<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02223702</url>
  </required_header>
  <id_info>
    <org_study_id>KOUKAEK5/9</org_study_id>
    <nct_id>NCT02223702</nct_id>
  </id_info>
  <brief_title>Alternative Antibiotic Regime in the Treatment of GAgP</brief_title>
  <official_title>Clinical Evaluation of Systemic Moxifloxacin Compared to Amoxicillin Plus Metronidazole Adjunct to Non-surgical Treatment in Generalized Aggressive Periodontitis: A Randomized Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kocaeli University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Kocaeli University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objective of this randomized clinical study was to evaluate the effect of systemic&#xD;
      administration of moxifloxacin compared to amoxicillin plus metronidazole combined with&#xD;
      non-surgical treatment in patients with generalized aggressive periodontitis (GAgP) in&#xD;
      6-month follow-up.&#xD;
&#xD;
      A total of 40 systemically healthy patients with GAgP will evaluate in this randomized&#xD;
      clinical trial. Periodontal parameters (plaque index, gingival index, probing depth, bleeding&#xD;
      on probing, clinical attachment level) will be recorded at baseline, 1st, 3rd and 6th month.&#xD;
      Patients will receive either 400 mg moxifloxacin per os once daily or 500 mg metronidazole&#xD;
      and 500 mg amoxicillin per os three times daily for 7 days consecutively.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The American Academy of Periodontology and the European Federation of Periodontology were&#xD;
      reported that patients with GAgP may have benefit from adjunctive administration of&#xD;
      antibiotics. Antibiotics are used as an adjunct to nonsurgical treatment either locally or&#xD;
      systemically. Systemic antimicrobial agents as adjunct to nonsurgical treatment provide&#xD;
      additional benefits over mechanical therapy alone in terms of probing depth reduction and&#xD;
      periodontal attachment gain.&#xD;
&#xD;
      Amoxicillin is a moderate spectrum, bacteriolytic β-lactam antibiotic, and metronidazole&#xD;
      which is active against anaerobic bacteria is a nitroimidazole. scaling and root planing&#xD;
      combination with metronidazole plus amoxicillin therapy was found to be more effective in&#xD;
      suppressing P. gingivalis and eradication of A. actinomycetemcomitans and preventing&#xD;
      re-colonization of A. actinomycetemcomitans because of the synergistic effect of this&#xD;
      combination and their wide spectrum of activity. It was found to be superior to azithromycin,&#xD;
      doxycycline, and metronidazole in the treatment of GAgP.&#xD;
&#xD;
      Quinolones were introduced for use in urinary tract infections in the 1970s. Moxiflocaxin is&#xD;
      a fourth generation fluoroquinolone antibiotic exhibits good tissue penetration and high oral&#xD;
      bioavailability and has improved activity against Gram- positive, aerobic and anaerobes.&#xD;
      Moxifloxacin is used in the systemic treatment of respiratory infections, acute sinusitis,&#xD;
      odontogenic abscesses, osteomyelitis of the mandible and locally in the treatment of&#xD;
      ophthalmic infections.&#xD;
&#xD;
      Moxiflocaxin has good activity against putative periodontal pathogens, including&#xD;
      Porphyromonas gingivalis, Tanneralla forsythia, Prevotella spp, Fusobacterium nucleatum,&#xD;
      Actinomyces spp, Campylobacter rectus, Peptostreptococcus spp. and Aggregatibacter&#xD;
      actinomycetemcomitans, located within biofilm or intracellulary. It was shown that A.a.&#xD;
      strains were highly susceptible to fluoro-quinolones ciprofloxacin and moxifloxacin. Some of&#xD;
      the adjunctive antibiotics are secreted in saliva in insufficient concentrations to inhibit&#xD;
      A.a. Moxifloxacin seems to be secreted in saliva at higher levels than in plasma and may also&#xD;
      concentrate at the site of infection since it penetrates polymorphonuclear granulocytes and&#xD;
      epithelial cells. Moxifloxacin was found to be superior to clindamycin, metronidazole or&#xD;
      doxycycline.&#xD;
&#xD;
      Systemic administration of moxifloxacin as an adjunct to scaling and root planing was found&#xD;
      to be more effective compared to scaling and root planing alone or scaling and root planing&#xD;
      in conjunction with doxycycline in the treatment of severe chronic periodontitis. To best our&#xD;
      knowledge, there is no study that evaluates the effect of moxifloxacin adjunct to scaling and&#xD;
      root planing in the treatment of GAgP.&#xD;
&#xD;
      The aim of this single center, randomized clinical study was to evaluate the impact of&#xD;
      adjunctive systemic moxifloxacin compared to the use of adjunctive systemic amoxicillin and&#xD;
      metronidazole during full-mouth scaling and root planing on the success of the treatment of&#xD;
      patients with GAgP with 6-month follow-up. The hypothesis was the use of adjunctive systemic&#xD;
      moxifloxacin would provide the similar clinical results as adjunct systemic amoxicillin and&#xD;
      metronidazole during scaling and root planing.&#xD;
&#xD;
      This study was a single-center, randomized, parallel-design clinical trial with 6 month&#xD;
      follow-up. It was conducted at Kocaeli University, Faculty of Dentistry, Department of&#xD;
      Periodontology between 2011-2013. The study protocol was approved by the Ethics Committee of&#xD;
      the Medical Faculty of Kocaeli University (KOU KAEK 5/9) and was conducted in accordance with&#xD;
      the Helsinki declaration of 1975, as revised in 2000.&#xD;
&#xD;
      The GAgP patients were recruited from patients seeking periodontal treatment at Kocaeli&#xD;
      University, Faculty of Dentistry, Department of Periodontology, Kocaeli, Turkey.&#xD;
      Approximately, 12.000 patients were screened the dates between June 2011 and September 2012.&#xD;
      A complete medical, dental, periodontal and radiographic examination was performed. The study&#xD;
      protocol explained to the patients. From patients who willing to participate to the study,&#xD;
      written informed consent was obtained and included the study.&#xD;
&#xD;
      The periodontal diagnosis of subjects with GAgP was established on the basis of clinical and&#xD;
      radiographic criteria defined by the 1999 International World Workshop for a Classification&#xD;
      of Periodontal Diseases and Conditions. Patients were included if they were between 18 and 35&#xD;
      years of age and otherwise healthy. The bone loss estimation was radiographically performed&#xD;
      in each patient for the assessment of the extent and severity of alveolar bone loss. Medical&#xD;
      and dental histories were questioned. Subjects were excluded if they had any known systemic&#xD;
      diseases or conditions that can/could influence the periodontal status (cancer,&#xD;
