<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/NCT03001752</url>
  </required_header>
  <id_info>
    <org_study_id>4987</org_study_id>
    <nct_id>NCT03001752</nct_id>
  </id_info>
  <brief_title>Immediate Implants Inserted Through Open Flap, Open Flap and Bone Grafting and Flapless Techniques</brief_title>
  <acronym>ETPEI-RCT</acronym>
  <official_title>Evaluation of Morphological and Dimensional Alveolar Bone Changes Around Post-extraction Implants in an Open Flap, Open Flap and Grafting and Flapless Technique. A Clinical Randomized Controlled Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Bari</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Bari</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a three-armed randomized controlled clinical trial aiming the estimation of&#xD;
      dimensional alveolar bone changes after insertion of post-extraction implants through 3&#xD;
      different surgical techniques: open flap, open flap and grafting, flapless.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background and Objectives A recent systematic review investigating dimensional alveolar bone&#xD;
      changes after insertion of post-extraction implants reported that there is a lack of&#xD;
      randomized controlled trials that would serve as a scientific base for building clinical&#xD;
      guidelines on alveolar site treatment after insertion of post-extraction implants. Different&#xD;
      studies suggest that insertion of post-extraction implants should be performed after fully&#xD;
      elevating a flap and inserting bone graft in the residual space between the implant surface&#xD;
      and the alveolar socket. Other investigations report insignificant differences between open&#xD;
      flap and flapless approaches, whereas the insertion of bone grafts remains controversial.&#xD;
&#xD;
      The present study is a three-armed randomized clinical controlled trial conducted with the&#xD;
      following objectives:&#xD;
&#xD;
        1. Evaluation of morphological and alveolar bone level differences (marginal bone loss) on&#xD;
           post-extraction implants inserted with the following techniques: 1) open flap surgery&#xD;
           alone; 2) open flap surgery and bone grafting; 3) flapless.&#xD;
&#xD;
        2. Estimation of effectiveness of the three surgical techniques through measurement of&#xD;
           secondary outcomes such as intra-operatory and post-operatory complications, pain and&#xD;
           discomfort, time and costs.&#xD;
&#xD;
      Materials and Methods&#xD;
&#xD;
        -  This is a three-armed randomized controlled clinical trial where each arm will belong to&#xD;
           one of the treatments: 1) open flap surgery alone; 2) open flap surgery and bone&#xD;
           grafting; 3) flapless.&#xD;
&#xD;
        -  The randomizing sequence will be generated from a computer program (STATA 13) by a&#xD;
           statistician who will also conduct blind statistical analysis of results.&#xD;
&#xD;
        -  All patients will be recruited prior to trial commencement. They will be extensively&#xD;
           informed regarding the intervention and will sign a treatment consent.&#xD;
&#xD;
        -  Patients will be recruited according to the following inclusion criteria: absence of any&#xD;
           systemic disease that might compromise implant integration or wound healing, appropriate&#xD;
           periodontal health (measured through periodontal indexes), presence of premolars with&#xD;
           indications of extractions, presence of adjacent teeth, absence of fenestrations,&#xD;
           presence of vestibular alveolar wall with a minimum of 0.5mm of thickness. Patients who&#xD;
           have undergone CT scanning in the past 5 years and heavy smokers (more than 20&#xD;
           cigarettes per day) will not be included in the study.&#xD;
&#xD;
        -  Calculation of sample size has already been performed by an experienced statistician,&#xD;
           accounting for a minimal predicted difference between groups of 1mm (SD 0.75mm) of&#xD;
           marginal bone loss, alpha error of 0.05 and 90% of power. Based on these calculations, a&#xD;
           total of 45 patients will be included in the study.&#xD;
&#xD;
        -  Interventions will be performed in accordance with ethical standards as suggested by the&#xD;
           Helsinki Declaration (1975). Approval of Ethical Committee of the University of Bari has&#xD;
           already been obtained (reg.nr. 4987).&#xD;
&#xD;
        -  All surgical interventions will be performed by the same experienced surgeon who will be&#xD;
           informed of the type of intervention after tooth extraction (allocation concealment&#xD;
           through dark sealed envelopes).&#xD;
&#xD;
        -  The primary outcome is marginal bone loss (MBL) and alveolar bone dimensional changes&#xD;
           measured through CT Cone Beam performed immediately after implant insertion and 6 months&#xD;
           after. Secondary outcomes are intra-and post-operative complications, pain and&#xD;
           discomfort, time and costs.&#xD;
&#xD;
        -  Outcomes will be measured by another clinician blinded in terms of treatment allocation.&#xD;
&#xD;
        -  Statistical analysis will be performed by an independent statistician. Statistical tests&#xD;
           will include: One-way Anova, Bonferroni tests and several linear and logistic&#xD;
           regressions in order to estimate potential predictive variables. Statistical&#xD;
           significance will be set at .05.&#xD;
&#xD;
        -  Interruption of study will be considered in the following situations: 1.preliminary&#xD;
           observation of highly significant difference between techniques indicating one technique&#xD;
           highly superior; 2. big number of lost to follow-up (bigger than that considered during&#xD;
           sample size calculation)&#xD;
&#xD;
        -  Patients will be excluded from the study in the following cases: missing follow-up&#xD;
           hygiene controls at 1 and 3 months post-intervention, missing 6 months follow-up&#xD;
           control, poor cooperation in terms of domestic oral hygiene (periodontal indexes&#xD;
           measured), income of systemic or local diseases that might compromise outcomes.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 2017</start_date>
  <completion_date type="Actual">November 2018</completion_date>
  <primary_completion_date type="Actual">August 2018</primary_completion_date>
  <phase>N/A</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>Triple (Participant, Investigator, Outcomes Assessor)</masking>
    <masking_description>The care provider could not be blinded because of the nature of the treatment. The patient was blinded and the investigator and outcome assessor as well (using a code to identify teeth and patients).</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Marginal Bone Loss measured through CT Cone Beam</measure>
