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| ORIGINAL RESEARCH |
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| Year : 2023 | Volume
: 15
| Issue : 4 | Page : 350-356 |
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The effectiveness of an incremental approach to nonsurgical periodontal therapy with the use of adjunctive slow-release locally administered 0.02% hypochlorite formulation: A randomized clinical study
Simone Marconcini1, Saverio Cosola2, Enrica Giammarinaro2, Giacomo Oldoini1, Annamaria Genovesi3
1 Department of Oral Surgery, Istituto Stomatologico Toscano, Lido di Camaiore, Italy
2 Department of Oral Surgery, Università Vita Salute San Raffaele, Milano, Italy
3 Department of Oral Surgery, Istituto Stomatologico Toscano, Lido di Camaiore, Italy; Department of Oral Hygiene, Università Marconi, Lido di Camaiore, Italy
| Date of Submission | 26-Dec-2022 |
| Date of Decision | 02-Jun-2023 |
| Date of Acceptance | 05-Jun-2023 |
| Date of Web Publication | 31-Aug-2023 |
Correspondence Address:
Dr. Enrica Giammarinaro
Università Vita-Salute San Raffaele, Via Olgettina 60, 20132 Milano
Italy
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/jioh.jioh_269_22
Aim: Bacterial plaque is associated with periodontal inflammation. The aim of this study was to prospectively assess the clinical effectiveness of two different agents in a staged approach for nonsurgical periodontal treatment in terms of clinical and patients related outcomes in a cohort of patients with periodontitis: NitrAdine®-based disinfectant formula (PerioTabs®) vs. Chlorhexidine (CHX) 0.12% toothpaste and mouthwash 0.20%. Materials and Methods: In the current randomized investigation, patients diagnosed with periodontal disease (stages I–III) scheduled for nonsurgical periodontal therapy were assigned at random to utilize PerioTabs®, a NitrAdine® brushing solution, or a CHX mouthwash at home. After 10–15 days of product use, active decontamination using sonic scalers and powders was carried out. The study’s outcomes were tracked at the beginning, throughout the professional intervention, and 30 and 90 days later. Assessments were made of clinical and patient-related factors. For the purposes of descriptive and inferential statistics, the chosen variables were entered into a virtual environment. Results: Forty patients were included in the final analysis. All patients showed major clinical and patient-related outcomes improvement after therapy at each time point. In the PerioTabs® group, the decrease in the bleeding score observed after the initial 10-day preparatory period (before active decontamination) was greater than in the CHX group, respectively, –45.17 ± 4.69% and –21.51 ± 2.07%. Conclusion: This study reported that the staged approach improved the clinical effectiveness of periodontal treatment in patients with periodontal disease and further suggests that PerioTabs® can be used as an efficient alternative to CHX as an adjunctive antimicrobial intervention prior to active decontamination. Keywords: Chlorhexidine, dental scaling, disinfection, periodontal diseases, sodium hypochlorite
How to cite this article:
Marconcini S, Cosola S, Giammarinaro E, Oldoini G, Genovesi A. The effectiveness of an incremental approach to nonsurgical periodontal therapy with the use of adjunctive slow-release locally administered 0.02% hypochlorite formulation: A randomized clinical study. J Int Oral Health 2023;15:350-6 |
How to cite this URL:
Marconcini S, Cosola S, Giammarinaro E, Oldoini G, Genovesi A. The effectiveness of an incremental approach to nonsurgical periodontal therapy with the use of adjunctive slow-release locally administered 0.02% hypochlorite formulation: A randomized clinical study. J Int Oral Health [serial online] 2023 [cited 2023 Sep 26];15:350-6. Available from: https://www.jioh.org/text.asp?2023/15/4/350/384660 |
| Introduction | |  |
Due to their rising frequency, periodontal diseases pose a serious threat to public health. Periodontitis may also result in tooth loss, which has an adverse effect on chewing and appearance, contributes to social inequality, and materially impairs quality of life.[1] In 2017, the consensus from the World Workshop on Periodontal Diseases classified periodontitis considering the stage and grade for each clinical case.[2] The use of the best curative and preventive therapies should be made easier by the new classification. The first treatment of periodontal disorders encompasses a wide range of therapeutic therapies with the goal of decreasing plaque accumulation and accompanying tissue inflammation, even if some patients may need surgery. The full-mouth nonsurgical periodontal treatment (NSPT), which aims to reduce the bacterial plaque of the entire mouth in a single visit, is the most popular method in the initial treatment.[3],[4],[5] However, this one-stage strategy may cause bacteremia and systemic inflammation. Additionally, patients frequently report substantial discomfort related to this surgery.[6]