      cardiovascular and respiratory diseases), history of hepatitis or HIV infection,&#xD;
      immunosuppressive chemotherapy, current pregnancy, planning a pregnancy or lactation,&#xD;
      requirement for antibiotic prophylaxis, oral diseases other than GAgP, ongoing orthodontic&#xD;
      therapy, a history of antibiotic therapy or periodontal treatment within the preceding six&#xD;
      months. Subjects were excluded if they had known allergies to quinolones or penicillin or&#xD;
      metronidazole.&#xD;
&#xD;
      Periodontal Examination The full-mouth clinical periodontal measurements were recorded at 6&#xD;
      sites per tooth (mesio-buccal, mid-buccal, disto-buccal, disto-lingual, mid-lingual, and&#xD;
      mesio-lingual) including plaque index (PI), gingival index (GI), probing depth (PD), bleeding&#xD;
      on probing (BOP) and clinical attachment level (CAL). CAL was calculated from the&#xD;
      cement-enamel junction to the base of the periodontal pocket. Williams periodontal probe was&#xD;
      used for periodontal measurements. All measurements and scaling and root planing were&#xD;
      performed by the same single calibrated and trained periodontist in a standardized manner.&#xD;
&#xD;
      Allocation concealment The patients were randomly assigned to one of the study groups. To&#xD;
      ensure complete masking of allocation, before the recruitment of the patients, forty&#xD;
      identical, opaque-colored, impermeable plastic bags which include toothbrush, interproximal&#xD;
      brush, toothpaste and either moxifloxacin or amoxicillin and metronidazole were prepared and&#xD;
      coded. A code number was given to each subject. Randomization codes were kept separately from&#xD;
      the clinical evaluation forms by one of the authors until the treatment and follow-up visits&#xD;
      were completed. The examiner who performed the treatment was unaware of the allocation.&#xD;
&#xD;
      Prior to treatment, all subjects were gone through motivation sessions for oral hygiene.&#xD;
&#xD;
      Following to periodontal measurements, full-mouth supragingival scaling using ultrasonic&#xD;
      scaler and polishing were performed, and a toothbrush, toothpaste and an interproximal&#xD;
      toothbrush were provided to all subjects. One week later, the patients were examined for&#xD;
      plaque accumulation and oral hygiene. The patients who cannot maintain proper oral hygiene&#xD;
      were excluded from the study. Only 39 patients fulfilled the qualification criteria for&#xD;
      enrollment for the present study.&#xD;
&#xD;
      Subjects were randomly assigned to receive one of the two treatment groups. Moxifloxacin&#xD;
      group received scaling and root planing and an adjunctive systemic antibiotic, 400 mg&#xD;
      moxifloxacin, once in a day for 7 days and amoxicillin and metronidazole group received a&#xD;
      combination of 500 mg of amoxicillin and 500 mg metronidazole three times per day for 7 days.&#xD;
      The subjects were instructed to take first dose of the antibiotics in the morning of the&#xD;
      first session since the microorganisms are organized on the root surface and protected from&#xD;
      antimicrobial agents. Scaling and root planing were performed on 2 consecutive days in 24&#xD;
      hours under the local anesthesia. On each day, scaling and root planing were performed in 2&#xD;
      quadrants using ultrasonic scalers and manual instruments . The endpoint of scaling and root&#xD;
      planing was a tactile smooth root surface.&#xD;
&#xD;
      The subjects were insistently informed about the intake of the antibiotics properly, and they&#xD;
      asked to inform the researches if they needed to take another antibiotics or&#xD;
      anti-inflammatory agents for another reason during and following the study for 6 months.&#xD;
&#xD;
      Patients used a 0.2% chlorhexidine digluconate rinse twice a day for a month and brushed&#xD;
      their teeth by tooth brushes and interproximal tooth brushes twice a day. Patients asked to&#xD;
      report any adverse events and side effects of the antimicrobial agents as soon as possible.&#xD;
&#xD;
      Subjects were monitored one week after the second scaling and root planing session. At this&#xD;
      session, antibiotic intake, adverse events and side effects were questioned; oral hygiene and&#xD;
      plaque accumulation were controlled. Subjects were screened at 1, 3 and 6 months after&#xD;
      completion of nonsurgical treatment. During these sessions, clinical periodontal parameters,&#xD;
      any medical history change, especially, whether antibiotic therapy had been prescribed for&#xD;
      any reason was recorded. At the end of these sessions, supragingival scaling was performed,&#xD;
      if needed.&#xD;
&#xD;
      The present study was conducted within in the same clinic, and the patients were taken to the&#xD;
      same dental chair and treated with a same experienced periodontist for to discard&#xD;
      discrepancies and to provide standardized and controlled environment.&#xD;
&#xD;
      Sample size calculation&#xD;
&#xD;
      The primary outcome variable was probing depth changes. The sample size was calculated based&#xD;
      on previous information from a study conducted in our department, using data relative to the&#xD;
      mean difference and standard deviation (SD) between the experimental periods for the probing&#xD;
      depth parameters.57 Considering a mean probing depth difference of 1.3 mm between evaluation&#xD;
      periods, it was estimated that 13 patients for each group would be necessary to provide 95%&#xD;
      power (0.54 SD, α error of 0.05, and β error of 0.2).58 However, we aimed to recruit 20&#xD;
      patients to each group if we lose to follow the patients during the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>May 2011</start_date>
  <completion_date type="Actual">July 2014</completion_date>
  <primary_completion_date type="Actual">May 2012</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>Double (Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The Primary Outcome Variable Was Probing Depth.</measure>
    <time_frame>6-months</time_frame>
    <description>We measured the probing depth at baseline, 1st, 3rd and 6th months. The changes were evaluated among and between groups.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The Attachment Loss Were Considered as a Secondary Measure.</measure>
    <time_frame>6-months</time_frame>
    <description>Attachment loss were recorded at baseline, 1st, 3rd and 6th months as millimeters. The data were compared among and between groups.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">39</enrollment>
  <condition>Generalized Aggressive Periodontitis</condition>
  <condition>Aggressive Periodontitis</condition>
  <arm_group>