    <time_frame>6 months</time_frame>
    <description>Difference of marginal bone level measured immediately after treatment and 6 months after on two repeated (immediately after and 6 months after implant insertion) CT Cone Beam</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Alveolar Bone Dimensional Reduction assessed through CT Cone Beam</measure>
    <time_frame>6 months</time_frame>
    <description>Three-dimensional Alveolar Bone Reduction (horizontal and vertical) will be measured on two repeated (immediately after and 6 months after implant insertion) on CT Cone Beam, having as reference points the implant platform and the implant apex.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pain and Discomfort measured through questionaire</measure>
    <time_frame>1 Week</time_frame>
    <description>Pain and discomfort experienced by the patient after the surgery, measured through a VAS scale on a questionaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intra-operatory or post-operatory complications assessed through intra-operatory observation and post-intervention check-ups.</measure>
    <time_frame>6 months</time_frame>
    <description>Intra-operatory or post-operatory intervention-related adverse events such as excessive bleeding, swallowing, hematoma will be recorded for each patient.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time needed to perform surgical intervention</measure>
    <time_frame>1-2 hours</time_frame>
    <description>Time needed to perform surgical intervention (immediately after tooth extraction until finishing of surgical procedure) will be recorded for each intervention.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">45</enrollment>
  <condition>Isolated Premolar Edentulous Site</condition>
  <arm_group>
    <arm_group_label>Open flap immediate implant</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Open flap immediate implant insertion, without bone grafting</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Open flap immediate implant and bone grafting</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Open flap immediate implant insertion and bone grafting</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Flapless immediate implant</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Immediate implant insertion without opening flap of inserting bone grafting</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Open flap immediate implant</intervention_name>
    <description>Post-extraction implants will be inserted through open flap, without bone grafting</description>
    <arm_group_label>Open flap immediate implant</arm_group_label>
    <other_name>Dental implant</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Open flap immediate implant and bone grafting</intervention_name>
    <description>Post-extraction implants will be inserted through open flap, adding bone grafting</description>
    <arm_group_label>Open flap immediate implant and bone grafting</arm_group_label>
    <other_name>Dental implant, bone grafting</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Flapless immediate implant</intervention_name>
    <description>Post-extraction implants will be inserted without elevating flap or inserting bone grafting</description>
    <arm_group_label>Flapless immediate implant</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  absence of any systemic disease that might compromise implant integration or wound&#xD;
             healing&#xD;
&#xD;
          -  appropriate periodontal health (measured through periodontal indexes)&#xD;
&#xD;
          -  presence of premolars with indications of extractions, presence of adjacent teeth&#xD;
&#xD;
          -  absence of fenestrations&#xD;
&#xD;
          -  presence of vestibular alveolar wall with a minimum of 0.5mm of thickness&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  patients who have undergone CT scanning in the past 5 years&#xD;
&#xD;
          -  heavy smokers (more than 20 cigarettes per day)&#xD;
&#xD;
          -  patients not showing up at 1 and 3 months hygiene sessions&#xD;
&#xD;
          -  patients not showing up at 6 months follow-up&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <results_reference>
    <citation>Lee CT, Chiu TS, Chuang SK, Tarnow D, Stoupel J. Alterations of the bone dimension following immediate implant placement into extraction socket: systematic review and meta-analysis. J Clin Periodontol. 2014 Sep;41(9):914-26. doi: 10.1111/jcpe.12276. Epub 2014 Jul 23.</citation>
    <PMID>24894299</PMID>
  </results_reference>
  <results_reference>
    <citation>Tarnow DP, Chu SJ. Human histologic verification of osseointegration of an immediate implant placed into a fresh extraction socket with excessive gap distance without primary flap closure, graft, or membrane: a case report. Int J Periodontics Restorative Dent. 2011 Sep-Oct;31(5):515-21.</citation>
    <PMID>21845246</PMID>
  </results_reference>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>December 16, 2016</study_first_submitted>
  <study_first_submitted_qc>December 22, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 23, 2016</study_first_posted>
  <last_update_submitted>January 15, 2019</last_update_submitted>
  <last_update_submitted_qc>January 15, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 17, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Bari</investigator_affiliation>
    <investigator_full_name>Felice Roberto Grassi</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>post-extraction dental implant</keyword>
  <keyword>immediate dental implant</keyword>
  <keyword>open flap</keyword>
  <keyword>flapless</keyword>
  <keyword>bone grafting</keyword>
  <keyword>CT Cone Beam</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mouth, Edentulous</mesh_term>
  </condition_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/NCT03001752
org study id: 4987
nct id: NCT03001752
lead sponsor: 
has dmc: Yes
This is a three-armed randomized controlled clinical trial aiming the estimation of
      dimensional alveolar bone changes after insertion of post-extraction implants through 3
      different surgical techniques: open flap, open flap and grafting, flapless.
Background and Objectives A recent systematic review investigating dimensional alveolar bone
      changes after insertion of post-extraction implants reported that there is a lack of
      randomized controlled trials that would serve as a scientific base for building clinical
      guidelines on alveolar site treatment after insertion of post-extraction implants. Different
      studies suggest that insertion of post-extraction implants should be performed after fully
      elevating a flap and inserting bone graft in the residual space between the implant surface
      and the alveolar socket. Other investigations report insignificant differences between open
      flap and flapless approaches, whereas the insertion of bone grafts remains controversial.

