Efficacy of Amoxicillin-metronidazole Compared to Clindamycin in Patients With Periodontitis and Diabetes
Condition: Periodontitis; Periodontal Pocket; Diabetes Mellitus
MeSH terms: Periodontitis; Periodontal Pocket; Diabetes Mellitus
Study type: Interventional
Phase: Phase 3

Summary: 
      Periodontitis is an inﬂammation of the supporting structures of the teeth, usually caused by
      speciﬁc or groups of microorganisms that results in the progressive destruction of the
      periodontal ligament and alveolar bone. the objective of periodontitis treatment is to reduce
      the number of periodontal pathogens. However, there is not an agreement in the use of
      systemic antibiotics in patients with diabetes. The purpose of the present study was to
      determine the efficacy of amoxicillin/metronidazole compared to clindamycin during
      non-surgical treatment of periodontitis in patients with type 2 diabetes mellitus.

      Patients and methods In this double-blind, randomized clinical trial, a total of 42 patients
      with chronic periodontitis and type 2 diabetes were included in a 24-months follow-up.
      Patients were randomly assigned to treatment with either amoxicillin/metronidazole or
      clindamycin every for 7 days. Clinical determinations (depth of probing, bleeding at the
      probe and plaque index) were performed to determine the extent and severity of periodontitis
      before and after the pharmacological treatment. The intra-group differences were calculated
      with Wilcoxon rank test. The inter-group differences were calculated with Mann-Whitney test.
      Sex, bacterial plaque, and bleed to the sounding were summarized using proportions and
      analyzed with the chi-square method. In all analyses, a P-value of <0.05 (two tailed) was
      considered statistically significant
    

Detailed description: 
      A parallel, randomized, double-blind, active controlled, single center clinical trial was
      designed to compare the efficacy of two antibiotic therapies with 24-month follow-up. The
      study protocol was approved by the ethical committee of the Universitary Center of Health
      Sciences of University of Guadalajara and conducted according to Good Clinical Practice and
      the principles of the Declaration of Helsinki. All patients provided written informed consent
      before the initiation of study procedures.

      A total of 5 non-study subjects with chronic periodontitis were recruited and used for the
      calibration exercise. Two designated examiners measured full-mouth probing pockets depths
      (PPD) for all 5 subjects. On the same day (with a minimum of 15 min separation), the examiner
      repeated the examination. Upon completion of all measurements, the intra-examiner
      repeatability for PPD measurement was assessed. The examiner was judged to be reproducible
      after fulﬁlling the pre-determined success criteria (the percentage of agreement within 2 mm
      between repeated measurements had to be at least 70 %). The examiner showed 78.3 %
      reproducibility.

      The sample size was calculated with a 95% confidence level and statistical power of 80 %. A
      standard deviation of 1.0 mm with an expected difference of 1.0 mm probing pocket depth
      reduction between treatments. This resulted in a total of 14 patients per arm, however this
      sample was increased 20% (21 patients per group) to compensate for possible dropouts.

      Patient population Criteria for selection Patients of both sexes (aged >18 to 70 years) with
      a diagnosis of chronic periodontitis according to the 1999 International World Workshop for a
      Classification of Periodontal Diseases and Conditions and a history of type 2 diabetes with a
      HbA1C < 8 % and a fasting plasma glucose (FPG) < 180 mg/dL. Patients with aggressive
      periodontitis, pregnant or lactating females, required antibiotic pre-medication for the
      performance of periodontal examination and treatment or received antibiotic treatment in the
      previous 3 months were excluded. A history of anti-inﬂammatory therapy within preceding six
      months or that had received a course of periodontal treatment within the last 6 months,
      allergies to penicillin, metronidazole or clindamycin, and were not able to provide consent
      to participate in the study were also criteria for exclusion.

      Intervention Subjects were randomly allocated 1:1 to receive 500 mg amoxicillin + 250 mg
      metronidazole or 300 mg clindamycin + placebo using a computer that generated a list of
      random numbers. Subjects were instructed to take the treatment three times a day for 7 days
      in both groups.

      Assessments During these sessions, a case presentation was given to each subject related to
      the speciﬁc features of his/her disease, as well as a supra- and sub-gingival mechanical
      debridement was performed. A complete periodontal examination was performed, including a full
      medical and dental history, an intra-oral examination and a full-mouth periodontal probing. A
      radiographic examination was undertaken using either periapical x-rays or a
      ortopantomography.

      Clinical parameters Clinical parameters were assessed using a North Caroline Periodontal
      Probe by the calibrated examiner at six sites. Full-mouth plaque scores were recorded by
      assigning a binary score to each surface (1 for plaque present, 0 for absent) and by
      calculating the percentage of total tooth surfaces that revealed the presence of plaque
      detected by the use of tablet. Similarly, a full-mouth percentage bleeding score was
      calculated after assessing dichotomously the presence of bleeding on probing from the bottom
      of the pocket when probing with a manual probe with a force of 0.3n. Full-mouth PPD and
      recession of the gingival margin were recorded at the same time with measurements rounded to
      the nearest millimeter.

      Non-surgical periodontal therapy Periodontal therapy was initiated within 1 month of the
      baseline screening examination. A standard cycle of periodontal therapy consisting of oral
      hygiene instructions, supra- and sub-gingival mechanical instrumentation of the root surface
      (scaling and root planning) was performed by two experienced therapists.

      Local anesthesia was used as necessary. Patients relied on standard oral hygiene methods as
      instructed at the commencement of the study.

      Post-treatment controls The objectives of the post-treatment appointments were to control and
      reinforce the oral hygiene habits of each subject, to monitor the early healing events and to
      report any adverse events or additional medications taken. In addition, the 1-week
      post-treatment visit served as a compliance control, as subjects were asked to return any
      medication not taken and/or the empty bottles. The number of pills not taken by the study
      subjects was documented.

      Re-assessment examinations Reassessment visits occurred within a month and a half of the
      completion of the pharmacological treatment. During these appointments, the examiner recorded
      any changes in the medical history and repeated clinical periodontal parameters recorded at
      the basal visit.

      Statistical analysis Age, FPG, HbA1C, tooth, and sounding depth were presented in means and
      standard deviation. The intra-group differences were calculated with Wilcoxon rank test. The
      inter-group differences were calculated with Mann-Whitney test. Sex, bacterial plaque, and
      bleed to the sounding were summarized using proportions and analyzed with the chi-square
      method. In all analyses, a P-value of <0.05 (two tailed) was considered statistically
      significant. All statistical analyses were conducted using SPSS software (IBM Corporation,
      Armonk, NY, USA) version 21.
    

Intervention name(s): Amoxicillin 500 mg / Metronidazole 250 mg; Clindamycin 300 mg
Intervention type(s): Drug; Drug
Intervention description(s): Subjects were instructed to take a capsule three times a day for 7 days; Subjects were instructed to take a capsule three times a day for 7 days
Intervention MeSH terms: Amoxicillin; Metronidazole; Clindamycin; Clindamycin palmitate; Clindamycin phosphate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Treatment
Keywords: periodontitis; diabetes mellitus; systemic antimicrobials