The “quadrant” approach to NSPT consists of the decontamination of only one or two quadrants during the first appointment, and the treatment of the rest of the oral cavity is postponed for 1–3 weeks. During this period, patients are asked to adhere to a domiciliary oral antimicrobial therapy.[5] This method is mostly used to avoid bacteremia and the release of systemic pro-inflammatory markers.[7]
In 2014, Genovesi and colleagues proposed a modification of the traditional full-mouth disinfection (MFMD) protocol.[8],[9] In the MFMD, a two-week period of at-home use of a local antimicrobial substance, such as chlorhexidine (CHX), precedes the actual professional therapy with active decontamination. Most importantly, during the very first visit, patients are effectively motivated and trained in tooth brushing techniques and flossing. So far, the authors reported lower discomfort for the patient with this staged approach when compared to the traditional approach.[10],[11]
However, recent findings highlighted the fact that CHX may lead to resistance development in oral bacteria and in the sewage microbiome.[12],[13] Therefore, research should focus on the investigation of other products that would not interact with the microbiome and would not carry other side effects, such as teeth staining, taste loss, and numbing sensation of the oral mucosae. PerioTabs® contains a nonantibiotic biofilm removal complex called NitrAdine®.[14],[15] It works against the biofilm by causing delayed release of hypochlorite (0.02%) and surfactant-induced protein denaturation.[16],[17],[18],[19]
The aim of this clinical study was to evaluate the clinical efficacy of MFMD, either combined with the domiciliary use of PerioTabs® brushing solution or with CHX toothpaste and mouthwash in a randomized fashion.
| Materials and Methods | | |
Study design
The present manuscript adheres to the CONSORT reporting guidelines for reporting randomized clinical trials. The Istituto Stomatologico Toscano-Fortis, Forte dei Marmi (LU), Italy, hosted the current superiority, single-center, randomized clinical trial that was approved by the ethics council of Unicamillus International Medical University on April 30, 2021. NCT05846139 is the registration number for the study on clinicaltrials.gov.
Sampling criteria
Patients needed to be older than 18 and in good health, as well as have a clinical diagnosis of periodontitis. Patients should have followed the research protocol as well. The estimation of the sample size was done in accordance with earlier research.[9]
Substance misuse, treatment with bisphosphonates, anti-inflammatory medication, selective serotonin reuptake inhibitors, smoking more than ten cigarettes, pregnancy, nursing, radiotherapy for head or neck cancer, and current chemotherapy were among the exclusion criteria.
Randomization and allocation
For the distribution of patients among the two therapy groups, a randomization protocol was created using a randomization function (R version 4.0.4). Prior to therapy, sealed envelopes with the patient’s treatment allocation were opened.
Patients who agreed to participate did so by signing an informed consent form. The Declaration of Helsinki was followed in all study procedures.
Periodontitis diagnosis
The periodontitis case was classified as untreated periodontal disease stages I–III:
when there is no other explanation for the observed clinical attachment level (CAL), such as when buccal/oral CAL is less than 3 mm with pocketing more than 3 mm, and the reported CAL cannot be attributed to other reasons.[2]
Clinical and patient outcome measures
The personnel involved in the data collection was trained for two consecutive days in order to assess inter and intraoperator variability before the study commencement. The primary endpoint was to assess the change in the full mouth bleeding score (ΔFMBS). Other clinical measures included: mean pocket probing depth (PPD): a mean value of the all oral cavity; full mouth plaque score (FMPS); treatment success of NSPT as a dichotomic value.
The definitive surrogate endpoints were evaluated as “yes” or “no” with regard to the “success” (no probing depths greater than 5 mm and an FMBS% lesser than 15%, optimal improvement in all the measures, and no continuous tissue destruction for three months.
The 3-month change in oral health-related quality of life (OHrQoL) and the patient’s reported pain with visual analog scale (VAS) were also recorded as follows:
The pain reported by patients: measured with a VAS;
Patients reported outcomes: OHrQoL, scoring on a scale ranging from 0 (good influence) to 5 (negative influence), measured at T0 and T1.
