Assessing the Efficacy of a Carbamide Peroxide Mouthwash for Oral Wound Healing, Oral Hygiene and Xerostomia Relief

Not Applicable

Completed

• Conditions: Mouth Dryness; Wound Heal; Oral Dryness; Postoperative Pain; Biopsy Wound; Mouth; Wound; Sjogren's Syndrome; Dental Plaque; Gingival Inflammation
• Interventions: Device: Placebo mouthwash; Device: Carbamide Peroxide Mouthwash

• Registration Number: NCT06363955
• Lead Sponsor: National and Kapodistrian University of Athens

Brief Summary

The aim of this study is to evaluate the efficacy and safety of a carbamide peroxide mouthwash regarding oral wound healing, postoperative symptoms, xerostomia (dry mouth) and oral hygiene improvement. Study participants have reported dry mouth and are scheduled for a diagnostic biopsy of minor labial salivary glands to investigate Sjögren's Syndrome, following consultation with their rheumatologist. This is a standardized diagnostic procedure that leads to healing by primary intention (i.e. wound edges are closely re-approximated with sutures).

Researchers are comparing this mouthwash with a placebo (a look-and-taste-alike substance that contains no active ingredients) to see if it is helpful with healing of wounds in the mouth and associated symptoms, improving dry mouth and/or oral hygiene. Carbamide peroxide breaks down to hydrogen peroxide and urea and shows antiseptic and antimicrobial properties and it might help with the parameters to be assessed. Participants randomly get the carbamide peroxide mouthwash or the placebo one to use for 14 days after the biopsy. The investigators will not know which one they are providing as the bottles will be identical.

Oral wound healing, postoperative symptoms (such as pain, eating and speech difficulties), oral hygiene (dental plaque and gingival inflammation), improvement of dry mouth and quality of life are assessed during a 14-day period after the biopsy. Participants are required to visit the clinic three times, one for the initial consultation and the biopsy, one at 7 days and one at 14 days after the biopsy. They are asked to fill in some questionnaires, while certain procedures (such as measuring saliva) and assessments (like evaluating the dental plaque and gingival inflammation) take place. During the first week they, also, keep a diary of their symptoms, as instructed.

Detailed Description

This is a prospective, randomized, triple-blind, placebo-controlled clinical trial and post-market clinical follow-up (PMCF) study, expected to last approximately 12 months. All procedures/visits/examinations are taking place in the Oral Medicine and Pathology Clinic at the School of Dentistry, National and Kapodistrian University of Athens, Greece. Participants with reported dry mouth are scheduled for a diagnostic biopsy of minor labial salivary glands to investigate Sjögren's Syndrome, following consultation with their rheumatologist. This is a standardized diagnostic procedure that leads to healing by primary intention. After checking if they comply with the study's criteria, they are informed about the study and the biopsy procedure (including possible complications) and they sign the Ιnformed Consent Form.

All biopsies are obtained from the lower lip with a 12 - 15 mm linear incision. After blunt dissection of the borders, 5-7 lobules of minor salivary glands are removed by dissection with the scalpel or a curved mosquito forceps and the use of tweezers. Attention is paid not to injure nerve branches or vessels. Adequate hemostasis is achieved by manual pressure, and the incision is closed by simple interrupted non-absorbable 4/0 silk sutures at equal distances. Participants are instructed to have cold, soft diet for the day and use ice packs externally for 1-2 hours after the procedure. Use of 500mg paracetamol up to 3 times is permitted for day 0. Following their normal oral hygiene routine (brushing and toothpaste) is suggested.

Subsequently, they are assigned randomly in a 1:1 ratio to receive either a carbamide peroxide mouthwash or a placebo comparator, i.e. a look-alike substance that lacks active ingredients. Both participants and investigators are masked. Follow-up examinations are conducted at 7 and 14 days. On day 7 the sutures are cut.

The evaluation includes:

• oral wound healing (primary intention) assessed by scores (primary outcome)

and secondarily:

* oral wound healing via measuring the incision/wound length

* postoperative symptoms (such as pain, eating and speech difficulties)

* quality of life assessed by a questionnaire

* improvement of dry mouth through subjective and objective measurements

* oral hygiene via plaque and gingival indices.

All data are anonymized and the outcome assessors are masked.

The mouthwash used in the experinmental/test group is a Class IIa, CE-marked (Conformité Européenne) medical device. This mouthwash contains hydrogen carbamide that breaks down to hydrogen peroxide and urea. Hydrogen peroxide has antiseptic and antimicrobial properties, as well the ability to mechanically clean affected areas by producing an oxygenated foam, while urea shares antiseptic and antimicrobial abilities as well and can enhance the pH of the oral cavity. These substances have been used in wound healing either in skin or intraorally, as well as in oral hygiene for a long time. However, to date, no clinical trial examining the use of a hydrogen carbamide/peroxide product in oral wound healing, postoperative symptoms or dry mouth has been reported. Published clinical studies on the control of dental plaque and periodontal inflammation exhibit partially conflicting results.

