Periodontal Wound Healing With CHX and Hyaluronic Acid (CHX+HA+ADS)

Clinical Efficacy of Chlorhexidine-based Mouthrinse Formulations in Patients Undergoing Flap Surgery: a Triple Blind, Parallel-arm, Randomized Controlled Trial

Backround: No data on the adjunctive effects of hyaluronic acid (HA) in a post-surgery, chlorhexidine (CHX) - based plaque control regimen are available. Also, contrasting evidence is available regarding the efficacy of CHX-based formulations containing anti-discoloration system (ADS). The aim of the present study was to evaluate the post-surgery gingival healing as well as plaque, gingival inflammation, and staining levels following the use of a 0.2% chlorhexidine (CHX) solution with or without anti-discoloration system (ADS) and 0.2% hyaluronic acid (HA).

Methods: Patients undergoing flap surgery at sites with an intact or reduced but healthy periodontium participated in a parallel-arm RCT. After surgery, patients used the assigned mouthrinse (CHX+HA+ADS or CHX) for 21 days. At day 7 and 21, the Gingival Healing Index (GHI) was used to assess the quality of flap closure at the interdental papilla. Plaque index (PlI), Gingival Index (GI), Angulated bleeding score (AngBS), tooth and tongue staining were also assessed.

Study Overview

• Status: Completed
• Conditions: Wound Healing; Surgical Flaps; Gingiva
• Intervention / Treatment: Device: CHX; Device: CHX+HA+ADS

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Ferrara, Italy
    • University-Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

INCLUSION CRITERIA

Patients were included in the study if positive for each of the following patient related criteria:

• 18 years or older;
• able and willing to provide a written informed consent;
• willing to grant the sufficient compliance with the experimental procedures.

Patients were included in the study if positive for each of the following surgery-related criteria (verified as part of their overall treatment plan):

• indication to at least one session of oral surgery (including periodontal surgery, endodontic surgery, tooth extraction, and implant surgery) requiring the elevation of an envelope or triangular, full-thickness gingival/mucosal flap;
• indication to flap extension to the interdental papilla between either the canine and first premolar or first and second premolar to enhance surgical visibility (teeth in this area were identified as the experimental teeth);
• intact (i.e., no clinical attachment loss) or reduced periodontium with probing pocket depths ≤ 3 mm and no diastema at experimental teeth;
• indication to the repositioning of the surgical flap at the pre-surgical level on the experimental teeth at suturing (i.e. no coronal advancement or apical displacement of the flap).

EXCLUSION CRITERIA

Patients were excluded from the study (at either recruitment or during the experimental phase) if positive for one or more of the following patient-related criteria:

• pregnancy or lactation;
• genetic defects (e.g. Down's syndrome) with an established impact on periodontal status;
• diabetes mellitus;
• immune system disorders (e.g. HIV/AIDS);
• heavy smokers (≥ 10 cigarettes/day);
• severe blood disorders, with a documented qualitative and/or quantitative deficit of polymorphonuclears and/or platelets;
• assumption of medications affecting the gingiva and/or the oral mucosa (e.g. diphenylhydantoin, calcium channel blockers, cyclosporin A, immunostimulants/immunomodulators),
• assumption of oral contraceptives;
• use of systemic or local antibiotics in the previous 4 weeks before study initiation and throughout the entire experimental phase;
• documented allergy to CHX and/or HA.

Patients were excluded from the study if the experimental teeth were positive for one or more of the following criteria:

