Evaluation of Hyaluronic Acid and Chlorhexidine Gel as an Adjunct to Minimally Invasive Non-surgical Therapy in the Treatment of Stage III and IV Periodontitis: A Randomized Clinical Trial

NCT07731113 | Active Not Recruiting

• 1 other identifier: PER 3-3-1.1
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

Stage III and IV periodontitis are advanced forms of periodontal disease characterized by significant attachment loss, deep periodontal pockets, and progressive destruction of supporting periodontal tissues. Minimally invasive non-surgical therapy (MINST) has been proposed as an effective treatment approach aimed at minimizing tissue trauma while achieving optimal biofilm and calculus removal. Adjunctive therapies may further enhance clinical outcomes by promoting wound healing and reducing inflammation. This randomized clinical trial aims to evaluate the effectiveness of a hyaluronic acid and chlorhexidine gel (Periofix Plus Gel) used as an adjunct to MINST in patients with Stage III and IV periodontitis. Participants will be randomly assigned to receive either MINST alone or MINST combined with local application of the hyaluronic acid/chlorhexidine gel. Clinical periodontal parameters, including probing pocket depth, clinical attachment level, bleeding on probing, and plaque-related indices, will be assessed at baseline and follow-up visits to determine whether adjunctive gel application provides additional clinical benefits compared with MINST alone. The study hypothesis is that the adjunctive use of hyaluronic acid and chlorhexidine gel following MINST will result in greater periodontal pocket reduction, improved clinical attachment gain, and enhanced soft tissue healing compared with MINST alone.

Conditions

Periodontology; Periodontal Disease; Periodontal Diseases; Periodontitis (Stage 3); Gingivitis and Periodontal Diseases; Stage III Periodontitis; Stage IV Periodontitis; Minimally Invasive Non-Surgical Therapy (MINST); Non-Surgical Periodontal Therapy; Hyaluronic Acid; Hyaluronic Acid and Chlorhexidine Gel; Periofix Plus Gel; Adjunctive Periodontal Therapy; Clinical Attachment Level; Probing Pocket Depth; Biofilm Control

Keywords

MINST; Minimally invasive non-surgical technique; Periodontitis treatment; Stage III Periodontitis; Stage IV Periodontitis; Minimally Invasive Non-Surgical Therapy (MINST); Non-Surgical Periodontal Therapy; Hyaluronic Acid; Chlorhexidine; Hyaluronic Acid and Chlorhexidine Gel; Periofix Plus Gel; Adjunctive Periodontal Therapy; Periodontal Pocket; Clinical Attachment Level; Probing Pocket Depth; Periodontal Regeneration; Wound Healing; Biofilm Control; Randomized Clinical Trial; Periodontal Treatment

Outcome Measures

Primary Outcomes (1)

• Probing pocket depth

  Measured from the gingival margin to the bottom of the gingival sulcus. Each tooth will be probed with a light force not exceeding 25 grams at 6 sites

  0, 3, 6 months

Secondary Outcomes (5)

• Clinical attachment level (CAL)

  0, 3, 6 months

• Plaque index

  0, 3, 6 months

• Bleeding on probing

  0, 3, 6 months

• Gingival Marginal Level (GML)

  0, 3, 6 months

• Post-operative Pain

  7 days

Study Arms (2)

Control

ACTIVE COMPARATOR

The control group will receive MINST only for the treatment of deep periodontal pockets. The application of MINST minimizes soft and hard tissue trauma achieving better treatment outcomes in comparison with traditional scaling and root planing. Gingival architecture is maintained, and stability of the area is preserved favoring better clot formation and stabilization

Procedure: MINST

Test

EXPERIMENTAL

Test intervention (MINST + CHX+HA gel): Participants will receive Minimally Invasive Non-Surgical Therapy (MINST) for the treatment of deep periodontal pockets. Immediately after instrumentation, a chlorhexidine (CHX) and hyaluronic acid (HA) gel will be applied subgingivally into the treated periodontal pockets as an adjunct to MINST. The gel is intended to provide local antimicrobial activity while supporting soft tissue healing and periodontal wound repair. Gel used: Periofix Plus GEL (Intermed S.A. Pharmaceutical Laboratories, Greece)

