<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/NCT02185209</url>
  </required_header>
  <id_info>
    <org_study_id>PERI-IMPL</org_study_id>
    <nct_id>NCT02185209</nct_id>
  </id_info>
  <brief_title>Surgical Treatment of Peri-implantitis With and Without Systemically Adjunctive Antibiotics</brief_title>
  <official_title>Surgical Treatment of Peri-implantitis With and Without Systemically Adjunctive Antibiotics A Prospective, Double Blind, Randomized, Three Armed, Parallel, Placebo Controlled Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Margareta Hultin</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Karolinska Institutet</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to investigate if the use of systemic adjunctive antibiotics in&#xD;
      the treatment of periimplantitis is needed.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will give the opportunity to draw scientifically based conclusions on the&#xD;
      recommendations of the use of adjunctive systemic antibiotics in the treatment of&#xD;
      peri-implantitis. This study will also be able to determine the ecological impact on the&#xD;
      oropharyngeal and intestinal microflora between different antibiotic treatments. The lack of&#xD;
      knowledge in this area has been highlighted by the Food and Drug Administration and The&#xD;
      Swedish Council on Health Technology Assessment (SBU)&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>March 2015</start_date>
  <completion_date type="Actual">May 27, 2022</completion_date>
  <primary_completion_date type="Actual">May 27, 2022</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>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Probing pocket depth change and bone level stability</measure>
    <time_frame>0,6 and 12 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change of clinical soft tissue inflammation, bleeding on probing (BOP)</measure>
    <time_frame>0, post operative 12 month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Soft tissue recession (REC) and clinical attachment level gain (CAL)</measure>
    <time_frame>0,6 and 12 month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>• Quantitative and qualitative change in levels of the peri-implant periopathogenic microflora</measure>
    <time_frame>0,6 and 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>• Susceptibility changes of the oral and intestinal microflora to amoxicillin, metronidazole and penicillin.</measure>
    <time_frame>0,6 and 12 month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quantitative and qualitative changes in the oral and intestinal microflora</measure>
    <time_frame>0,6 and 12 month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of amoxicillin, metronidazole and PcV in saliva and feces</measure>
    <time_frame>0, 6 and 12 month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>• Follow-up of adverse events related or unrelated to the investigated medical products</measure>
    <time_frame>0,6, and 12 month</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">77</enrollment>
  <condition>Periodontal Diseases</condition>
  <condition>Periimplantitis</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with periimplantitis undergoing surgical treatment with will receive placebo three times daily (TID)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>amoxicillin + metronidazole</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients with periimplantitis undergoing surgical treatment with amoxicillin (500 mg TID) + metronidazole (400 mg TID) for 7 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>phenoxymetylpencillin + metronidazol</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients with periimplantitis undergoing surgical treatment with phenoxymetylpencillin, (800mg×2 TID) + metronidazol (400 mg TID) for 7 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Place capsule to mimic antibiotics</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Amoxicillin Sandoz</intervention_name>
    <description>Tablet 500 mg amoxicillin Sandoz three times a day</description>
    <arm_group_label>amoxicillin + metronidazole</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metronidazole Sanofi</intervention_name>
    <description>400 mg metronidazole Sanofi administered three times a day (TID)</description>
    <arm_group_label>amoxicillin + metronidazole</arm_group_label>
    <arm_group_label>phenoxymetylpencillin + metronidazol</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Phenoxymethylpenicillin Meda</intervention_name>
    <description>1600 mg phenoxymethylpenicillin Meda, three time a day (TID)</description>
    <arm_group_label>phenoxymetylpencillin + metronidazol</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female ≥18-65 year&#xD;
&#xD;
          2. Patients who has been referred by a general dentist to a specialist clinic in&#xD;
             periodontology for treatment of peri-implantitis.&#xD;
&#xD;
          3. Having sign of peri-implantitis around at least one osseointegrated dental implant&#xD;
             that has been in function for ≥ one year&#xD;
&#xD;
          4. Peri-implantitis is diagnosed when; PPD of ≥ 6mm can be found at a dental implant in&#xD;
             association with BOP and/or suppuration together with the loss of marginal alveolar&#xD;
             bone of more than 2 mm detected on intraoral radiographs (giving radiographic exposure&#xD;
             of at least ≥ 3 fixture threads).&#xD;
&#xD;
          5. Partially or completely edentulous subjects with healthy or treated periodontal&#xD;
             conditions enrolled in a regular supportive program.&#xD;
&#xD;
          6. Full-Mouth Plaque Score (FMPS) ≤ 25&#xD;
&#xD;
          7. Signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Known allergy to amoxicillin, penicillin (PcV), metronidazole or betalactamic&#xD;
&#xD;
          2. Contraindication for dental surgical treatment (i.e. immunocompromised, uncontrolled&#xD;
             DM (B-GHb-A1C 8-9 %, 64-75 mmol/mol), osteoporosis, I.V bisphosphonate treatment due&#xD;
             to malignancy, pregnant and lactating women).&#xD;
&#xD;
          3. Incapability to perform basal oral hygiene measures due to physical or mental&#xD;
             disorders.&#xD;
&#xD;
          4. Received systemic antimicrobial therapy in the past three months.&#xD;
&#xD;
          5. Currently on allopurinol, digoxin, disulfiram, lithium, busulfan, 5-fluorouracil,&#xD;