The modified version of the OHrQoL survey was administered to all patients before treatment and at different time points during the 3-month follow-up.[20]
The oral health impact profile (OHIP)-14 questionnaire was administered twice so that the answers were converted into a per-patient analysis: patients were either considered worsening, stable, or improving on the observed 3-month change.
Treatment
The Genovesi MFMD approach—an incremental one—to nonsurgical periodontal therapy was pursued according to the following scheme:[10],[21]
Baseline
The usage of antimicrobial home care products, as well as tooth brushing and flossing instructions, were provided for 10 or 14 days. The diagnosis, etiology, risk factors, available treatments, anticipated risks, potential benefits, and even the option of no treatment at all were explained to the patients. Patients receive guidance on how to modify their household habits with regard to dental hygiene. At this point, patients’ local and systemic modifiable risk factors that may have had an impact on the condition (such as nutrition, exercise, and stress) were managed.
Professional treatment
Full-mouth cleaning in one stage using manual and ultrasonic tools; motivation and instruction are reviewed and reinforced.
Group 1 or test group (NitrAdine® group)
According to the product’s usage instructions, at Time 0, patients were told to use PerioTabs® at home to wash their teeth and gums every day for 10 days. During a 10-day period, the procedure involved brushing the teeth and gums for 2 min each evening. After 10–15 days, each quadrant underwent a single stage of full-mouth disinfection using ultrasonic technology.
Group 2 or control group (control group)
At baseline, patients were instructed to use a manual toothbrush at home for 15 days while using toothpaste containing 0.12% CHX. Cleaning teeth twice each day. A mouthwash containing 0.2% CHX is required to be used every night for 15 days as well. After 10–15 days, each quadrant underwent a single stage of full-mouth disinfection using ultrasonic technology. In addition, two 90-s cycles of ozone therapy were performed.
Follow-up
Following initial medication, patients were monitored for three months as per the following schedule: T0: Baseline and oral hygiene education session; T1: whole mouth debridement 10–14 days after T0; T2: 30 days after T0; T3: 90 days following T0. Clinical results were assessed both at the beginning and at each subsequent session. The OHrQoL questionnaire was administered at baseline and 90 days after T0 (T3), and the VAS for pain was collected at baseline and T1.
Statistical analysis
Data were entered into the statistical free software R. For the analysis of intergroup comparisons of continuous variables, two-sample t-tests were conducted to detect differences between the two study groups. Odds ratios were used to assess categorical data. The VAS reading was computed as the function of time and the other covariates. In the end, a custom continuous ordinal model was built with a specific function within R. The alpha error was fixed at <0.05 for each test.
| Results | | |
Forty patients were included in the analysis. Twenty patients were included in the test group and 20 in the control group. All 40 subjects completed treatments and follow-up evaluations. The intention-to-treat approach was used. Patients were followed from the moment of recruitment (enrollment started in 2021) up to three months after treatment. The overall mean age was 50.08 ± 12.26 years. The demographic information at baseline with the explanatory measures for both the test and the control group are summarized in [Table 1]. Gender, age, or smoking habits did not differ significantly between the two study groups (P value <0.05).