    <arm_group_label>amoxicillin+metronidazole</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>amoxicillin+metronidazole group received a combination of 500 mg of amoxicillin and 500 mg metronidazole three times per day for 7 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>moxifloxacin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The moxifloxacin group received 400 mg moxifloxacin, once in a day for 7 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Amoxicillin</intervention_name>
    <description>500 mg, 3 times per day for 7 days</description>
    <arm_group_label>amoxicillin+metronidazole</arm_group_label>
    <other_name>largopen</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metronidazole</intervention_name>
    <description>500 mg, 3 times per day, for 7 days</description>
    <arm_group_label>amoxicillin+metronidazole</arm_group_label>
    <other_name>flagyl</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Moxifloxacin</intervention_name>
    <description>400 mg, once in a day for 7 days.</description>
    <arm_group_label>moxifloxacin</arm_group_label>
    <other_name>pitoxil</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  The periodontal diagnosis of subjects with GAgP was established on the basis of&#xD;
             clinical and radiographic criteria defined by the 1999 International World Workshop&#xD;
             for a Classification of Periodontal Diseases and Conditions.&#xD;
&#xD;
          -  Patients were included if they were between 18 and 35 years of age and otherwise&#xD;
             healthy.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  if the patients had any known systemic diseases or conditions that can/could influence&#xD;
             the periodontal status (cancer, cardiovascular and respiratory diseases)&#xD;
&#xD;
          -  history of hepatitis or HIV infection,&#xD;
&#xD;
          -  immunosuppressive chemotherapy&#xD;
&#xD;
          -  current pregnancy, planning a pregnancy or lactation&#xD;
&#xD;
          -  requirement for antibiotic prophylaxis&#xD;
&#xD;
          -  oral diseases other than GAgP, ongoing orthodontic therapy&#xD;
&#xD;
          -  a history of antibiotic therapy or periodontal treatment within the preceding six&#xD;
             months.&#xD;
&#xD;
          -  Subjects were excluded if they had known allergies to quinolones or penicillin or&#xD;
             metronidazole&#xD;
&#xD;
          -  Not willing to participate to the study.&#xD;
&#xD;
          -  Not accept to sign written informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>35 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Esra Guzeldemir-Akcakanat</last_name>
    <role>Principal Investigator</role>
    <affiliation>Kocaeli University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Kocaeli University Faculty of Dentistry Department of Periodontology</name>
      <address>
        <city>Kocaeli</city>
        <zip>41190</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Turkey</country>
  </location_countries>
  <reference>
    <citation>Guentsch A, Jentsch H, Pfister W, Hoffmann T, Eick S. Moxifloxacin as an adjunctive antibiotic in the treatment of severe chronic periodontitis. J Periodontol. 2008 Oct;79(10):1894-903. doi: 10.1902/jop.2008.070493.</citation>
    <PMID>18834244</PMID>
  </reference>
  <reference>
    <citation>Sobottka I, Cachovan G, Sturenburg E, Ahlers MO, Laufs R, Platzer U, Mack D. In vitro activity of moxifloxacin against bacteria isolated from odontogenic abscesses. Antimicrob Agents Chemother. 2002 Dec;46(12):4019-21. doi: 10.1128/AAC.46.12.4019-4021.2002.</citation>
    <PMID>12435716</PMID>
  </reference>
  <results_reference>
    <citation>Herrera D, Sanz M, Jepsen S, Needleman I, Roldan S. A systematic review on the effect of systemic antimicrobials as an adjunct to scaling and root planing in periodontitis patients. J Clin Periodontol. 2002;29 Suppl 3:136-59; discussion 160-2. doi: 10.1034/j.1600-051x.29.s3.8.x.</citation>
    <PMID>12787214</PMID>
  </results_reference>
  <results_reference>
    <citation>Mestnik MJ, Feres M, Figueiredo LC, Duarte PM, Lira EA, Faveri M. Short-term benefits of the adjunctive use of metronidazole plus amoxicillin in the microbial profile and in the clinical parameters of subjects with generalized aggressive periodontitis. J Clin Periodontol. 2010 Apr;37(4):353-65. doi: 10.1111/j.1600-051X.2010.01538.x.</citation>
    <PMID>20447259</PMID>
  </results_reference>
  <results_reference>
    <citation>Sgolastra F, Petrucci A, Gatto R, Monaco A. Effectiveness of systemic amoxicillin/metronidazole as an adjunctive therapy to full-mouth scaling and root planing in the treatment of aggressive periodontitis: a systematic review and meta-analysis. J Periodontol. 2012 Jun;83(6):731-43. doi: 10.1902/jop.2011.110432. Epub 2011 Nov 3.</citation>
    <PMID>22050545</PMID>
  </results_reference>
  <results_reference>
    <citation>Herrera D, Alonso B, Leon R, Roldan S, Sanz M. Antimicrobial therapy in periodontitis: the use of systemic antimicrobials against the subgingival biofilm. J Clin Periodontol. 2008 Sep;35(8 Suppl):45-66. doi: 10.1111/j.1600-051X.2008.01260.x.</citation>
    <PMID>18724841</PMID>
  </results_reference>
  <results_reference>
    <citation>Xajigeorgiou C, Sakellari D, Slini T, Baka A, Konstantinidis A. Clinical and microbiological effects of different antimicrobials on generalized aggressive periodontitis. J Clin Periodontol. 2006 Apr;33(4):254-64. doi: 10.1111/j.1600-051X.2006.00905.x.</citation>
    <PMID>16553634</PMID>
  </results_reference>
  <verification_date>February 2018</verification_date>
  <study_first_submitted>August 20, 2014</study_first_submitted>
  <study_first_submitted_qc>August 20, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 22, 2014</study_first_posted>
  <results_first_submitted>June 3, 2015</results_first_submitted>
  <results_first_submitted_qc>February 9, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">November 2, 2018</results_first_posted>
  <last_update_submitted>February 9, 2018</last_update_submitted>
  <last_update_submitted_qc>February 9, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">November 2, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Kocaeli University</investigator_affiliation>
    <investigator_full_name>Esra Guzeldemir-Akcakanat</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>Aggressive periodontitis</keyword>
  <keyword>amoxicillin</keyword>
  <keyword>metronidazole</keyword>
  <keyword>moxifloxacin</keyword>
  <keyword>nonsurgical periodontal debridement.</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Periodontitis</mesh_term>
    <mesh_term>Aggressive Periodontitis</mesh_term>
    <mesh_term>Aggression</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Amoxicillin</mesh_term>
    <mesh_term>Moxifloxacin</mesh_term>
    <mesh_term>Metronidazole</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Amoxicillin+Metronidazole</title>
          <description>amoxicillin+metronidazole group received a combination of 500 mg of amoxicillin and 500 mg metronidazole three times per day for 7 days.&#xD;
Amoxicillin: 500 mg, 3 times per day for 7 days&#xD;
Metronidazole: 500 mg, 3 times per day, for 7 days</description>
