Hyaluronic Acid for Residual Periodontal Pockets Adjunctive Treatment
Primary Purpose
Periodontitis
Status
Completed
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Hyaluronic Acid
Lidocain
Sponsored by
About this trial
This is an interventional treatment trial for Periodontitis focused on measuring hyaluronic acid, periodontitis, periodontal therapy, residual pockets
Eligibility Criteria
Inclusion Criteria:
- at least 18 years of age
- systemically healthy,
- smoking less than 10 cigarettes/day
- having been treated for periodontitis but with at least one single residual pocket of 5-9mm of depth located in the anterior area (incisors and canines)
- full-mouth bleeding score (FMBS)
- full-mouth plaque score (FMPS) less than 20%
- showing a good compliance to oral hygiene instructions
Exclusion Criteria:
- were pregnancy/lactation
- use of antibiotics in the last 3 months for a period of two weeks or more
- use of drugs causing gingival hyperplasia
- use of corticosteroids or anti-inflammatory drugs for a period of two weeks or more
- presence of diseases knowing to influence the wound healing/tissue response
- thyroid or pituitary gland malfunction or abnormal hormonal levels
- hyaluronic acid contraindications
- subjects under anticoagulant treatment
- use of systematic antibiotics for endocarditis prophylaxis
- radiation therapy in head and neck area
- use of bisphosphonate drugs prescribed for patients with osteoarthritis
- tooth mobility.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Hyaluronic acid
Lidocaine
Arm Description
After application of local anesthetic, removal of plaque and polishing of the tooth surfaces was performed followed by the local administration of hyaluronic acid gel . This adjunctive treatment was performed at baseline and at the 3 months control.
After application of local anesthetic, removal of plaque and polishing of the tooth surfaces was performed followed by the local administration of anesthetic. This adjunctive treatment was performed at baseline and at the 3 months control.
Outcomes
Primary Outcome Measures
PD (change is being assessed)
probing depth (PD) measured with periodontal probe in mm
Secondary Outcome Measures
BoP(change is being assessed)
bleeding on probing measured after probing as dichotomous parameter
Dental plaque(change is being assessed)
dental plaque measured with periodontal probe as dichotomous parameter
REC(change is being assessed)
gingival recession measured with periodontal probe in mm
Full Information
NCT ID
NCT04702334
First Posted
December 14, 2020
Last Updated
January 7, 2021
Sponsor
University of Roma La Sapienza
Collaborators
University of Rijeka, University of Zagreb, Jagiellonian University, Medical University of Sofia, University of Bern, Plovdiv Medical University
1. Study Identification
Unique Protocol Identification Number
NCT04702334
Brief Title
Hyaluronic Acid for Residual Periodontal Pockets Adjunctive Treatment
Official Title
Adjunctive Treatment of Residual Periodontal Pockets Using a Hyaluronic Acid-based Gel: A 12-month Multicenter Randomized Triple Blinded Clinical Trial
Study Type
Interventional
2. Study Status
Record Verification Date
January 2021
Overall Recruitment Status
Completed
Study Start Date
January 2016 (Actual)
Primary Completion Date
November 2018 (Actual)
Study Completion Date
November 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Roma La Sapienza
Collaborators
University of Rijeka, University of Zagreb, Jagiellonian University, Medical University of Sofia, University of Bern, Plovdiv Medical University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Objective: To evaluate the adjunctive effect of hyaluronic acid (HA) gel in the treatment of residual periodontal pockets over a 12-month period.
Materials and Methods: Periodontal patients enrolled in maintenance and presenting at least one periodontal pocket 5-9 mm of depth in the anterior area were recruited from six university-based centers. Each patient was randomly assigned to control treatment with professional mechanical plaque removal (PMPR) and local placebo application or test treatment with the adjunctive use of HA to PMPR. Clinical parameters [i.e. probing depth (PD), bleeding on probing (BoP), plaque score, recession (REC), and clinical attachment loss (CAL)] and microbiological samples for the investigation of the total bacterial count (TBC) and presence of specific bacterial strains (Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, Fusobacterium nucleatum) were taken at baseline and every 3 months, until study termination. PD was determined as the primary outcome variable.
Detailed Description
Population A total of 144 patients were enrolled from 6 university clinical centers (Sapienza University of Rome, Department of Periodontology, Rome, Italy ; University of Rijeka, School of Dental Medicine, Rijeka, Croatia; University of Zagreb, Department of Periodontology, Zagreb, Croatia; Jagiellonian University, Dental Institute, Krakow, Poland; Medical University of Sofia, Faculty of Dentistry, Sofia, Bulgaria; Medical University of Plovdiv, Faculty of Dentistry, Plovdiv, Bulgaria). The extension in time from patient recruitment to end of the protocol was January 2016 to November 2018.
The sample size was determined considering the patient level as statistical unit and probing depth (PD) as the primary outcome measure. In order to detect a mean difference of 1 mm of PD between groups with a standard deviation of 1 mm, maintaining a power of 85%, a significance level (alpha) of 0.05 and a drop-out of 25%, 12 participants per group in each center were required.
