xml: <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/NCT06029322</url>
    </required_header>
    <id_info>
      <org_study_id>1-15082023</org_study_id>
      <nct_id>NCT06029322</nct_id>
    </id_info>
    <brief_title>Collagen Matrix Versus Collagen Membrane as Socket Seal in ARP</brief_title>
    <official_title>A Randomized Controlled Trial Comparing Collagen Matrix to Collagen Membrane as Socket Seal in Alveolar Ridge Preservation</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University Ghent</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>University Ghent</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Patients in need of extraction of two teeth in combination with alveolar ridge preservation&#xD;
        will be invited to participate in intra-subject RCT on ARP. Prior to surgery, a small-field&#xD;
        low-dose CBCT is taken.&#xD;
  &#xD;
        18 patients will be included, each contributing 1 surgical site to each treatment arm.&#xD;
  &#xD;
        Since this study is a intra-subject RCT randomization of the surgical site will be performed&#xD;
        just after ARP by a coin flip. Randomization is concealed for the evaluating examiner and&#xD;
        statistician.&#xD;
  &#xD;
        After ARP the collagen matrix or collagen membrane is used to seal the coronal aspect of the&#xD;
        extraction socket.&#xD;
  &#xD;
        Soft tissue thickness in centre of the site will be determined using CBCT. Secondary outcomes&#xD;
        include: Wound dimensions, socket wound healing score, changes in bone and soft tissue&#xD;
        dimensions and changes in buccal soft tissue profile&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The primary study objective is to compare soft tissue thickness in the centre of the site&#xD;
        between collagen matrix and collagen membrane at 4 months following ARP.&#xD;
  &#xD;
        Secondary study outcomes relate to the same comparison and include the following variables:&#xD;
        wound reduction after 7 days and 21 days, socket wound healing score after 7 days, 21 days&#xD;
        and 4 months, changes in bone and soft tissue dimensions including soft tissue profile&#xD;
        between pre-op and 4 months.&#xD;
  &#xD;
        Patients will be included in an intra-subject RCT on ARP following screening and written&#xD;
        consent at the Department of Periodontology and Oral Implantology of the University Hospital&#xD;
        in Ghent.&#xD;
  &#xD;
        A sample size calculation was performed in SPSS Statistics 28 (IBM, New York, USA) using the&#xD;
        paired samples t-test. The calculation was based on finding a mean difference of 0.5 mm in&#xD;
        the final soft tissue thickness between test and control sites with a standard deviation of&#xD;
        0.6 mm (Eeckhout et al., 2022). With alpha set at 0.05 and a power of 0.08, the sample size&#xD;
        calculation indicated 14 patients to be included. To compensate for possible dropouts, this&#xD;
        number was increased to 18 patients.&#xD;
  &#xD;
        Randomization, allocation concealment and blinding Since this is an intra-subject RCT, every&#xD;
        patient receives the test treatment as well as the control treatment. A coin flip will&#xD;
        determine which site in each patient is treated with the collagen matrix (test site) and&#xD;
        which one with the collagen membrane (control site). Group allocation will be determined just&#xD;
        after ARP and remains concealed for the evaluating examiner and statistician to allow for&#xD;
        unbiased registrations and analyses, respectively.&#xD;
  &#xD;
        Treatment procedures and postoperative care Patients will be instructed to take systemic&#xD;
        antibiotics (amoxicilline 2g) and anti-inflammatory medication (ibuprofen 600 mg) 1 h&#xD;
        pre-operatively. Just prior to the treatment, patients rinse with a 0.12% chlorhexidine&#xD;
        solution (Perio-aid® Intensive Care, Dent-Aid Benelux, Houten, The Netherlands) and local&#xD;
        anesthesia (Septanest special®, noradrenaline 1/100000; Septodont, Saint Maur des Fossés,&#xD;
        France) will be administered.&#xD;
  &#xD;
        Teeth are preferably extracted without flap elevation. When deemed necessary by the&#xD;
        clinician, papillary incisions can be made for minimal reflection, which enables to place&#xD;
        elevators without damaging soft tissues. Buccal soft tissues must never be raised. Following&#xD;
        wound debridement and rinsing, the amount of missing bone is measured with a periodontal&#xD;
        probe to the nearest 0.5 mm. Missing buccal bone is defined as the vertical distance between&#xD;
        the buccal bone crest and the midfacial soft tissue margin minus 3 mm. Then, both alveolar&#xD;
        sockets are filled with collagen-enriched deproteinized bovine bone mineral (C-DBBM, Bio-Oss&#xD;
        Collagen® 100 mg or 250 mg, Geistlich Pharma AG, Wolhusen, Switzerland) up to the level of&#xD;
        the lingual bone crest. The same procedure is performed for intact and non-intact alveoli.&#xD;
        Thereupon, a coin will be flipped to determine the assignment for either one of two treatment&#xD;
        modalities to each site:&#xD;
  &#xD;
          -  Test site: collagen matrix (Mucograft Seal®, Geistlich Pharma AG, Wolhusen, Switzerland)&#xD;
