Evaluation of chlorhexidine mouthwash for oropharyngeal decontamination in patients with COVID-19
| ISRCTN | ISRCTN12877496 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN12877496 |
| Sponsor | Health Research Institute of the Balearic Islands |
| Funder | Investigator initiated and funded |
- Submission date
- 06/09/2026
- Registration date
- 22/09/2026
- Last edited
- 22/09/2026
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English summary of protocol
Background and study aims
When the COVID-19 pandemic began, the virus that causes it (SARS-CoV-2) was known to be present in large amounts in the mouth and throat. Laboratory experiments showed that some antiseptic mouthwashes can kill the virus in a test tube. This raised a question that mattered in everyday hospital practice: if patients admitted with COVID-19 rinsed their mouth with an antiseptic, would the amount of virus in their throat fall faster, and would they get better sooner? Chlorhexidine is one of the most widely used mouthwashes in hospitals, so this study set out to test whether rinsing with chlorhexidine reduces the amount of SARS-CoV-2 in the throat of patients admitted to hospital with COVID-19 that was not severe.
Who can participate?
Adults admitted to hospital (the approved protocol specified 18 to 60 years; in practice participants aged up to 75 were enrolled) with a positive SARS-CoV-2 PCR test whose COVID-19 was not severe, and who were able to rinse their mouth properly for 30 seconds.
What does the study involve?
Participants were allocated at random, by chance, to one of three groups. The first group rinsed with chlorhexidine 0.12%. The second group rinsed with chlorhexidine 0.12% that also contained 5% alcohol, prepared by the hospital pharmacy. The third group was a comparison group and did not use any mouthwash. Those in the two mouthwash groups rinsed with 15 mL for at least 30 seconds, three times a day for 7 days, after meals and after brushing their teeth, and then had nothing to eat or drink for at least an hour. Everyone in all three groups received the usual hospital treatment for COVID-19. A swab from the nose and throat was taken before the first rinse, and throat swabs were taken again after 48 hours and after 7 days, to measure how much virus was present. Participants were seen every day until they went home or until day 7.
What are the possible benefits and risks of participating?
The possible benefit was a faster fall in the amount of virus in the throat, which might have shortened the illness. Chlorhexidine mouthwash is widely used and generally well tolerated; the known effects are usually mild and include an altered sense of taste, a temporary burning sensation in the mouth, and staining of the teeth with prolonged use. No serious effects were expected over a 7-day course, and none attributable to the mouthwashes were recorded.
Where is the study run from?
Hospital Universitari Son Espases, Palma, Illes Balears, Spain.
When is the study starting and how long is it expected to run for?
Participants were recruited from April 2020 to March 2021.
Who is funding the study?
This study received no funding
Who is the main contact?
Dr. Antoni Campins, antonia.campins@ssib.es
Dr. Francisco Fanjul, franciscoj,fanjul@ssib.es
Unidad de Enfermedades infecciosas, Servicio de Medicina Interna, Hospital Son Espases,
Carretera de Valldemossa 79, 07120, Palma, España
What were the results?
Rinsing with chlorhexidine did not make the virus clear from the throat any faster. There was a small reduction in the amount of virus in the chlorhexidine groups after 48 hours, but it was at the edge of what would be considered a real difference, and it had disappeared completely by day 7. The proportion of patients whose PCR test became negative was no higher in the chlorhexidine groups, and there was no difference between the groups in the need for oxygen, admission to intensive care, or length of hospital stay. No patient died. What most influenced how quickly the virus cleared was how much virus a patient had at the start, not whether they used a mouthwash.
Contact information
Principal investigator
Carretera Valldemossa 79
Palma de Mallorca
07120
Spain
| Phone | +34 871205000 |
|---|---|
| antonia.campins@ssib.es |
Public, Scientific
Carretera Valldemossa 79
Palma de Mallorca
07120
Spain
 ORCID ID |
0000-0003-1852-0330 |
|---|---|
| Phone | +34 871205000 |
| franciscoj.fanjul@ssib.es |
Study information
| Primary study design | Interventional |
|---|---|
| Allocation | Randomized controlled trial |
| Masking | Open (masking not used) |
| Control | Active |
| Assignment | Parallel |
| Purpose | Treatment |
| Scientific title | Antiviral effect of oral decontamination with alcoholic chlorhexidine in SARS-CoV-2 respiratory infection |
| Study objectives | |
| Ethics approval(s) |
Approved 19/04/2020, Comité de Ética de la Investigación de las Islas Baleares (C. de Jesús, 38 A, Palma, 07010, Spain; +34 971 17 73 78; ceic_ib@caib.es), ref: CEI-IB 4199-20PI |
| Health condition(s) or problem(s) studied | COVID-19 (SARS-CoV-2 infection), non-severe, in hospitalised adults |
| Intervention | Group 1 (aqueous CHX): chlorhexidine digluconate 0.12% mouthwash (Clorhexidina Lacer, 15 mL single-dose sachet), 15 mL rinsed for at least 30 seconds, three times daily, after main meals and toothbrushing, with no food or drink for at least 60 minutes afterwards, for 7 days, in addition to standard care. Group 2 (alcoholic CHX): chlorhexidine digluconate 0.12% plus ethanol 5%, compounded by the Hospital Pharmacy Service (pharmacotechnics laboratory), same dose, frequency, technique and duration, in addition to standard care. Control: standard care only, no mouthwash. Standard care in all arms followed the Spanish Ministry of Health and local hospital protocols in force, and could include lopinavir/ritonavir, azithromycin, hydroxychloroquine, remdesivir, corticosteroids, oxygen therapy, intubation and mechanical ventilation, antibiotics and vasoactive support as indicated. Randomisation was performed using a random sequence generated with an online tool. |
| Intervention type | Drug |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | marketed antiseptic, non-medicinal-product intervention |
| Primary outcome measure(s) |
|
| Key secondary outcome measure(s) |
|
| Completion date | 15/03/2021 |
Eligibility
| Participant type(s) | |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 60 Years |
| Sex | All |
| Target sample size at registration | 110 |
| Total final enrolment | 107 |
| Key inclusion criteria | 1. Hospitalised adults aged 18–60 years 2. PCR-confirmed SARS-CoV-2 infection 3. Non-severe COVID-19 (NEWS score ≤6) 4. Able to understand and correctly perform a 30-second mouth rinse 5. Written informed consent |
| Key exclusion criteria | 1. NEWS score >7 at randomisation 2. Contraindication or allergy to mouthwash components 3. Respiratory rate >30 breaths/min on room air 4. Baseline oxygen saturation <92% 5. PaO2/FiO2 <250 6. Any clinical situation precluding safe performance of rinses in the judgement of the responsible physician (e.g. cognitive impairment, advanced age) |
| Date of first enrolment | 23/04/2020 |
| Date of final enrolment | 08/03/2021 |
Locations
Countries of recruitment
- Spain
Study participating centres
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|
Editorial Notes
22/09/2026: Trial's existence confirmed by Comité de Ética de la Investigación de las Islas Baleares.