Clinical evaluation
[Table 2] summarizes the clinical measures collected at each time point with their average values. The longitudinal evaluation demonstrated that, for each patient, all clinical variables were improved over time and at each time-point (P < 0.01), excluding PPD [Figure 1]A–C. The intergroup analysis showed significant differences in FMBS (%) at T1, thus after 10–15 days of patients’ self-care at home: patients in the PerioTabs® group showed the greatest reduction in the bleeding score from motivation session whit respect to the CHX group (P < 0.05), respectively 45.17 ± 4.69 and 21.51 ± 2.07 [Figure 2]. T T3, 19 patients in the PerioTabs® group showed “periodontal success,” while in the CHX group, 18 patients had “periodontal success.” | Table 2: Mean pocket probing depth (mean value ± SD), FMBS (%), FMPS (%), and respectively P-value, P < 0.05 in bold
Click here to view |
 | Figure 1: (A) Female patient from the test group at T0, before the periodontal record; (B) same patient at T1 displaying the clinical appearance of the gingiva after motivation and instruction for 10 days of domiciliary PerioTabs®-therapy; (C) at T2, the clinical aspect of gingiva after 30 days from the motivation and 20 days after the full-mouth disinfection
Click here to view |
Patient-related outcomes
Patient-related outcomes improved for both groups over time and at each time point (P < 0.001). Despite not reaching statistical significance, patients in the PerioTabs®-group reported better scores for pain (VAS) and OHrQoL [Table 3]. No complications or side effects were recorded in any of the two groups. | Table 3: VAS (0–10) and OHrQoL (OHIP-14) with respectively P values, P < 0.05 in bold
Click here to view |
| Discussion | | |
The present study’s findings confirmed the effectiveness of an incremental strategy for the early management of periodontal disease. All patients reported decreased plaque accumulation, reduced discomfort and inflammation, and improved oral health conditions following the initial visit that included information and incentive, with the patient’s active participation and 10–14 days of home intervention. The average pocket probing depth did not change significantly, and this result is in line with PPD being not sensitive enough a parameter when employed in short-term investigations.[22]
Patients assigned to the use of PerioTabs® achieved better results, with lower FMBS (%) after 10–15 days of domestic use. The initial reduction in inflammation attained with the MFMD strategy may account for the lack of difference in other parameters; patient education and motivation may have allowed them to play a crucial part in the effectiveness of the treatment.
The authors of the 2020 EFP Research Group underlined that periodontal treatment should include oral hygiene instructions and patient incentives for good dental hygiene habits.[1] They also consider the feasibility of using locally given sustained-release CHX as an additional treatment for patients with periodontitis in addition to instrumentation.
A mouthwash containing CHX before surgery can reduce the bacterial count and subsequently postpone the formation of new biofilms, according to Sekino et al.[23] The local microbiota naturally tends to return to its initial composition three hours after the antibacterial action of 2% CHX wears off.[24] Even worse, the balance could shift toward more acidic conditions.[25],[26]
The current study revealed increases in OHrQoL following expert therapy for periodontal disease in terms of patient-related outcomes. This result was Icoherent with other studies like Fuller et al.,[27] who evaluated the longitudinal clinical difference with an improvement of five points regarding QoL related to oral status after periodontal treatment; the advantages of the home oral care instructions and motivation not only result in improved plaque control but also in the patient’s wellness and comfort.
No unintended consequences with PerioTabs® were noted in this trial, but two patients in the control group reported no appreciable clinical improvement following periodontal therapy. Four patients in the CHX group also had upper teeth that were stained, were numb, and had altered tastes. This is consistent with findings from a recent trial conducted by Haydari et al.[28] to examine the impact of CHX on a gingivitis model. In their study, 65%–60% of included patients complained about the common side-effects of CHX, the ageusia, and the numbness feeling.
Additionally, a low-concentration bactericidal agent like CHX may pose a risk for the emergence of resistance in oral bacteria. Increased usage of low-concentrate CHX in oral and general healthcare could lead to the emergence of resistance to this adaptable antiseptic.[29] Thus, the microbiome will eventually produce more CHX-resistant bacteria.
The therapeutic usefulness of a phased approach for the treatment of periodontal disease is further supported by the new information provided by this study. There is evidence that the majority of the game is played at the beginning when the patient is first informed, inspired, and instructed. To support the current findings, additional research with bigger populations and further patient stratification are required.
| Conclusion | | |
This randomized trial supported the clinical effectiveness of an incremental approach in the treatment of periodontitis and further suggested that the slow release of locally administered 0.02% hypochlorite formulation might be a valid alternative to CHX as an adjunctive chemical intervention with this protocol.
Acknowledgement
A sincere thanks to Bonyf, Liechtenstein, for supporting this study with materials.
Financial support and sponsorship
This study was supported by Istituto Stomatologico Toscano.
Conflicts of interest
There are no conflicts of interest.
Authors contribution
Conceptualization: SM and AG; Data acquisition: GO, AG, and SC; Formal analysis: EG and SC; Funding: AG; Supervision: SM and AG; Writing-original draft: SM, EG, GO, AG, and SC; Writing-review and editing: SM, EG, GO, AG, and SC.
Ethical policy and institutional review board statement
Single-center, randomized clinical trial that was approved by the ethics council of Unicamillus International Medical University on April 30, 2021. NCT05846139 is the registration number for the study on clinicaltrials.gov.
Patient declaration of consent
Not applicable.
Data availability statement
Data files are available upon request.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]
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