        </group>
        <group group_id="P2">
          <title>Moxifloxacin</title>
          <description>The moxifloxacin group received 400 mg moxifloxacin, once in a day for 7 days.&#xD;
Moxifloxacin: 400 mg, once in a day for 7 days.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="19"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
                <participants group_id="P2" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Amoxicillin+Metronidazole</title>
          <description>amoxicillin+metronidazole group received a combination of 500 mg of amoxicillin and 500 mg metronidazole three times per day for 7 days.&#xD;
Amoxicillin: 500 mg, 3 times per day for 7 days&#xD;
Metronidazole: 500 mg, 3 times per day, for 7 days</description>
        </group>
        <group group_id="B2">
          <title>Moxifloxacin</title>
          <description>The moxifloxacin group received 400 mg moxifloxacin, once in a day for 7 days.&#xD;
Moxifloxacin: 400 mg, once in a day for 7 days.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="20"/>
            <count group_id="B2" value="19"/>
            <count group_id="B3" value="39"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age, Customized</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>years (older than 18 years, younger than 35 years)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Turkey</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>The Primary Outcome Variable Was Probing Depth.</title>
        <description>We measured the probing depth at baseline, 1st, 3rd and 6th months. The changes were evaluated among and between groups.</description>
        <time_frame>6-months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Amoxicillin+Metronidazole</title>
            <description>amoxicillin+metronidazole group received a combination of 500 mg of amoxicillin and 500 mg metronidazole three times per day for 7 days.&#xD;
Amoxicillin: 500 mg, 3 times per day for 7 days&#xD;
Metronidazole: 500 mg, 3 times per day, for 7 days</description>
          </group>
          <group group_id="O2">
            <title>Moxifloxacin</title>
            <description>The moxifloxacin group received 400 mg moxifloxacin, once in a day for 7 days.&#xD;
Moxifloxacin: 400 mg, once in a day for 7 days.</description>
          </group>
        </group_list>
        <measure>
          <title>The Primary Outcome Variable Was Probing Depth.</title>
          <description>We measured the probing depth at baseline, 1st, 3rd and 6th months. The changes were evaluated among and between groups.</description>
          <units>mm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.57" spread="1.08"/>
                    <measurement group_id="O2" value="4.18" spread="0.62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>1st month</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.12" spread="0.68"/>
                    <measurement group_id="O2" value="2.91" spread="0.38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>3rd month</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.11" spread="0.6"/>
                    <measurement group_id="O2" value="2.79" spread="0.33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6th month</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.15" spread="0.67"/>
                    <measurement group_id="O2" value="3.01" spread="0.46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.01</p_value>
            <method>Friedman Test</method>
            <method_desc>All rows were compared to eachother</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Attachment Loss Were Considered as a Secondary Measure.</title>
        <description>Attachment loss were recorded at baseline, 1st, 3rd and 6th months as millimeters. The data were compared among and between groups.</description>
        <time_frame>6-months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Amoxicillin+Metronidazole</title>
            <description>amoxicillin+metronidazole group received a combination of 500 mg of amoxicillin and 500 mg metronidazole three times per day for 7 days.&#xD;
Amoxicillin: 500 mg, 3 times per day for 7 days&#xD;
Metronidazole: 500 mg, 3 times per day, for 7 days</description>
          </group>
          <group group_id="O2">
            <title>Moxifloxacin</title>
            <description>The moxifloxacin group received 400 mg moxifloxacin, once in a day for 7 days.&#xD;
Moxifloxacin: 400 mg, once in a day for 7 days.</description>
          </group>
        </group_list>
        <measure>
          <title>The Attachment Loss Were Considered as a Secondary Measure.</title>
          <description>Attachment loss were recorded at baseline, 1st, 3rd and 6th months as millimeters. The data were compared among and between groups.</description>
          <units>mm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.03" spread="1.14"/>
                    <measurement group_id="O2" value="4.94" spread="0.81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>1st month</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.37" spread="0.87"/>
                    <measurement group_id="O2" value="4.14" spread="0.87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>3rd month</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.41" spread="0.93"/>
                    <measurement group_id="O2" value="3.98" spread="0.82"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6th month</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.33" spread="0.94"/>
                    <measurement group_id="O2" value="4.30" spread="0.93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.01</p_value>
            <method>ANOVA</method>
            <method_desc>All rows were compared to eachother</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Amoxicillin+Metronidazole</title>
          <description>amoxicillin+metronidazole group received a combination of 500 mg of amoxicillin and 500 mg metronidazole three times per day for 7 days.&#xD;
Amoxicillin: 500 mg, 3 times per day for 7 days&#xD;
Metronidazole: 500 mg, 3 times per day, for 7 days</description>
        </group>
        <group group_id="E2">
          <title>Moxifloxacin</title>
          <description>The moxifloxacin group received 400 mg moxifloxacin, once in a day for 7 days.&#xD;
Moxifloxacin: 400 mg, once in a day for 7 days.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Chair and Associate Professor of Periodontology</name_or_title>
      <organization>Kocaeli University</organization>
      <phone>+902623442222 ext 5102</phone>
      <email>esragd@yahoo.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02223702
org study id: KOUKAEK5/9
nct id: NCT02223702
lead sponsor: 
has dmc: No
The objective of this randomized clinical study was to evaluate the effect of systemic
      administration of moxifloxacin compared to amoxicillin plus metronidazole combined with
      non-surgical treatment in patients with generalized aggressive periodontitis (GAgP) in
      6-month follow-up.