The ethical committees of each center approved the protocol of this study. The protocol followed the ethical principles of Helsinki Declaration on the good conduct of clinical trials. All patients were thoroughly informed on the treatment details and on the possibility of being excluded from the study if missing any of the 3 months follow-up appointments or showing poor compliance in general. After verbally accepting the conditions of the protocol, patients signed the informed consent prior to study initiation. Figure 1 shows step by step the study protocol that each patient followed.
Study design, randomization, allocation concealment and blinding This study was projected as a controlled randomized multicenter triple blinded 12-month clinical trial to compare the treatment of residual periodontal pockets using standard non-surgical mechanical debridement with and without hyaluronic acid gel. The detailed description of the treatment and evaluation is described in the following paragraphs.
The operators were trained and calibrated on treatment application and on PD measurement prior to study initiation. A preliminary session of PD measurements on 3 periodontal patients revealed an intra-class correlation coefficient ≥ 0.75 for each operator and among different operators.
An electronic web-based online randomization system was used for this study including a simulation version of the software for operator training prior to trial initiation. This system had been approved by the Austrian Agency for Health and Food Safety (AGES). The system parameters were set to randomization block size of 4, treatment code selection to random, using 24 treatment codes per center, and using minimization method. Centers were included as a factor for randomization process with assignment probability of 0,125 for each center (8 centers x 0,125 = 1.0) as the randomization ratio was 1:1 corresponding to treatment/ control allocation ratio.
Each operator had a username and password to perform the randomization process for each patient. An accurate audit trail showed each user log entry consisting of login-ID, center number, investigator name, event code, date, and time of which the event occurred. The system had trial specific features (role-based access control) where trial coordinators could manage each user assigned specific role determining the user's access rights. For the present study, the investigators role was to randomize without the ability to view the trial design or randomization design. The access to full control, view randomizations, un-blind randomization, was only granted to the independent trial coordinator.
Furthermore, the system provided high flexibility and security including verification for the personal email for each investigator to guarantee that each investigator will perform the randomization personally, setting a pre-defined randomization limit, the possibility to include multiple users under each center, and an effective email notification and confirmation upon each randomization performed. All transactions on the system were logged and an audit trail could be analyzed at any time by the trial monitor.
The allocation concealment was done by means of independent computerized randomization sequence process which can only be accessed by the independent trial coordinator. The investigators were provided with online login and were instructed to perform the randomization only after finishing the baseline measurements and mechanical debridement of selected tooth. To ensure that, investigators were requested to write down the exact time on provided case report forms upon finishing debridement. The computerized time stamp, electronic logs of sent allocation served as a method for monitoring allocation concealment. Furthermore, having the randomization as parallel with stratified (stratification by center) permuted blocks, served as a second layer of preventing knowledge of upcoming patient's assignment.
Clinical operators were kept blind until the moment of adjunctive treatment application allocated by the randomizer. Patients remained blinded during the entire follow-up. Microbiological evaluation and statistical interpretation of the results were made blinded on the treatment performed.
Treatment procedure Each center was provided with the same amount of HA , Eppendorf tubes, curettes , tooth paste , tooth brushes ** and interdental brushesǁ. Patients were instructed to use the modified Bass technique for brushing twice daily with the provided toothpaste free of chlorhexidine and to use the interdental brush once daily. They were instructed not to use any type of mouthwash.
All patients underwent a full mouth debridement completed within 48h in two consecutive visits. The debridement was performed using ultrasonic devices followed by curettes for all pockets of more than 4 mm. The ultrasonic treatment was repeated to ensure all surfaces were clean, followed by polishing.
At reevaluation, a tooth entering the inclusion criteria was selected. After application of local anesthetic, removal of plaque and polishing of the tooth surfaces was performed followed by the local administration of hyaluronic acid gel for the test group and local administration of anesthetic for the control group. The tip of blunt application needle mounted on the syringe containing HA was delicately inserted in the pocket until resistance was felt. The injection was performed until the remnants started getting out of the pocket. Patients were advised not to drink or eat for 2 hours. This adjunctive treatment was performed at baseline and at the 3 months control. For both groups cleaning of supragingival tooth deposits and polishing was repeated at 3, 6, 9, and 12 months.
Statistical analysis Numerical variables were reported as median (IQR) while categorical variables were reported as frequency (percentage). McNemar test was used to test for differences in proportions between time points within groups and Chi-squared test was used for differences in proportions between groups. For numerical variables, time-points differences were assessed with the Kruskal-Wallis test and pairwise comparisons were performed with Mann-Whitney U test and Wilcoxon signed rank test (for unrelated and related measurements respectively). Holms correction was used to adjust for multiple comparisons. A significance level of 0.05 was used for all statistical tests. All the analytical tests were performed using the statistical software R (version 3.6.0).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Periodontitis
Keywords
hyaluronic acid, periodontitis, periodontal therapy, residual pockets
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
All patients underwent a full mouth debridement completed within 48h in two consecutive visits.
