Comparative evaluation of Clarithromycin Gel and Chlorhexidine Gel as local drug delivery agents as an adjunct to scaling and root planing in the management of patients with chronic periodontitis (stageIII gradeB)-A clinico-microbiological study.

TITLE:-

Comparative evaluation of Clarithromycin Geland Chlorhexidine Gel as local drug delivery agent as an adjunct to scaling androot planing in the management of patients with chronic periodontitis (stageIIIgradeB)– A clinico-microbiological study.

INTRODUCTION:-

The term"periodontitis" originates from two words, i.e.,"periodont-" meaning "structure surrounding the teeth" and"itis" means "inflammation."

Chronic periodontitis is defined as aninflammatory disease of tooth‑supporting tissues and if not treated, can leadto progressive attachment loss causing destruction of the tissues, which is clinicallycharacterized by gingival bleeding, progressively increasing pocket depth,clinical attachment loss and alveolar bone loss, which eventually results inteeth loss. The prevalent etiology for periodontal diseases is the complex ofdysbiotic microbiota present in dental plaque biofilm.

600 different species of bacteria are presentand colonize in the oral cavity which alter the balance of host-bacterialinteractions ultimately leading to periodontal disease.

Gram-negative anaerobic bacteria, such as Porphyromonasgingivalis (P.gingivalis), A. actinomycetemcomitans, *Prevotella intermedia, Tannerella forsythia, *Treponema denticola**Streptococcus oralis, Streptococcus intermedius, Peptostreptococcus micros, andFusobacterium nucleatum are dominant flora associated with chronicperiodontitis. Among all these microorganisms Porphyromonas gingivalis, *Treponema denticola, Tannerella forsythia forms the Redcomplex which are considered to be associated with chronic periodontitis.*In chronic periodontitis 85% of diseased site is mostly associated withP.gingivalis. The disease progression in periodontal pocket may be predicted bythe increase of P.gingivalis. Hence reduction in count of P.gingivalis isanalogous with resolution of disease at affected site.

Scaling and root planing (SRP) is still the benchmarkfor nonsurgical treatment of chronic periodontitis, but it has certainlimitations such as incomplete removal of calculus from the posterior teeth orteeth having pocket depth 3mm. Toovercome these problem surgical therapy was developed but long term therapy didnot show any superior results in term of periodontal attachment gain. Thus antimicrobialscame into existence which have proven beneficial after non-surgical andsurgical therapy.

Antimicrobials are available in various local drug delivery (LDD) forms such asChlorhexidine (CHX), Clarithromycin (CLM), Tetracyclines, Metronidazole,Azithromycin, Moxifloxacin, Simvastatin, Metformin and Alendronate which arepresently being used in various drug delivery systems such as irrigations, fibers,films, injectable, gels, strips, compacts, vesicular liposomes, microparticles,and nanoparticle systems in the management of periodontal disease.

Over other preparations gel formulations have moreadvantages. Gels can be more easily prepared and administered. They also haveproperties of higher biocompatibility and more bioadhesive allowing easyadhesion into the periodontal pocket, sustained drug release pattern, minimumdose frequency, and drug toxicity.

Clarithromycin and Azithromycin are macrolideantibiotics which are relatively new in terms of local application in themanagement of periodontal disease.

Macrolide antimicrobials are well endured andgive a sound alternative for the treatment of odontogenic and periodontalinfections. CLM is accumulated by phagocytes, monocytes,fibroblasts, polymorphonuclear cells, macrophages, and lymphocytes. One couldexpect greater benefits, as these cells are more prevalent at periodontaldisease sites.

CLM has broad antimicrobial spectrum againstPeriodontal pathogens i.e P.gingivalis, better bioavailability, favorabletissue distribution, a low incidence of adverse drug reactions, highconcentration in GCF and remains in GCF for long duration.

0.5%CLM gel when incorporated into subgingival periodontal pockets gives benefittill 6 months after application.

Chlorhexidine isthe gold standard agent with which other antiplaque and antigingivitis agentsare compared. The effectiveness of this agent depends on bactericidal andbacteriostatic effects and its substantivity in the oral cavity.

The introduction of LDD system inperiodontal pocket gives promising clinical and microbiological outcomes andalso enhances periodontal health when used as adjunct to nonsurgical periodontaltherapy.Hence the rationale of this study is to comparativelyevaluate the clinical and microbiological effects of subgingivally delivered0.5% Clarithromycin gel and 0.2% Chlorhexidine gel as an adjunct to SRP fortreating Chronic periodontitis patients (stageIII gradeB).

**AIM OF THE STUDY:-**The aimof thestudy is to evaluate the clinical & microbiological parameters using 0.5%Clarithromycin Gel and 0.2% Chlorhexidine Gel as a local drug delivery agent asan adjunct to scaling and root planing in the management of patients with  periodontitis (stageIII gradeB).

OBJECTIVE:-

Primary objective:-

To evaluate and compare the effects of 0.5%Clarithromycin gel and 0.2% Chlorhexidine gel used as an adjunct to SRP in thetreatment of subjects with periodontitis (stageIII gradeB) as seen by change inclinical parameters at baseline, 6 weeks, and 3months and change in microbialparameter at baseline and 6 weeks respectively.

OTHER OBJECTIVE 1:-

1)To evaluate the effect of 0.5%Clarithromycin gel with SRP on clinical periodontal parameters at baseline, 6weeks & 3months & microbiologic parameters at baseline, 6weeksrespectively in patients of periodontitis (stageIII gradeB).

2)To evaluate the effect of 0.2% Chlorhexidinegel with SRP on clinical periodontal parameters at baseline, 6 weeks &3months & microbiologic parameters at baseline, 6weeks respectively inpatients of periodontitis (stageIIIgradeB).