      The present study is a three-armed randomized clinical controlled trial conducted with the
      following objectives:

        1. Evaluation of morphological and alveolar bone level differences (marginal bone loss) on
           post-extraction implants inserted with the following techniques: 1) open flap surgery
           alone; 2) open flap surgery and bone grafting; 3) flapless.

        2. Estimation of effectiveness of the three surgical techniques through measurement of
           secondary outcomes such as intra-operatory and post-operatory complications, pain and
           discomfort, time and costs.

      Materials and Methods

        -  This is a three-armed randomized controlled clinical trial where each arm will belong to
           one of the treatments: 1) open flap surgery alone; 2) open flap surgery and bone
           grafting; 3) flapless.

        -  The randomizing sequence will be generated from a computer program (STATA 13) by a
           statistician who will also conduct blind statistical analysis of results.

        -  All patients will be recruited prior to trial commencement. They will be extensively
           informed regarding the intervention and will sign a treatment consent.

        -  Patients will be recruited according to the following inclusion criteria: absence of any
           systemic disease that might compromise implant integration or wound healing, appropriate
           periodontal health (measured through periodontal indexes), presence of premolars with
           indications of extractions, presence of adjacent teeth, absence of fenestrations,
           presence of vestibular alveolar wall with a minimum of 0.5mm of thickness. Patients who
           have undergone CT scanning in the past 5 years and heavy smokers (more than 20
           cigarettes per day) will not be included in the study.

        -  Calculation of sample size has already been performed by an experienced statistician,
           accounting for a minimal predicted difference between groups of 1mm (SD 0.75mm) of
           marginal bone loss, alpha error of 0.05 and 90% of power. Based on these calculations, a
           total of 45 patients will be included in the study.

        -  Interventions will be performed in accordance with ethical standards as suggested by the
           Helsinki Declaration (1975). Approval of Ethical Committee of the University of Bari has
           already been obtained (reg.nr. 4987).

