and between the oral hygiene groups. It also examines associations with recent hospitalization, antibiotic use during the preceding three months, antibiotic treatment at admission, baseline oral hygiene, and the type of respiratory support. The study aims to inform the standardization of oral hygiene procedures and the selection of antiseptics for intensive care patients.
Participants were assigned consecutively to the three oral hygiene protocols according to a predefined repeating sequence (Protocol 1, Protocol 2, Protocol 3). No random allocation sequence or allocation concealment was used.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- This single-center study uses a parallel-group design with three oral hygiene protocols. Participants are assigned consecutively according to a predefined repeating sequence (Protocol 1, Protocol 2, Protocol 3). Each participant receives the assigned protocol throughout the study. The protocols comprise mechanical cleaning with fluoride toothpaste alone, the same cleaning with chlorhexidine, or the same cleaning with hexetidine.
| Arm | Type | Receives |
|---|---|---|
| Mechanical Oral Hygiene Alone | Active comparator | Procedure: Mechanical Oral HygieneParticipants receive oral cleaning with a suction toothbrush or sponge, according to their dentition, and fluoride toothpaste without sodium lauryl sulfate. Trained nursing staff perform oral care twice daily for three minutes. No additional antiseptic is used. |
| Mechanical Oral Hygiene With Chlorhexidine | Experimental | Procedure: Mechanical Oral Hygiene, Drug: ChlorhexidineParticipants receive oral cleaning with a suction toothbrush or sponge, according to their dentition, and fluoride toothpaste without sodium lauryl sulfate, followed by application of 0.2% chlorhexidine using sterile gauze and a spatula. Trained nursing staff perform oral care twice daily for three minutes. |
| Mechanical Oral Hygiene With Hexetidine | Experimental | Procedure: Mechanical Oral Hygiene, Drug: HexetidineParticipants receive oral cleaning with a suction toothbrush or sponge, according to their dentition, and fluoride toothpaste without sodium lauryl sulfate, followed by application of hexetidine using sterile gauze and a spatula. Trained nursing staff perform oral care twice daily for three minutes. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Admission to the medical intensive care unit of Sestre milosrdnice University Hospital Center, Zagreb, Croatia, for pneumonia, exacerbation of chronic obstructive pulmonary disease, pulmonary embolism, or cardiac decompensation.
- Expected survival longer than 72 hours.
- Written informed consent provided by the patient or an authorized representative.
- Patients of either sex are eligible, regardless of age. Patients receiving or not receiving antibiotic therapy may participate. Patients breathing spontaneously or receiving noninvasive or invasive mechanical ventilation are eligible.
Key exclusion criteria (4 listed)
- Allergy to chlorhexidine or hexetidine.
- Treatment with immunosuppressive agents or corticosteroids.
- Previous radiotherapy to the head and neck region.
- Presence of oral mucosal lesions at the baseline examination.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mechanical Oral HygieneOral cleaning with a suction toothbrush or sponge, according to the participant's dentition, and fluoride toothpaste without sodium lauryl sulfate. Oral care is performed by trained nursing staff twice daily for three minutes. | Procedure or surgery | Mechanical Oral Hygiene Alone, Mechanical Oral Hygiene With Chlorhexidine, Mechanical Oral Hygiene With Hexetidine |
| ChlorhexidineApplication of 0.2% chlorhexidine to the oral cavity using sterile gauze and a spatula after mechanical cleaning, twice daily. | Drug | Mechanical Oral Hygiene With Chlorhexidine |
| HexetidineApplication of hexetidine to the oral cavity using sterile gauze and a spatula after mechanical cleaning, twice daily. | Drug | Mechanical Oral Hygiene With Hexetidine |
Primary outcome
Change in Salivary Gram-Negative Bacterial Counts From Baseline to Day 3
Time frame: Baseline (within 24 hours of intensive care admission) and day 3
Change in the concentration of culturable Gram-negative bacteria in unstimulated saliva from baseline to day 3, compared among the three oral hygiene groups. Bacterial counts are expressed as colony-forming units per milliliter (CFU/mL), determined by quantitative culture on MacConkey agar. Assessed organisms include Klebsiella pneumoniae, Escherichia coli, Citrobacter species, Proteus species, Enterobacter species, Serratia species, Acinetobacter baumannii complex, and Pseudomonas aeruginosa. Baseline saliva is collected within 24 hours of intensive care admission, before the first study oral hygiene procedure. The day 3 sample is collected before oral hygiene.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2026.
- Background: PubMed 26464531Aoun G, Saadeh M, Berberi A. Effectiveness of Hexetidine 0.1% Compared to Chlorhexidine Digluconate 0.12% in Eliminating Candida Albicans Colonizing Dentures: A Randomized Clinical In Vivo Study. J Int Oral Health. 2015 Aug;7(8):5-8.
- Background: PubMed 23263588Alhazzani W, Smith O, Muscedere J, Medd J, Cook D. Toothbrushing for critically ill mechanically ventilated patients: a systematic review and meta-analysis of randomized trials evaluating ventilator-associated pneumonia. Crit Care Med. 2013 Feb;41(2):646-55. doi: 10.1097/CCM.0b013e3182742d45.
- Background: PubMed 27778318Hua F, Xie H, Worthington HV, Furness S, Zhang Q, Li C. Oral hygiene care for critically ill patients to prevent ventilator-associated pneumonia. Cochrane Database Syst Rev. 2016 Oct 25;10(10):CD008367. doi: 10.1002/14651858.CD008367.pub3.
- Individual participant dataSharing planned: No. There is currently no plan to share individual participant data with other researchers. Study findings will be disseminated through scientific publications presenting aggregate results.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Mechanical Oral Hygiene, Chlorhexidine and Hexetidine in people with Oral Bacterial Colonization and Oral Hygiene, run by University of Zagreb at 1 site in Croatia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: enrolling by invitation, as of the sponsor's last update on 9 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Croatia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Salivary Gram-Negative Bacterial Counts From Baseline to Day 3 (time frame: Baseline (within 24 hours of intensive care admission) and day 3). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07868549, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Oct 2026; AzTrials last refreshed its copy on 7 Nov 2026.