      A total of 40 systemically healthy patients with GAgP will evaluate in this randomized
      clinical trial. Periodontal parameters (plaque index, gingival index, probing depth, bleeding
      on probing, clinical attachment level) will be recorded at baseline, 1st, 3rd and 6th month.
      Patients will receive either 400 mg moxifloxacin per os once daily or 500 mg metronidazole
      and 500 mg amoxicillin per os three times daily for 7 days consecutively.
The American Academy of Periodontology and the European Federation of Periodontology were
      reported that patients with GAgP may have benefit from adjunctive administration of
      antibiotics. Antibiotics are used as an adjunct to nonsurgical treatment either locally or
      systemically. Systemic antimicrobial agents as adjunct to nonsurgical treatment provide
      additional benefits over mechanical therapy alone in terms of probing depth reduction and
      periodontal attachment gain.

      Amoxicillin is a moderate spectrum, bacteriolytic β-lactam antibiotic, and metronidazole
      which is active against anaerobic bacteria is a nitroimidazole. scaling and root planing
      combination with metronidazole plus amoxicillin therapy was found to be more effective in
      suppressing P. gingivalis and eradication of A. actinomycetemcomitans and preventing
      re-colonization of A. actinomycetemcomitans because of the synergistic effect of this
      combination and their wide spectrum of activity. It was found to be superior to azithromycin,
      doxycycline, and metronidazole in the treatment of GAgP.

