MTZ Plus AMX in the Treatment of Smokers and Non-smokers
Condition: Chronic Periodontitis; Smoking
MeSH terms: Periodontitis; Chronic Periodontitis
Study type: Interventional
Phase: Phase 4

Summary: 
      Randomized controlled clinical trials have demonstrated that the use of amoxicillin (AMX) and
      metronidazole (MTZ) as adjuncts to mechanical therapy improves the clinical and
      microbiological outcomes of scaling and root planing (SRP) in non-smokers and smokers with
      ChP. However, the effects of this antibiotic protocol have not been directly compared in
      non-smokers and smokers. Therefore, the aim of this study will be to compare the clinical and
      microbiological effects of the adjunctive use of MTZ+AMX to SRP in smokers and non-smokers
      subjects with chronic periodontitis (ChP). It was hypothesized that non-smokers would benefit
      better from this combination of therapies than the smokers.
    

Detailed description: 
      Sample size calculation:

      This study is designed to compare the clinical and microbiological effects of the treatment
      of smoker and non-smoker subjects with SRP+MTZ+AMX. The ideal sample size to assure adequate
      power for this clinical trial was calculated considering differences of at least 1mm between
      groups for clinical attachment level (CAL) in initially deep periodontal sites (PD ≥ 7 mm).
      It was also determined that the standard deviation of CAL change at deep sites would be 1.0
      mm based on our earlier studies of smokers and non-smokers receiving SRP combined with
      MTZ+AMX. Based on these calculations, it was defined that 26 subjects per group would be
      necessary to provide an 85% power with an α of 0.01. Considering an attrition of about 20%,
      it was established that at least 32 subjects should be included in each treatment group.

      Experimental design and treatment protocol:

      In this cohort clinical trial, subjects will be assigned according to their smoking status,
      into smoker and non-smoker groups. All subjects will receive SRP combined with systemic MTZ
      (400 mg) and AMX (500 mg). Both antibiotics will be administered T.I.D. for 14 days. Before
      the study begins, all subjects will receive full-mouth supragingival scaling and instruction
      on proper home-care techniques. They will receive the same dentifrice to use during the study
      period (Colgate Total). All subjects will receive full-mouth SRP performed under local
      anesthesia in four to six appointments lasting approximately 1h each. Treatment of the entire
      oral cavity will be done in 14 days. SRP will be performed by one trained periodontist using
      manual instruments. The antibiotic therapies will start immediately after the first session
      of mechanical instrumentation. The University Pharmacy will prepare the antibiotic pills and
      send them to the study coordinator, who will mark the code number of each subject on a set of
      two packs and give them to the examiner. All subjects will receive clinical and
      microbiological monitoring at baseline and at 3, 6 and 12 months post-therapy.

      Clinical monitoring:

      One calibrated examiner will perform clinical monitoring and the treatment will carried out
      by another clinician. Thus, the examiner and the clinician will be masked as to the nature of
      the treatment groups. Visible plaque (presence or absence), gingival bleeding (presence or
      absence), bleeding on probing (BOP; presence or absence), suppuration (presence or absence),
      PD (mm) and clinical attachment level (CAL, mm) will be measured at six sites per tooth
      (mesiobuccal, buccal, distobuccal, distolingual, lingual and mesiolingual) in all teeth,
      excluding third molars. The PD and CAL measurements will be recorded to the nearest
      millimeter using a North Carolina periodontal probe.

      Microbiological Monitoring:

      Subgingival plaque samples will be collected at baseline and at 3, 6 and 12 months post-SRP
      from nine non-contiguous interproximal sites per subject. The select sites will be randomized
      in different quadrants and subset according to baseline PD, three samples in each of the
      following categories: shallow (PD<3 mm), intermediate (PD 4-6 mm) and deep (PD>7 mm). After
      the clinical parameters have been recorded, the supragingival plaque will be removed and the
      subgingival samples will be taken with individual sterile curettes (Gracey #11-12) and
      immediately placed in separate Eppendorf tubes containing 0.15 ml of buffer (TE). One hundred
      microliters of 0.5 M sodium hydroxide (NaOH) will be added to each tube and the samples will
      be dispersed using a vortex mixer. The samples will be analyzed by Checkerboard DNA-DNA
      hybridization.
    

Intervention name(s): Metronidazole plus Amoxicillin
Intervention type(s): Drug
Intervention description(s): All subjects will receive scaling and root planing combined with systemic metronidazole (400 mg) and amoxicillin (500 mg). Both antibiotics were administered T.I.D. for 14 days.
Other intervention name(s): Metronidazole; Amoxicillin; Scaling and root planing
Intervention MeSH terms: Amoxicillin; Metronidazole
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Periodontal disease; Scaling and root planing; Metronidazole; Amoxicillin; Generalized chronic periodontitis; Periodontal treatment