  &#xD;
          -  Control site: collagen membrane (BioGide Compressed® 13x25 mm, Geistlich Pharma AG,&#xD;
             Wolhusen, Switzerland) At the control site a small pouch is made at the buccal and&#xD;
             lingual aspect in order to place the membrane. The socket seal material is sutured with&#xD;
             at least 4 single sutures (Seralon 6/0, Serag Weissner, Naila, Germany) to protect the&#xD;
             underlying C-DBBM. Care is taken to ensure perfect approximation between the wound&#xD;
             margins and the socket seal material.&#xD;
  &#xD;
        Systemic antibiotics (amoxicilline 2g) will be continued for 4 days and anti-inflammatory&#xD;
        medication (ibuprofen 600 mg) is taken as deemed necessary by the patient. Patients rinse&#xD;
        with a 0.12% chlorhexidine solution twice daily for 1 week. Then, sutures are removed.&#xD;
  &#xD;
        Primary outcome: soft tissue thickness in the centre of the site Soft tissue thickness in the&#xD;
        centre of the site will be assessed using the method of Seyssens et al. (2019). A small-field&#xD;
        low-dose CBCT image is taken at T0 (immediately postop) and T3 (4 months). All CBCT images&#xD;
        will be obtained using a ProMax 3D Max device (Planmeca, Helsinki, Finland) with the same&#xD;
        standardized settings (90 kV, 6.3 mA, 9 seconds, voxel size 200 μm) with a same field of view&#xD;
        50 × 80 mm for each patient. Lip retractors are used to clearly visualize the external soft&#xD;
        tissue profile and patients will be instructed to fold the tongue backwards for the same&#xD;
        reason. Using specialized software (Invivo6, Osteoid Inc., Santa Clara, California, United&#xD;
        States), both CBCT images are superimposed. First, a reference line is drawn on the&#xD;
        postoperative CBCT (T0) at the level of the long axis of the extracted tooth. Then, the&#xD;
        software switch to the superimposed CBCT (T3) while keeping this reference line. Soft tissue&#xD;
        thickness in the centre of the site will be measured on the reference line as the vertical&#xD;
        distance between the alveolar proces and the soft tissue outline.&#xD;
  &#xD;
        Bucco-lingual and mesio-distal wound dimensions These are registered with a periodontal probe&#xD;
        to the nearest 0.5 mm at T0 (immediately postop), T1 (1 week) and T2 (3 weeks).&#xD;
  &#xD;
        Socket Wound Healing Score (SWHS) SWHS (Afat et al., 2019) is assessed at T1 (1 week), T2 (3&#xD;
        weeks) and T3 (4 months). SWHS is used to evaluate wound dehiscence, epithelialization,&#xD;
        quality of granulation tissue filling the post-extraction socket, and depth between early&#xD;
        granulation tissue and wound margin. SWHS is assessed on the basis of occlusal clinical&#xD;
        pictures and results in the following scores: 0 = Wound covered with keratinized gingiva,&#xD;
        pink tissue color, no bleeding, continuous with healthy tissue; 1 = Socket filled with&#xD;
        organized granulation tissue, no bleeding, collapsed to a depth of 0 - 2 mm from the buccal&#xD;
        gingival margin; 2 = Socket filled with organized granulation tissue, ¼ to ½ of the wound&#xD;
        showing red tissue color, no bleeding, collapsed to a depth of 2 - 4 mm from the buccal&#xD;
        gingival margin; 3 = Socket filled with unorganized granulation tissue, more than ½ of the&#xD;
        wound showing red tissue color, bleeding, no evidence of acute infection; 4 = Socket is&#xD;
        filled with foreign material (food, etc.) and shows signs of alveolitis.&#xD;
  &#xD;
        Changes in bone and soft tissue dimensions These will also be assessed on the same CBCT&#xD;
        images taken at T0 (immediately postop) and T3 (4 months). Using specialized software&#xD;
        (Invivo6, Osteoid Inc., Santa Clara, California, United States), both CBCT images are&#xD;
        superimposed. The following reference lines will be constructed on the postoperative CBCT&#xD;
        (T0) in the centre of the extracted tooth: the long axis of the extracted tooth, the level of&#xD;
        the lingual bone crest perpendicular to the long axis of the extracted tooth, level -1 mm,&#xD;
        level -3 mm and level -5 mm apical to the lingual bone crest and perpendicular to the long&#xD;
        axis of the extracted tooth. Bone width is registered at the three levels -1, -3, and -5 mm.&#xD;
        Buccal and lingual soft tissue height is measured as the vertical distance between the&#xD;
        alveolar process and the soft tissue outline parallel to the vertical reference line at the&#xD;
        most buccal and lingual part of the alveolar process. After completing all measurements on&#xD;
        the postoperative CBCT, the software changes to the superimposed CBCT (T3) image so that the&#xD;
        same measurements can be done while all keeping all reference lines. Finally, changes will be&#xD;
        calculated by subtracting the measurements at T3 from the measurements at T0.&#xD;
  &#xD;
        Changes in buccal soft tissue profile An intra-oral scan (Trios, 3shape, Copenhagen, Denmark)&#xD;
        will be taken at T0 (immediately postop) and T3 (4 months). The obtained digital surface&#xD;
        models in STL (Surface Tessellation Language) format will be imported into designated&#xD;