At reevaluation, a tooth entering the inclusion criteria was selected. After application of local anesthetic, removal of plaque and polishing of the tooth surfaces was performed followed by the local administration of hyaluronic acid gel for the test group and local administration of anesthetic for the control group. The tip of blunt application needle mounted on the syringe containing HA was delicately inserted in the pocket until resistance was felt. The injection was performed until the remnants started getting out of the pocket. Patients were advised not to drink or eat for 2 hours. This adjunctive treatment was performed at baseline and at the 3 months control. For both groups cleaning of supragingival tooth deposits and polishing was repeated at 3, 6, 9, and 12 months.
Masking
ParticipantCare Provider
Masking Description
Clinical operators were kept blind until the moment of adjunctive treatment application allocated by the randomizer. Patients remained blinded during the entire follow-up. Microbiological evaluation and statistical interpretation of the results were made blinded on the treatment performed.
Allocation
Randomized
Enrollment
144 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Hyaluronic acid
Arm Type
Experimental
Arm Description
After application of local anesthetic, removal of plaque and polishing of the tooth surfaces was performed followed by the local administration of hyaluronic acid gel . This adjunctive treatment was performed at baseline and at the 3 months control.
Arm Title
Lidocaine
Arm Type
Placebo Comparator
Arm Description
After application of local anesthetic, removal of plaque and polishing of the tooth surfaces was performed followed by the local administration of anesthetic. This adjunctive treatment was performed at baseline and at the 3 months control.
Intervention Type
Drug
Intervention Name(s)
Hyaluronic Acid
Other Intervention Name(s)
Hyadent® BG, BioScience GmbH, Germany
Intervention Description
After application of local anesthetic, removal of plaque and polishing of the tooth surfaces was performed followed by the local administration of hyaluronic acid gel for the test group . The tip of blunt application needle mounted on the syringe containing HA was delicately inserted in the pocket until resistance was felt. The injection was performed until the remnants started getting out of the pocket.This adjunctive treatment was performed at baseline and at the 3 months control.
Intervention Type
Drug
Intervention Name(s)
Lidocain
Other Intervention Name(s)
Xylocaine® Dental
Intervention Description
After application of local anesthetic, removal of plaque and polishing of the tooth surfaces was performed followed by the local administration of anesthetic for the control group. The tip of blunt application needle mounted on the syringe containing HA was delicately inserted in the pocket until resistance was felt. The injection was performed until the remnants started getting out of the pocket.This adjunctive treatment was performed at baseline and at the 3 months control.
Primary Outcome Measure Information:
Title
PD (change is being assessed)
Description
probing depth (PD) measured with periodontal probe in mm
Time Frame
at baseline and at 3, 6, 9, and 12 months after being treated
Secondary Outcome Measure Information:
Title
BoP(change is being assessed)
Description
bleeding on probing measured after probing as dichotomous parameter
Time Frame
at baseline and at 3, 6, 9, and 12 months after being treated
Title
Dental plaque(change is being assessed)
Description
dental plaque measured with periodontal probe as dichotomous parameter
Time Frame
at baseline and at 3, 6, 9, and 12 months after being treated
Title
REC(change is being assessed)
Description
gingival recession measured with periodontal probe in mm
Time Frame
at baseline and at 3, 6, 9, and 12 months after being treated
Other Pre-specified Outcome Measures:
Title
microbiological measurements(change is being assessed)
Description
Total bacterial count, Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, Fusobacterium nucleatum
Time Frame
at baseline and at 3, 6, 9, and 12 months after being treated
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
at least 18 years of age
systemically healthy,
smoking less than 10 cigarettes/day
having been treated for periodontitis but with at least one single residual pocket of 5-9mm of depth located in the anterior area (incisors and canines)
full-mouth bleeding score (FMBS)
full-mouth plaque score (FMPS) less than 20%
showing a good compliance to oral hygiene instructions
Exclusion Criteria:
were pregnancy/lactation
use of antibiotics in the last 3 months for a period of two weeks or more
use of drugs causing gingival hyperplasia
use of corticosteroids or anti-inflammatory drugs for a period of two weeks or more
presence of diseases knowing to influence the wound healing/tissue response
thyroid or pituitary gland malfunction or abnormal hormonal levels
hyaluronic acid contraindications
subjects under anticoagulant treatment
use of systematic antibiotics for endocarditis prophylaxis
radiation therapy in head and neck area
use of bisphosphonate drugs prescribed for patients with osteoarthritis
tooth mobility.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Blerina Zeza, DDS,MS,PhD
Organizational Affiliation
University of Rome
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Andrea Pilloni, DDS,Msc
Organizational Affiliation
University of Rome
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Only IPD that underlie results in the publication
IPD Sharing Time Frame
once it is published
IPD Sharing Access Criteria
depending on the journal that could accept the paper
Learn more about this trial
Hyaluronic Acid for Residual Periodontal Pockets Adjunctive Treatment
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