      Quinolones were introduced for use in urinary tract infections in the 1970s. Moxiflocaxin is
      a fourth generation fluoroquinolone antibiotic exhibits good tissue penetration and high oral
      bioavailability and has improved activity against Gram- positive, aerobic and anaerobes.
      Moxifloxacin is used in the systemic treatment of respiratory infections, acute sinusitis,
      odontogenic abscesses, osteomyelitis of the mandible and locally in the treatment of
      ophthalmic infections.

      Moxiflocaxin has good activity against putative periodontal pathogens, including
      Porphyromonas gingivalis, Tanneralla forsythia, Prevotella spp, Fusobacterium nucleatum,
      Actinomyces spp, Campylobacter rectus, Peptostreptococcus spp. and Aggregatibacter
      actinomycetemcomitans, located within biofilm or intracellulary. It was shown that A.a.
      strains were highly susceptible to fluoro-quinolones ciprofloxacin and moxifloxacin. Some of
      the adjunctive antibiotics are secreted in saliva in insufficient concentrations to inhibit
      A.a. Moxifloxacin seems to be secreted in saliva at higher levels than in plasma and may also
      concentrate at the site of infection since it penetrates polymorphonuclear granulocytes and
      epithelial cells. Moxifloxacin was found to be superior to clindamycin, metronidazole or
      doxycycline.