Study Timeline

• Study Start: 2023-04-25
• Primary Completion: 2024-04-01
• Study Completion: 2024-04-01
• Study First Submitted: 2024-04-05
• Study First Submitted QC: 2024-04-10
• Study First Posted: 2024-04-12
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-01
• Last Update Posted: 2024-07-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 54

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo mouthwash	A mouthwash that looks, smells and tastes like the experinmental mouthwash without active ingredients
Carbamide Peroxide Mouthwash	Carbamide Peroxide Mouthwash	A mouthwash containing carbamide proxide/hydrogen peroxide as active ingredient

Primary Outcome Measures

Name	Time	Method
Assessment of wound healing based on the modified Landry Healing Index on day 14	Day 14	Healing will be measured clinically using specific scores. The modified Landry Healing Index consists of the assessment of 5 clinical parameters (tissue color, bleeding on palpation, presence of granulation tissue, presence of suppuration, and healing of the surgical margin). As the initial index referred to gingival healing, it was slightly modified as in other studies, so that it refers to oral mucosal healing. The index values range from 1 to 5, where 1 corresponds to "very poor healing" and 5 to "excellent healing". Comparisons will be made between the carbamide peroxide mouthwash versus the placebo group.
Assessment of wound healing based on a modified version of the Early Wound Healing Score (EHS) on day 14	Day 14	Healing will be measured clinically using specific scores. The EHS is composed of 3 parameters: clinical signs of re-epithelization (CSR), clinical signs of haemostasis (CSH), and clinical signs of inflammation (CSI). Zero, 3, 4 or 6 points are used to evaluate CSR (modified by adding point 4), whereas 0, 1, or 2 points are used for CSH and CSI. The EHS is generated by the summation of the points of these 3 parameters. The EHS for ideal wound healing is 10 points, while the worst possible score is 0 points. Comparisons will be made between the carbamide peroxide mouthwash versus the placebo group.
Assessment of wound healing based on the modified Landry Healing Index on day 7	Day 7	Healing will be measured clinically using specific scores. The modified Landry Healing Index consists of the assessment of 5 clinical parameters (tissue color, bleeding on palpation, presence of granulation tissue, presence of suppuration, and healing of the surgical margin). As the initial index referred to gingival healing, it was slightly modified as in other studies, so that it refers to oral mucosal healing. The index values range from 1 to 5, where 1 corresponds to "very poor healing" and 5 to "excellent healing". Comparisons will be made between the carbamide peroxide mouthwash versus the placebo group.
Assessment of wound healing based on a modified version of the Early Wound Healing Score (EHS) on day 7	Day 7	Healing will be measured clinically using specific scores. The EHS is composed of 3 parameters: clinical signs of re-epithelization (CSR), clinical signs of haemostasis (CSH), and clinical signs of inflammation (CSI). Zero, 3, 4 or 6 points are used to evaluate CSR (modified by adding point 4), whereas 0, 1, or 2 points are used for CSH and CSI. The EHS is generated by the summation of the points of these 3 parameters. The EHS for ideal wound healing is 10 points, while the worst possible score is 0 points. Comparisons will be made between the carbamide peroxide mouthwash versus the placebo group.