Procedure: MINST + CHX+HA gel

Interventions

MINST + CHX+HA gel PROCEDURE

Test intervention (MINST + CHX+HA gel): Participants will receive Minimally Invasive Non-Surgical Therapy (MINST) for the treatment of deep periodontal pockets. Immediately after instrumentation, a chlorhexidine (CHX) and hyaluronic acid (HA) gel will be applied subgingivally into the treated periodontal pockets as an adjunct to MINST. The gel is intended to provide local antimicrobial activity while supporting soft tissue healing and periodontal wound repair. Gel used: Periofix Plus GEL (Intermed S.A. Pharmaceutical Laboratories, Greece)

Also known as: Minimally invasive non surgical therapy + (CHX+HA)

Test

MINST PROCEDURE

MINST is a non-surgical periodontal treatment performed using delicate instrumentation and magnification to selectively remove subgingival biofilm and calculus while minimizing trauma to the soft and hard tissues. The technique aims to preserve gingival architecture, promote stable blood clot formation, and optimize periodontal wound healing in deep periodontal pockets

Control

Eligibility Criteria

• Age: 25 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Age 25-70 2. Diagnosis of 'periodontitis' stage III or IV (grades A to C) 3. Presence of ≥ 1 'intrabony defect' (PPD, \> 5 mm with intrabony defect depth ≥ 3 mm at screening radiograph) 4. Signed informed consent

You may not qualify if:

• \. Smoking (current or in past 5 years) 2. Medical history including diabetes or hepatic or renal disease or other serious medical conditions or transmittable diseases 3. History of conditions requiring prophylactic antibiotic coverage prior to invasive dental procedures 4. Anti-inflammatory or anticoagulant therapy during the month preceding the baseline exam 5. Systemic antibiotic therapy during the 3 months preceding the baseline exam 6. History of alcohol or drug abuse 7. Self-reported pregnancy or lactation 8. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that according to the investigator may increase the risk associated with trial participation 9. Periodontal treatment to the study site within the last 12 months

Sponsors & Collaborators

• Cairo University: lead

Study Sites (1)

Faculty of Oral and Dental Medicine. Cairo University

Giza, Giza Governorate, Egypt

Location

Related Publications (2)

• Nibali L, Koidou V, Salomone S, Hamborg T, Allaker R, Ezra R, Zou L, Tsakos G, Gkranias N, Donos N. Minimally invasive non-surgical vs. surgical approach for periodontal intrabony defects: a randomised controlled trial. Trials. 2019 Jul 27;20(1):461. doi: 10.1186/s13063-019-3544-8.

  PMID: 31351492 BACKGROUND

• Mehta J, Montevecchi M, Garcia-Sanchez R, Onabolu O, Linares A, Eriksson F, Ghezzi C, Donghi C, Lu EM, Nibali L. Minimally invasive non-surgical periodontal therapy of intrabony defects: A prospective multi-centre cohort study. J Clin Periodontol. 2024 Jul;51(7):905-914. doi: 10.1111/jcpe.13984. Epub 2024 May 6.

  PMID: 38710583 BACKGROUND

Related Links

• Minimally invasive non-surgical vs. surgical approach for periodontal intrabony defects: a randomised controlled trial. Nibali et al

MeSH Terms

Conditions

Periodontal Diseases; Periodontitis; Gingivitis; Periodontal Pocket

Condition Hierarchy (Ancestors)

Mouth Diseases; Stomatognathic Diseases; Infections; Gingival Diseases

Study Officials

• Karim Fawzy Elsayed, PhD

  Cairo University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Master's degree candidate, Cairo University

Study Record Dates

• First Submitted: July 20, 2026
• First Posted: July 28, 2026
• Study Start: March 1, 2026
• Primary Completion (Estimated): December 10, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: July 28, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)