The ideal time of systemic metronidazole and amoxicillin administration in the treatment of severe periodontitis: study protocol for a randomized controlled trial

Abstract

Background: The combination of systemic metronidazole (MTZ) and amoxicillin (AMX) with scaling and root planing (SRP) has shown to be an effective periodontal treatment. However, some essential issues associated with the use of these antibiotics remain unanswered, such as the ideal time of administration during the course of periodontal treatment. Although these agents are often prescribed after the healing phase of the SRP procedure, there is biological plausibility to support its use in conjunction with the mechanical treatment. However, to date, no placebo controlled randomized clinical trial (RCT) has directly compared these two protocols. Therefore, the aim of this RCT is to compare the clinical, microbiological and immunological effects of the adjunctive systemic MTZ + AMX administered in different phases of the treatment of severe periodontitis.

Methods: Subjects with severe periodontitis (n = 180) are being randomly assigned into three groups (n = 60/group): (i) SRP-only (control group), SRP in combination with 400 mg MTZ + 500 mg AMX, starting (ii) at the first SRP session (active phase group), or (iii) after 3 months of its completion (healing phase group). All volunteers are receiving clinical and microbiological evaluation at baseline, 3, 6 and 12 months, and immunological assessment at baseline and 12 months post-therapy. Nine subgingival biofilm samples are being collected per subject and analyzed for counts and proportions of 40 bacterial species by checkerboard DNA-DNA hybridization, and six gingival crevicular fluid samples are being collected and analyzed for the levels of 20 chemokines by multiplex immunoassay. The primary outcome variable is the number of volunteers reaching the clinical endpoint for treatment (≤ 4 sites with probing depth ≥5 mm) at 1 year post-therapy. Differences in clinical, microbiological and immunological parameters among groups and over time will be evaluated using analysis of variance, analysis of covariance and the Chi-square and Tukey tests. Microbiological and immunological analyses will be performed using adjustments for multiple comparisons. Statistical significance will be set at 5%.

Trial registration: ClinicalTrials.gov , NCT02954393 . Registered on 3 November 2016.

Keywords: Amoxicillin; Antibiotics; Metronidazole; Periodontal Disease; Periodontitis; Scaling and Root Planing; Treatment.

Conflict of interest statement

Ethics approval and consent to participate

The authors declare that the Guarulhos University Clinical Research Ethics Committee (CAAE: 32.465.714.4.1001.5506) and University of São Paulo (SP) Ethics Committee (CAAE: 32.465.714.4.2001.0075) approved the study protocol. In addition, we declare that all participants have signed the informed consent term and approved their participation in the study.

Consent for publication

Not applicable.

Competing interests

The authors declare no potential competing interests with respect to the authorship and/or publication of this article.

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Figures

Fig. 1

Experimental design of the M.O.M.E.N.T. study. CLIN: clinical assessment; MICRO: microbiological assessment; IMMUNO: immunological assessment; OHI: oral hygiene instruction; SRP: scaling and root planing; MTZ: metronidazole (400 mg/thrice daily); AMX: amoxicillin (500 mg/TID); PMT: periodontal maintenance therapy