• dental treatment within the last two months;
• presence of untreated caries or endodontic lesions;
• presence of root fractures;
• tooth alterations (i.e. amelogenesis imperfecta, tetracycline staining) impairing staining evaluations;
• presence of inadequate restorations;
• orthodontic appliances;
• indication to mucogingival surgery.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: CHX; Post-surgery use of a 0.2% chlorhexidine (CHX) mouthrinse (10 ml for 1 minute, t.i.d. for 21 days)	Device: CHX; Patients received a 21-day supply of 0.2% chlorhexidine (CHX) according to the randomization list, and were instructed to use 10 ml of the assigned mouthrinse for 1 minute, t.i.d. for 21 days. After rinsing, patients were asked to avoid washing their mouth or drinking for 30 minutes. Patients were asked to return the mouthrinse bottles (either empty of filled) at the end of the experimental period (day 21), in order to assess the level of patient compliance with the assigned CHX regimen.
Experimental: CHX+HA+ADS; Post-surgery use of a 0.2% chlorhexidine (CHX) mouthrinse containing 0.2% hyaluronic acid (HA) and Anti-Discoloration System (ADS) (10 ml for 1 minute, t.i.d. for 21 days)	Device: CHX+HA+ADS; Patients received a 21-day supply of 0.2% chlorhexidine (CHX) containing 0.2% hyaluronic acid (HA) and Anti-Discoloration System (ADS) according to the randomization list, and were instructed to use 10 ml of the assigned mouthrinse for 1 minute, t.i.d. for 21 days. After rinsing, patients were asked to avoid washing their mouth or drinking for 30 minutes. Patients were asked to return the mouthrinse bottles (either empty of filled) at the end of the experimental period (day 21), in order to assess the level of patient compliance with the assigned CHX regimen.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gingival Healing Index	The healing process was evaluated at experimental teeth using a composite index, namely the Gingival Healing Index (GHI), which was created specifically to assess the post-surgery conditions of the interdental papilla. Briefly, the interdental papillae of experimental teeth were visually inspected, and a score was assigned for the severity of wound dehiscence (1-3) and the profile of the buccal and oral aspects of the papilla (1-3). For each patient, GHI score was obtained as the sum of the scores of each variable. Therefore, GHI ranged from 2 (worst quality of healing) to 6 (optimal quality of healing).	GHI was evaluated at 7 days following surgery.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gingival Index (GI) (Löe & Silness 1963) modified by Trombelli et al. (2004)		GI was evaluated immediately before surgery and at 7 and 21 days following surgery.
Angulated bleeding score (AngBs) (van der Weijden et al. 1994) modified by Trombelli et al. (2004)		AngBS was evaluated immediately before surgery and at 7 and 21 days following surgery.
Plaque index (PlI) (Quigley & Hein 1962) modified by Turesky et al. (1970)		PlI was evaluated immediately before surgery and at 7 and 21 days following surgery.
Intensity stain index of Lobene (1968) modified by Grundemann et al. (2000)		Stain Index was evaluated immediately before surgery and at 7 and 21 days following surgery.
Tongue stain (Claydon et al. 2001)		Tongue stain was evaluated immediately before surgery and at 7 and 21 days following surgery.
Gingival Healing Index	The healing process was evaluated at experimental teeth using a composite index, namely the Gingival Healing Index (GHI), which was created specifically to assess the post-surgery conditions of the interdental papilla. Briefly, the interdental papillae of experimental teeth were visually inspected, and a score was assigned for the severity of wound dehiscence (1-3) and the profile of the buccal and oral aspects of the papilla (1-3). For each patient, GHI score was obtained as the sum of the scores of each variable. Therefore, GHI ranged from 2 (worst quality of healing) to 6 (optimal quality of healing).	GHI was re-evaluated at 21 days following surgery.

Collaborators and Investigators

• Sponsor: University Hospital of Ferrara

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2015
• Primary Completion (Actual): June 14, 2017
• Study Completion (Actual): June 14, 2017

Study Registration Dates

• First Submitted: March 6, 2018
• First Submitted That Met QC Criteria: March 13, 2018
• First Posted (Actual): March 14, 2018

Study Record Updates

• Last Update Posted (Actual): March 14, 2018
• Last Update Submitted That Met QC Criteria: March 13, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: chlorhexidine; hyaluronic acid; tooth discoloration
• Additional Relevant MeSH Terms: Wounds and Injuries
• Other Study ID Numbers: CHX+HA+ADS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No