Mouthwashes for Gingivitis: Comparing a Hydrogen Peroxide-Hyaluronic Acid Mix, Hyaluronic Acid, and Chlorhexidine, A Triple-Blind Clinical Trial (TRIPLE-G)

Ramziyah Hayder Bakr

Status: Not yet enrolling

Conditions: Plaque Induced Gingival Disease

Treatments: Combination Product: 2- Hyaluronic acid; Combination Product: Chlorhexidine; Combination Product: 1-Hydrogen peroxide and hyaluronic acid; Combination Product: Placebo mouthwash

Study type: Interventional

Funder types: Other

Identifiers

NCT07031388

RP-DPH-KHCMS-2025-001

Details and patient eligibility

About

This randomized, triple-blind clinical trial is designed to evaluate the efficacy of four different mouthwash formulations - hydrogen peroxide with hyaluronic acid, hyaluronic acid alone, chlorhexidine, and placebo - in four parallel arms. The study will take place at multiple centers, starting on June 1, 2025, and is expected to conclude by October 1, 2026. There is no external funding source for this study.

Eligible participants include systemically healthy individuals aged 18 to 35 years with a gingival and plaque index score of 1 or higher. Individuals with systemic or oral diseases will be excluded. Participants will be randomly assigned to one of four groups, each receiving a different mouthwash formulation for twice-daily use, following standardized oral hygiene instructions.

The potential benefit includes a reduced risk of gingivitis progression to periodontitis. There are no significant anticipated risks, though mild oral discomfort or taste alteration may occur.

Full description

This randomized, triple-blind clinical trial aims to compare the effectiveness and safety of four different mouthwash formulations in managing gingivitis. The test group will use a mouthwash containing hydrogen peroxide (H2O2 1.80% )and hyaluronic acid (HA 0.10%). The three comparator groups will receive either chlorhexidine (CHX 0.12%), hyaluronic acid (HA 0.12%) (high molecular weight) alone, or a placebo mouthwash.

A total of four parallel arms will be used. Participants will be randomly assigned using a computer-generated randomization list. Blinding will apply to participants, clinical evaluators, and data analysts to maintain objectivity (triple-blind design).

Each participant will use the assigned mouthwash twice daily for three weeks, following standard oral hygiene instructions.

The primary outcomes will be changes in gingival inflammation, plaque accumulation, and bleeding on probing, assessed using the Gingival Index (GI), Plaque Index (PI), and Bleeding on Probing (BOP). Measurements will be taken at baseline, and after one, two, and three weeks of intervention.

The secondary outcomes will include reported side effects such as taste alteration, tooth discoloration, and overall comfort using the mouthwash.

The study is designed to determine which formulation offers the best balance of clinical effectiveness and patient acceptability in gingivitis management.

Enrollment: 80 estimated patients

Sex: All

Ages: 18 to 35 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Subjects with a gingival index score of 1 or greater.
• Subjects with a plaque index score of 1 or greater
• Systemically healthy individuals.
• Minimum of 20 natural teeth

Exclusion criteria

• Current use of any mouthwash.
• Smoking habit.
• Presence of active caries.
• Overhanged restorations and crowns.
• Presence of supra or subgingival calculus.
• Ongoing orthodontic treatment (including post-treatment retainer)
• Periodontal treatment within the past 6 months and a diagnosis of periodontitis.
• Use of antibiotics within the past 4 months or requirement for antibiotic prophylaxis.
• Systematic or topical non-steroidal anti-inflammatory drug treatment for the past 4 months
• Pregnancy or lactation.
• History of heart valve replacement.
• Known intolerance or allergy to mouth rinses.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

80 participants in 4 patient groups, including a placebo group

1- Arm 1 Hydrogen peroxide + Hyaluronic acid

Experimental group

Description:

Participants in this arm will receive a mouthwash formulation containing 1.8% hydrogen peroxide and 0.10% hyaluronic acid. The mouthwash is to be used twice daily for 3 weeks, following standardized oral hygiene instructions. This combination is intended to synergize the antimicrobial effects of hydrogen peroxide with the anti-inflammatory and healing properties of hyaluronic acid to manage gingivitis.

Treatment:

Combination Product: 1-Hydrogen peroxide and hyaluronic acid

2- Arm 2 Hyaluronic acid alone

Experimental group

Description:

Participants in this arm will use a mouthwash containing 0.12% high molecular weight hyaluronic acid only. The mouthwash will be used twice daily for 3 weeks. Hyaluronic acid is known for its anti-inflammatory, tissue repair, and moisturizing effects, and this arm will assess its standalone effectiveness in improving gingival health in patients with gingivitis.

Treatment:

Combination Product: 2- Hyaluronic acid

3- Arm 3 chlorhexidine (CHX)

Experimental group

Description:

Participants in this arm will receive a commercially available mouthwash containing 0.12% chlorhexidine gluconate. The solution will be used twice daily for 3 weeks, following standardized oral hygiene instructions. Chlorhexidine is a widely used antiseptic known for its broad-spectrum antimicrobial activity and effectiveness in reducing plaque and gingival inflammation.

Treatment:

Combination Product: Chlorhexidine

4- Arm 4 placebo

Placebo Comparator group

Description:

Participants in this arm will receive a placebo mouthwash designed to closely mimic the active treatments in appearance, taste, and viscosity, ensuring effective blinding. The formulation comprises: * 2 ml glycerin * Vanilla flavoring agent * Brown food coloring * Distilled water to make up 1 liter This placebo was prepared at Awamedica, a certified Class A pharmaceutical manufacturer known for its state-of-the-art formulation laboratory and commitment to quality in pharmaceutical manufacturing. The solution is dispensed in 120 ml opaque brown bottles, each labeled solely with the participant's number to maintain blinding. Participants are instructed to use the mouthwash twice daily for 3 weeks, following standardized oral hygiene instructions. This arm serves as a negative control to assess the true efficacy of the active mouthwash formulations in managing gingivitis.

Treatment:

Combination Product: Placebo mouthwash