        -  All surgical interventions will be performed by the same experienced surgeon who will be
           informed of the type of intervention after tooth extraction (allocation concealment
           through dark sealed envelopes).

        -  The primary outcome is marginal bone loss (MBL) and alveolar bone dimensional changes
           measured through CT Cone Beam performed immediately after implant insertion and 6 months
           after. Secondary outcomes are intra-and post-operative complications, pain and
           discomfort, time and costs.

        -  Outcomes will be measured by another clinician blinded in terms of treatment allocation.

        -  Statistical analysis will be performed by an independent statistician. Statistical tests
           will include: One-way Anova, Bonferroni tests and several linear and logistic
           regressions in order to estimate potential predictive variables. Statistical
           significance will be set at .05.

        -  Interruption of study will be considered in the following situations: 1.preliminary
           observation of highly significant difference between techniques indicating one technique
           highly superior; 2. big number of lost to follow-up (bigger than that considered during
           sample size calculation)

        -  Patients will be excluded from the study in the following cases: missing follow-up
           hygiene controls at 1 and 3 months post-intervention, missing 6 months follow-up
           control, poor cooperation in terms of domestic oral hygiene (periodontal indexes
           measured), income of systemic or local diseases that might compromise outcomes.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
masking description: The care provider could not be blinded because of the nature of the treatment. The patient was blinded and the investigator and outcome assessor as well (using a code to identify teeth and patients).
measure: Marginal Bone Loss measured through CT Cone Beam
time frame: 6 months
description: Difference of marginal bone level measured immediately after treatment and 6 months after on two repeated (immediately after and 6 months after implant insertion) CT Cone Beam
measure: Alveolar Bone Dimensional Reduction assessed through CT Cone Beam
time frame: 6 months
description: Three-dimensional Alveolar Bone Reduction (horizontal and vertical) will be measured on two repeated (immediately after and 6 months after implant insertion) on CT Cone Beam, having as reference points the implant platform and the implant apex.
measure: Pain and Discomfort measured through questionaire
time frame: 1 Week
description: Pain and discomfort experienced by the patient after the surgery, measured through a VAS scale on a questionaire
measure: Intra-operatory or post-operatory complications assessed through intra-operatory observation and post-intervention check-ups.
time frame: 6 months
description: Intra-operatory or post-operatory intervention-related adverse events such as excessive bleeding, swallowing, hematoma will be recorded for each patient.
measure: Time needed to perform surgical intervention
time frame: 1-2 hours
description: Time needed to perform surgical intervention (immediately after tooth extraction until finishing of surgical procedure) will be recorded for each intervention.
arm group label: Open flap immediate implant
arm group type: Active Comparator
description: Open flap immediate implant insertion, without bone grafting
arm group label: Open flap immediate implant and bone grafting
arm group type: Active Comparator
description: Open flap immediate implant insertion and bone grafting
arm group label: Flapless immediate implant
arm group type: Active Comparator
description: Immediate implant insertion without opening flap of inserting bone grafting
intervention type: Device
intervention name: Open flap immediate implant
description: Post-extraction implants will be inserted through open flap, without bone grafting
arm group label: Open flap immediate implant
other name: Dental implant
intervention type: Device
intervention name: Open flap immediate implant and bone grafting
description: Post-extraction implants will be inserted through open flap, adding bone grafting
arm group label: Open flap immediate implant and bone grafting
other name: Dental implant, bone grafting
intervention type: Device
intervention name: Flapless immediate implant
description: Post-extraction implants will be inserted without elevating flap or inserting bone grafting
arm group label: Flapless immediate implant
criteria: 
gender: All
minimum age: 20 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
citation: Lee CT, Chiu TS, Chuang SK, Tarnow D, Stoupel J. Alterations of the bone dimension following immediate implant placement into extraction socket: systematic review and meta-analysis. J Clin Periodontol. 2014 Sep;41(9):914-26. doi: 10.1111/jcpe.12276. Epub 2014 Jul 23.
PMID: 24894299
citation: Tarnow DP, Chu SJ. Human histologic verification of osseointegration of an immediate implant placed into a fresh extraction socket with excessive gap distance without primary flap closure, graft, or membrane: a case report. Int J Periodontics Restorative Dent. 2011 Sep-Oct;31(5):515-21.
PMID: 21845246
responsible party type: Principal Investigator
investigator affiliation: University of Bari
investigator full name: Felice Roberto Grassi
investigator title: Professor
mesh term: Mouth, Edentulous