Secondary Outcome Measures

Name	Time	Method
Postoperative symptoms (pain, eating and speech difficulty) on day 14	Day 14	During the visit in day 14, participants will be asked to record: the greatest intensity of the postoperative pain, as perceived (Numerical and Visual Scale, 0-10), difficulty in eating (Yes/No), difficulty in speaking (Yes/No) and whether any analgesic treatment has been necessary (No or Yes: Which one?). Comparisons will be made between the two groups.
Wound healing based on the incision/wound length	Days 0, 7 and 14	The incision/wound length will be measured in milimeters (mm) during every visit using a UNC 15 (North Carolina) periodontal probe. Standardized pictures will be also taken with an angulation perpendicular to the wound. The same periodontal probe will be placed by the wound as a reference scale. Comparisons will be made between the two groups (mean changes from day 7 to 0, day 14 to 0 and day 14 to 7).
Postoperative symptoms (pain, eating and speech difficulty) during the first week (at home)	Days 0, 1, 2, 3, 4, 5 and 6	Participants will be given a pain diary (PD) to complete at home daily at the end of the day, from day 0 to day 6, with instructions for its completion. Specifically, the participants will record: the greatest intensity of the postoperative pain, as perceived (Numerical and Visual Scale, ranked 0-10), difficulty in eating (Yes/No), difficulty in speaking (Yes/No) and whether any analgesic treatment, apart from the one recommended for day 0, has been necessary (No or Yes: Which one?). Comparisons will be made between the two groups for every day from day 0 to day 6.
Observed (objective) signs of oral dryness	Days 0, 7 and 14	During the clinical exam in each visit, Clinical Oral Dryness Score (CODS) is conducted, which assesses ten key features of dry mouth and allocates one point for each feature. The total score ranges from 0 to 10, with higher scores indicating more severe dry mouth. Comparisons will be made between the two groups on days 7 and 14.
Postoperative symptoms (pain, eating and speech difficulty) on day 7	Day 7	During the visit in day 7, participants will be asked to record: the greatest intensity of the postoperative pain, as perceived (Numerical and Visual Scale, ranked 0-10), difficulty in eating (Yes/No), difficulty in speaking (Yes/No) and whether any analgesic treatment has been necessary (No or Yes: Which one?). Comparisons will be made between the two groups.
Subjective oral dryness symptoms (8-item VAS questionnaire)	Days 0, 7 and 14	During all the visits, patients complete a 8-item 100 mm Visual Analog Scale (VAS) questionnaire developed by Pai et al, 2001 for subjective scoring xerostomia symptoms, namely: difficulty in speaking due to dryness, difficulty in swallowing due to dryness (0 mm: not difficult at all, 100 mm: very difficult), rating the amount of saliva in the mouth (0 mm: a lot, 100 mm: none), level of dryness in the mouth, the throat, the lips and the tongue (0 mm: not dry at all, 100 mm: very dry) and the level of thirst (0 mm: not thirsty at all, 100 mm: very thirsty). Comparisons will be made for each item of the questionnaire between the two groups by calculating the changes from day 7 to 0, day 14 to 0 and day 14 to 7. Higher values of the changes represent a better outcome.
Oral Hygiene - Dental Plaque: Full-Mouth Plaque Index	Days 0, 7 and 14	The Plaque Index (PI) by Silness \& Loe 1964 is a score of 0-3 with higher scores indicating greater plaque accumulation. Every tooth is evaluated with a UNC 15 periodontal probe at 4 sites (mesiobuccal, mid-buccal, distobuccal, and lingual) as 0 = No plaque, 1 = A film of plaque adhering to free gingival margin and adjacent area of tooth, which may be seen by using the probe or disclosing solution, 2 = Moderate accumulation of soft deposits within the gingival pocket, or on the tooth and gingival margin, which can be seen with the naked eye, 3 = Abundance of soft matter within the gingival pocket and/or on the tooth and gingival margin.; The calculation of full mouth index refers to the sum of the measurements on the 4 surfaces of all the teeth examined divided by four and then by the number of teeth examined. The final score ranges from 0-3. Full mouth PI is measured in all visits and comparisons will be made between the two groups on day 7 and 14 (mean changes from baseline).
Change in Unstimulated Saliva Flow Rate	Days 0 and 14	Unstimulated whole saliva is collected in a cap over a 5-minute time period at around the same time of the day on days 0 and 14 and the volume is measured. The Unstimulated Saliva Flow Rate is measured in ml per minute and the change is calculated by subtracting the measurement at day 0 from the measurement at 14 days. Comparisons will be made between the two groups.
Oral Hygiene - Gingival Inflammation: Full Mouth Gingival Index	Days 0, 7 and 14	The Gingival Index (GI) by Loe \& Silness 1963 scores from 0 to 3, with higher scores indicating greater inflammation. The examination is performed by sliding the periodontal probe (UNC 15) on the free gums (modification according to Löe - 1967) on all existing teeth of the person. Every tooth is evaluated at 4 surfaces (mesiobuccal, mid-buccal, distobuccal, and lingual). By dividing the sum of the values by 4, the gingival index of the tooth is calculated. The full mouth gingival index is obtained by summing the indices of each tooth divided by the total number of teeth examined. The overall index score, representing inflammation, is rated as mild (mean 0,1-1,0), moderate (1,1-2,0) and severe (2,1-3). Comparisons of the full mouth GI scores will be made between the 2 groups on day 7 and 14 (mean changes from baseline).
Assessment of swelling in the biopsy area	Day 7 and 14	The existence of swelling in the biopsy area is assessed via a Yes/No question ("Is there swelling in the biopsy area?") during visits on day 7 and 14. Comparisons will be made between the two groups.
Oral Health Related Quality of Life	Day 14	The Oral Health Impact Profile-14 (OHIP-14) scale is used to measure the participants' oral health related quality of life (OHRQoL) after the procedure. It has seven conceptualized domains (two items per domain - 14 total): functional limitation, physical pain, psychological discomfort, physical disability, psychological disability, social disability, and handicap. Participants are asked to rate how frequently they experienced an oral health impact (as described by each item), scoring on a five-point Likert scale: never (score 0), hardly ever (score 1), occasionally (score 2), fairly often (score 3) and very often (score 4). Thus, OHIP-14 scores can range from 0 to 56. A high total value indicates a high negative impact on the OHRQoL. Comparisons will be made between the two groups on day 14.

Trial Locations

Locations (1)

Department of Oral Medicine & Pathology and Hospital Dentistry, School of Dentistry, National and kapodistrian University of Athens; 🇬🇷 Athens, Attiki, Greece