      Systemic administration of moxifloxacin as an adjunct to scaling and root planing was found
      to be more effective compared to scaling and root planing alone or scaling and root planing
      in conjunction with doxycycline in the treatment of severe chronic periodontitis. To best our
      knowledge, there is no study that evaluates the effect of moxifloxacin adjunct to scaling and
      root planing in the treatment of GAgP.

      The aim of this single center, randomized clinical study was to evaluate the impact of
      adjunctive systemic moxifloxacin compared to the use of adjunctive systemic amoxicillin and
      metronidazole during full-mouth scaling and root planing on the success of the treatment of
      patients with GAgP with 6-month follow-up. The hypothesis was the use of adjunctive systemic
      moxifloxacin would provide the similar clinical results as adjunct systemic amoxicillin and
      metronidazole during scaling and root planing.

      This study was a single-center, randomized, parallel-design clinical trial with 6 month
      follow-up. It was conducted at Kocaeli University, Faculty of Dentistry, Department of
      Periodontology between 2011-2013. The study protocol was approved by the Ethics Committee of
      the Medical Faculty of Kocaeli University (KOU KAEK 5/9) and was conducted in accordance with
      the Helsinki declaration of 1975, as revised in 2000.

      The GAgP patients were recruited from patients seeking periodontal treatment at Kocaeli
      University, Faculty of Dentistry, Department of Periodontology, Kocaeli, Turkey.
      Approximately, 12.000 patients were screened the dates between June 2011 and September 2012.
      A complete medical, dental, periodontal and radiographic examination was performed. The study
      protocol explained to the patients. From patients who willing to participate to the study,
      written informed consent was obtained and included the study.

      The periodontal diagnosis of subjects with GAgP was established on the basis of clinical and
      radiographic criteria defined by the 1999 International World Workshop for a Classification
      of Periodontal Diseases and Conditions. Patients were included if they were between 18 and 35
      years of age and otherwise healthy. The bone loss estimation was radiographically performed
      in each patient for the assessment of the extent and severity of alveolar bone loss. Medical
      and dental histories were questioned. Subjects were excluded if they had any known systemic
      diseases or conditions that can/could influence the periodontal status (cancer,
      cardiovascular and respiratory diseases), history of hepatitis or HIV infection,
      immunosuppressive chemotherapy, current pregnancy, planning a pregnancy or lactation,
      requirement for antibiotic prophylaxis, oral diseases other than GAgP, ongoing orthodontic
      therapy, a history of antibiotic therapy or periodontal treatment within the preceding six
      months. Subjects were excluded if they had known allergies to quinolones or penicillin or
      metronidazole.

      Periodontal Examination The full-mouth clinical periodontal measurements were recorded at 6
      sites per tooth (mesio-buccal, mid-buccal, disto-buccal, disto-lingual, mid-lingual, and
      mesio-lingual) including plaque index (PI), gingival index (GI), probing depth (PD), bleeding
      on probing (BOP) and clinical attachment level (CAL). CAL was calculated from the
      cement-enamel junction to the base of the periodontal pocket. Williams periodontal probe was
      used for periodontal measurements. All measurements and scaling and root planing were
      performed by the same single calibrated and trained periodontist in a standardized manner.

      Allocation concealment The patients were randomly assigned to one of the study groups. To
      ensure complete masking of allocation, before the recruitment of the patients, forty
      identical, opaque-colored, impermeable plastic bags which include toothbrush, interproximal
      brush, toothpaste and either moxifloxacin or amoxicillin and metronidazole were prepared and
      coded. A code number was given to each subject. Randomization codes were kept separately from
      the clinical evaluation forms by one of the authors until the treatment and follow-up visits
      were completed. The examiner who performed the treatment was unaware of the allocation.

      Prior to treatment, all subjects were gone through motivation sessions for oral hygiene.

      Following to periodontal measurements, full-mouth supragingival scaling using ultrasonic
      scaler and polishing were performed, and a toothbrush, toothpaste and an interproximal
      toothbrush were provided to all subjects. One week later, the patients were examined for
      plaque accumulation and oral hygiene. The patients who cannot maintain proper oral hygiene
      were excluded from the study. Only 39 patients fulfilled the qualification criteria for
      enrollment for the present study.

      Subjects were randomly assigned to receive one of the two treatment groups. Moxifloxacin
      group received scaling and root planing and an adjunctive systemic antibiotic, 400 mg
      moxifloxacin, once in a day for 7 days and amoxicillin and metronidazole group received a
      combination of 500 mg of amoxicillin and 500 mg metronidazole three times per day for 7 days.
      The subjects were instructed to take first dose of the antibiotics in the morning of the
      first session since the microorganisms are organized on the root surface and protected from
      antimicrobial agents. Scaling and root planing were performed on 2 consecutive days in 24
      hours under the local anesthesia. On each day, scaling and root planing were performed in 2
      quadrants using ultrasonic scalers and manual instruments . The endpoint of scaling and root
      planing was a tactile smooth root surface.

      The subjects were insistently informed about the intake of the antibiotics properly, and they
      asked to inform the researches if they needed to take another antibiotics or
      anti-inflammatory agents for another reason during and following the study for 6 months.

      Patients used a 0.2% chlorhexidine digluconate rinse twice a day for a month and brushed
      their teeth by tooth brushes and interproximal tooth brushes twice a day. Patients asked to
      report any adverse events and side effects of the antimicrobial agents as soon as possible.

      Subjects were monitored one week after the second scaling and root planing session. At this
      session, antibiotic intake, adverse events and side effects were questioned; oral hygiene and
      plaque accumulation were controlled. Subjects were screened at 1, 3 and 6 months after
      completion of nonsurgical treatment. During these sessions, clinical periodontal parameters,
      any medical history change, especially, whether antibiotic therapy had been prescribed for
      any reason was recorded. At the end of these sessions, supragingival scaling was performed,
      if needed.

      The present study was conducted within in the same clinic, and the patients were taken to the
      same dental chair and treated with a same experienced periodontist for to discard
      discrepancies and to provide standardized and controlled environment.