             methotrexate, phenytoin, cyclosporine and warfarin.&#xD;
&#xD;
          6. Known severe chronic peripheral or central disease of the nervous system&#xD;
&#xD;
          7. Known alcohol abuse&#xD;
&#xD;
          8. Known hepatic encephalopathy&#xD;
&#xD;
          9. Known lactose intolerance, galactose intolerance&#xD;
&#xD;
         10. Untreated periodontal condition.&#xD;
&#xD;
         11. Implant showing sign of mobility.&#xD;
&#xD;
         12. Implants with bone loss exceeding 2/3 of the length of the implant or implants with&#xD;
             bone loss beyond any transverse openings in hollow implants.&#xD;
&#xD;
         13. Any medical condition or on any concomitant medication that, in the opinion of the&#xD;
             investigator, might interfere with the evaluation of the study objectives or&#xD;
             jeopardize patient safety&#xD;
&#xD;
        Patients with xerostomia or having slow bowel motion will be excluded from the group of&#xD;
        patients providing salivary and fecal samples.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Margareta Hultin, DDSass. prof</last_name>
    <role>Study Chair</role>
    <affiliation>Karolinska Institute, Dental medicine</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Bodil Lund, DDSass.prof</last_name>
    <role>Study Director</role>
    <affiliation>Karolinska Institute, Dental Medicine</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Dalia Kahlil, DDS, PhDstud</last_name>
    <role>Principal Investigator</role>
    <affiliation>Karolinska Institute, Dental Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Folktandvården Skanstull</name>
      <address>
        <city>Stockholm</city>
        <zip>SE-118 62</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Folktandvården Kaniken</name>
      <address>
        <city>Uppsala</city>
        <zip>SE 753 09</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>June 23, 2014</study_first_submitted>
  <study_first_submitted_qc>July 6, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 9, 2014</study_first_posted>
  <last_update_submitted>August 17, 2022</last_update_submitted>
  <last_update_submitted_qc>August 17, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 18, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Karolinska Institutet</investigator_affiliation>
    <investigator_full_name>Margareta Hultin</investigator_full_name>
    <investigator_title>DDS</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Periodontal Diseases</mesh_term>
    <mesh_term>Peri-Implantitis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Amoxicillin</mesh_term>
    <mesh_term>Metronidazole</mesh_term>
    <mesh_term>Penicillin V</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT02185209
org study id: PERI-IMPL
nct id: NCT02185209
lead sponsor: 
has dmc: No
The purpose of this study is to investigate if the use of systemic adjunctive antibiotics in
      the treatment of periimplantitis is needed.
This study will give the opportunity to draw scientifically based conclusions on the
      recommendations of the use of adjunctive systemic antibiotics in the treatment of
      peri-implantitis. This study will also be able to determine the ecological impact on the
      oropharyngeal and intestinal microflora between different antibiotic treatments. The lack of
      knowledge in this area has been highlighted by the Food and Drug Administration and The
      Swedish Council on Health Technology Assessment (SBU)
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Probing pocket depth change and bone level stability
time frame: 0,6 and 12 months
measure: Change of clinical soft tissue inflammation, bleeding on probing (BOP)
time frame: 0, post operative 12 month
measure: Soft tissue recession (REC) and clinical attachment level gain (CAL)
time frame: 0,6 and 12 month
measure: • Quantitative and qualitative change in levels of the peri-implant periopathogenic microflora
time frame: 0,6 and 12 months
measure: • Susceptibility changes of the oral and intestinal microflora to amoxicillin, metronidazole and penicillin.
time frame: 0,6 and 12 month
measure: Quantitative and qualitative changes in the oral and intestinal microflora
time frame: 0,6 and 12 month
measure: Concentration of amoxicillin, metronidazole and PcV in saliva and feces
time frame: 0, 6 and 12 month
measure: • Follow-up of adverse events related or unrelated to the investigated medical products
time frame: 0,6, and 12 month
arm group label: Placebo
arm group type: Experimental
description: Patients with periimplantitis undergoing surgical treatment with will receive placebo three times daily (TID)
arm group label: amoxicillin + metronidazole
arm group type: Active Comparator
description: Patients with periimplantitis undergoing surgical treatment with amoxicillin (500 mg TID) + metronidazole (400 mg TID) for 7 days
arm group label: phenoxymetylpencillin + metronidazol
arm group type: Active Comparator
description: Patients with periimplantitis undergoing surgical treatment with phenoxymetylpencillin, (800mg×2 TID) + metronidazol (400 mg TID) for 7 days
intervention type: Drug
intervention name: Placebo
description: Place capsule to mimic antibiotics
arm group label: Placebo
intervention type: Drug
intervention name: Amoxicillin Sandoz
description: Tablet 500 mg amoxicillin Sandoz three times a day
arm group label: amoxicillin + metronidazole
intervention type: Drug
intervention name: Metronidazole Sanofi
description: 400 mg metronidazole Sanofi administered three times a day (TID)
arm group label: amoxicillin + metronidazole
arm group label: phenoxymetylpencillin + metronidazol
intervention type: Drug
intervention name: Phenoxymethylpenicillin Meda
description: 1600 mg phenoxymethylpenicillin Meda, three time a day (TID)
arm group label: phenoxymetylpencillin + metronidazol
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Margareta Hultin, DDSass. prof
role: Study Chair
affiliation: Karolinska Institute, Dental medicine
last name: Bodil Lund, DDSass.prof
role: Study Director
affiliation: Karolinska Institute, Dental Medicine
last name: Dalia Kahlil, DDS, PhDstud
role: Principal Investigator
affiliation: Karolinska Institute, Dental Medicine
facility: 
facility: 
country: Sweden
responsible party type: Sponsor-Investigator
investigator affiliation: Karolinska Institutet
investigator full name: Margareta Hultin
investigator title: DDS
mesh term: Periodontal Diseases
mesh term: Peri-Implantitis
mesh term: Amoxicillin
mesh term: Metronidazole
mesh term: Penicillin V