OTHER OBJECTIVE 2:-

To find out the best effect among LDD agent 0.5% Clarithromycingel & 0.2% Chlorhexidine gel  whenused  as an adjunct to scaling and rootplaning in the treatment of the subjects with periodontitis(stageIII gradeB) asevaluated by change in clinical parameters of PI, GI, mSBI, PPD, CAL atbaseline, 6 weeks, and 3months and change in microbial parameter includingbacterial load of P.gingivalis at baseline and 6 weeks respectively.

METHODOLOGY:-

STUDY DESIGN:-

This is a randomizedclinical and microbiological split mouth study.

STUDY SETTING:-

The study would beconducted abiding by all human ethical principles as per the WMA- Declarationof Helsinki and the Guidelines of Good Clinical Practice (ICMR) will beobserved. The study will be performed with each subject unaware of whichintervention each study tooth is being subjected to. Measurements of theevaluation parameters will be performed by a nonblinded single trained operator.The statistician shall however be blinded to the intervention groups.

STUDY POPULATION:-

The study will be performed on systemicallyhealthy volunteer subjects screened for inclusion criteria by simple random sampling from theirpresentation for examination at the Dental college after fulfilling the inclusion criteria and rendering informedconsent through signed document in English and local language to participate inthe study over a study period of 3 months from baseline.

Sample size:-

·      The calculated sample size is 26 patients (52sites).

Sampling technique:

·      The study will be conducted in patients having periodontitis (stageIII gradeB).

·      An informed consent will be taken in local and English language.

·      The test and control group are as follows-

Control group – Patientundergoing SRP + 0.2%chlorhexidine gel

Test group – Patient undergoingSRP + 0.5%clarithromycin gel

Inclusion criteria:

·      Both male and female patients with generalized chronic periodontitis (stageIII gradeB).

·      Age group between 35-60 years with good systemic health.

·      Minimum 20 teeth should be present in the mouth of patients.

Periodontitispatient with atleast 2 non-adjacent teeth in 2 contralateral quadrants with CAL> 3mm and PPD 4-6mm.

Patients with no history of allergies.

Exclusion criteria:

·      Patients suffering from any known systemic diseases.

·      Smokers and alcoholic patients.

·      Medicationtaken by patient that would induce gingival enlargement.

·      Pregnancy or lactating female patients.

·      Patients who have received surgical or nonsurgicalperiodontal therapy in last 3 months prior to the baseline visit.

·      Patients who received systemic antimicrobial therapy in last 2months prior to entry.

·      Patientswho have received clarithromycin and chlorhexidine gel in the past.

·      Patients who have received any antibiotics, chemotherapeuticmouth rinse or oral irrigation during past 3 months.

·      Patients allergic to any medication.

EVALUATION PARAMETERS

I) Plaqueindex (PI) (Silness and Loe, 1964)

II)Gingival Index (GI) (Loe and Silness, 1963)

III) Modified Sulcusbleeding index (mSBI) (Mombelli, M.A.Van Oosten, E.Schurch.Jr &N.P.Land 1987

IV)PROBING POCKET DEPTH(PPD)

V) Clinicalattachment level(CAL)

VI) Microbiologicalanalysis:-

Microbiological analysis will be done atbaseline and at 6weeks.

Tris-EDTAbuffer (TE buffer) has been provided as transport media in sterile vials.

The vialscontaining transport media can be stored in refrigerator (4ºC) for around onemonth. The vials are discarded if TE buffer gets turbid.

Visible amount of plaque sample is collected from both test and control site atbaseline and 6weeks using Universal curettes (2R-2L, 4R-4L).

Plaque sample is then immediately transferred to the TE buffer vials andlid is closed.

The collectedsamples can store in a refrigerator (4ºC) for maximum 2 days before sending thevials to laboratory.

PROCEDURE:-

·      Thiswill be a split mouth design study.

·      Thepatients will be subjected to careful oral examination under properillumination.

·      Abrief case history will be recorded from all 26 patients

·      Aninformed consent will be taken from each of them.

·      Atotal number of 13 patients with 26 sites each will be randomized into 2treatment groups (13 sites in each group). In test group,sites will be treated with SRP followed by placement of prepared 0.5% CLM agentand inthe control group site will be treated with SRP followed by placement of 0.2%CHX.

Periodontal status will be assessed at baseline preoperatively and at6weeks and 3 months postoperatively by using Plaque Index (Silness & Loe1964), Gingival Index (Loe & Silness 1963)Modified SulcusBleeding Index. Probing pocket depth and clinical attachment level will bemeasured by acrylic stent using a color-coded periodontal probe (UNC 15color-coded periodontal probe; Hu-Friedy, Chicago,).

·    For microbiological analysis plaque samples willbe collected from test and control site in contralateral quadrant andtransferred into Tris-EDTA buffer (transport media vials).

·     At baseline afterclinical and microbiological parameters are assessed, patient will undergo SRP untilthe root surface is considered smooth and clean by the operator. After completion ofSRP, prepared local drug delivery agents (0.5% CLM gel and 0.2%CHXgel) will be placed in the periodontal pocket of each quadrants in the patients. Thisplacement will be done by 24gauge angulated blunt cannula syringeuntil it will be detected at the gingival margin.

·      In each patient only one site in one quadrantwill be enrolled for either the CLM or CHX. Patients will be masked forallocation into the CLM or CHX groups.

·       To ensure retentionof the gel to be effective in the pocket, a periodontal dressing (CoePak) willbe given for seven days.

·      No antibiotics or anti-inflammatory agentswill be prescribed after treatment.

·      Postoperative home care brushing instructions willbe given.