      Sample size calculation

      The primary outcome variable was probing depth changes. The sample size was calculated based
      on previous information from a study conducted in our department, using data relative to the
      mean difference and standard deviation (SD) between the experimental periods for the probing
      depth parameters.57 Considering a mean probing depth difference of 1.3 mm between evaluation
      periods, it was estimated that 13 patients for each group would be necessary to provide 95%
      power (0.54 SD, α error of 0.05, and β error of 0.2).58 However, we aimed to recruit 20
      patients to each group if we lose to follow the patients during the study.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: Double (Investigator, Outcomes Assessor)
measure: The Primary Outcome Variable Was Probing Depth.
time frame: 6-months
description: We measured the probing depth at baseline, 1st, 3rd and 6th months. The changes were evaluated among and between groups.
measure: The Attachment Loss Were Considered as a Secondary Measure.
time frame: 6-months
description: Attachment loss were recorded at baseline, 1st, 3rd and 6th months as millimeters. The data were compared among and between groups.
arm group label: amoxicillin+metronidazole
arm group type: Active Comparator
description: amoxicillin+metronidazole group received a combination of 500 mg of amoxicillin and 500 mg metronidazole three times per day for 7 days.
arm group label: moxifloxacin
arm group type: Experimental
description: The moxifloxacin group received 400 mg moxifloxacin, once in a day for 7 days.
intervention type: Drug
intervention name: Amoxicillin
description: 500 mg, 3 times per day for 7 days
arm group label: amoxicillin+metronidazole
other name: largopen
intervention type: Drug
intervention name: Metronidazole
description: 500 mg, 3 times per day, for 7 days
arm group label: amoxicillin+metronidazole
other name: flagyl
intervention type: Drug
intervention name: Moxifloxacin
description: 400 mg, once in a day for 7 days.
arm group label: moxifloxacin
other name: pitoxil
criteria: 
gender: All
minimum age: 18 Years
maximum age: 35 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Esra Guzeldemir-Akcakanat
role: Principal Investigator
affiliation: Kocaeli University
facility: 
country: Turkey
citation: Guentsch A, Jentsch H, Pfister W, Hoffmann T, Eick S. Moxifloxacin as an adjunctive antibiotic in the treatment of severe chronic periodontitis. J Periodontol. 2008 Oct;79(10):1894-903. doi: 10.1902/jop.2008.070493.
PMID: 18834244
citation: Sobottka I, Cachovan G, Sturenburg E, Ahlers MO, Laufs R, Platzer U, Mack D. In vitro activity of moxifloxacin against bacteria isolated from odontogenic abscesses. Antimicrob Agents Chemother. 2002 Dec;46(12):4019-21. doi: 10.1128/AAC.46.12.4019-4021.2002.
PMID: 12435716
citation: Herrera D, Sanz M, Jepsen S, Needleman I, Roldan S. A systematic review on the effect of systemic antimicrobials as an adjunct to scaling and root planing in periodontitis patients. J Clin Periodontol. 2002;29 Suppl 3:136-59; discussion 160-2. doi: 10.1034/j.1600-051x.29.s3.8.x.
PMID: 12787214
citation: Mestnik MJ, Feres M, Figueiredo LC, Duarte PM, Lira EA, Faveri M. Short-term benefits of the adjunctive use of metronidazole plus amoxicillin in the microbial profile and in the clinical parameters of subjects with generalized aggressive periodontitis. J Clin Periodontol. 2010 Apr;37(4):353-65. doi: 10.1111/j.1600-051X.2010.01538.x.
PMID: 20447259
citation: Sgolastra F, Petrucci A, Gatto R, Monaco A. Effectiveness of systemic amoxicillin/metronidazole as an adjunctive therapy to full-mouth scaling and root planing in the treatment of aggressive periodontitis: a systematic review and meta-analysis. J Periodontol. 2012 Jun;83(6):731-43. doi: 10.1902/jop.2011.110432. Epub 2011 Nov 3.
PMID: 22050545
citation: Herrera D, Alonso B, Leon R, Roldan S, Sanz M. Antimicrobial therapy in periodontitis: the use of systemic antimicrobials against the subgingival biofilm. J Clin Periodontol. 2008 Sep;35(8 Suppl):45-66. doi: 10.1111/j.1600-051X.2008.01260.x.
PMID: 18724841
citation: Xajigeorgiou C, Sakellari D, Slini T, Baka A, Konstantinidis A. Clinical and microbiological effects of different antimicrobials on generalized aggressive periodontitis. J Clin Periodontol. 2006 Apr;33(4):254-64. doi: 10.1111/j.1600-051X.2006.00905.x.
PMID: 16553634
responsible party type: Principal Investigator
investigator affiliation: Kocaeli University
investigator full name: Esra Guzeldemir-Akcakanat
investigator title: Associate Professor
mesh term: Periodontitis
mesh term: Aggressive Periodontitis
mesh term: Aggression
mesh term: Amoxicillin
mesh term: Moxifloxacin
mesh term: Metronidazole
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 