        software (SMOP, Swissmeda AG, Zurich, Switzerland) to analyze profilometric changes. A&#xD;
        study-relevant area of interest (AOI) at the buccal aspect is selected for each site. The AOI&#xD;
        reaches from 0.5 mm below the soft tissue margin to 4 mm more apical. In mesiodistal&#xD;
        dimension the AOI reaches from the mesial to the distal line angle. The AOI varies between&#xD;
        sites due to individual anatomic differences but will be kept constant in each site across&#xD;
        timepoints. Digital surface models are superimposed using the best-fit algorithm at the&#xD;
        unchanged adjacent tooth surfaces. A mean volumetric change (mm3) within the AOI for each&#xD;
        site from T0 to T3 is calculated by the software and divided by the AOI resulting in a mean&#xD;
        change in buccal soft tissue profile. Details on the method can be found in an earlier paper&#xD;
        (Eeckhout et al., 2020).&#xD;
  &#xD;
        Statistical analysis SPSS Statistics 28 (IBM, New York, USA) will be used for data analysis.&#xD;
        Mean values, standard deviations and 95% confidence intervals (CIs) will be calculated per&#xD;
        treatment group. The paired samples t-test is used to compare test and control sites at 4&#xD;
        months in terms of soft tissue thickness in the centre of the site and buccal soft tissue&#xD;
        profile.&#xD;
  &#xD;
        A linear mixed model will be used to analyze the other secondary outcomes (horizontal buccal&#xD;
        bone loss at the different levels, buccal and lingual soft tissue height, wound dimensions&#xD;
        and SWHS). Treatment group, time, and their interaction will be modeled as fixed factors.&#xD;
        Patient and tooth position as random factors. Estimated marginal means and 95% CIs will be&#xD;
        calculated per treatment group and per timepoint. The level of significance is set at 0.05.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">January 2, 2024</start_date>
    <completion_date type="Anticipated">January 2, 2025</completion_date>
    <primary_completion_date type="Anticipated">January 2, 2025</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>Crossover Assignment</intervention_model>
      <intervention_model_description>Split-mouth design, intra-subject RCT Patients receive both treatments: collagen matrix and collagen membranes</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Double (Investigator, Outcomes Assessor)</masking>
      <masking_description>It concerns a surgical intervention. Hence, the treating surgeon and patient cannot be masked. The investigators and outcome assessors are masked.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Soft tissue thickness in the centre of the site</measure>
      <time_frame>pre-op, 4 months</time_frame>
      <description>Changes in the soft tissue thickness at the centre of the site measured on CBCT</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Socket Wound Healing Score (SWHS)</measure>
      <time_frame>1 week, 3 weeks, 4 months</time_frame>
      <description>SWHS is used to evaluate wound dehiscence, epithelialization, quality of granulation tissue filling the post-extraction socket, and depth between early granulation tissue and wound margin</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes in bone and soft tissue dimensions</measure>
      <time_frame>4 months</time_frame>
      <description>Changes in bone and soft tissue dimensions measured on CBCT images</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes in buccal soft tissue profile</measure>
      <time_frame>pre-op, 4 months</time_frame>
      <description>Changes in buccal soft tissue profile measured by superimposing STL files using intra-oral scanners</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">18</enrollment>
    <condition>Soft Tissue Thickness</condition>
    <arm_group>
      <arm_group_label>Collagen membrane</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>BioGide Compressed® 13x25 mm, Geistlich Pharma AG, Wolhusen, Switzerland</description>
    </arm_group>
    <arm_group>
      <arm_group_label>collagen matrix</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Mucograft Seal®, Geistlich Pharma AG, Wolhusen, Switzerland</description>
    </arm_group>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Socket seal after alveolar ridge preservation</intervention_name>
      <description>Socket seal is performed after ARP. Using a collagen matrix or membrane the socket is sealed, at the control (membrane) site a small pouch is made at the buccal and lingual aspect. Monofilament sutures are used to secure the respective material in place.</description>
      <arm_group_label>Collagen membrane</arm_group_label>
      <arm_group_label>collagen matrix</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  At least 21 years old&#xD;
  &#xD;
            -  Good oral hygiene defined as a full-mouth plaque score ≤ 25% (O'Leary, Drake, &amp;&#xD;
               Naylor, 1972)&#xD;
  &#xD;
            -  Need for ARP after tooth extraction at two sites in the maxilla or mandible with &gt; 50%&#xD;
               buccal bone present following tooth extraction&#xD;
  &#xD;
            -  Signed informed consent&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Any systemic disease&#xD;
  &#xD;
            -  Pregnancy&#xD;
  &#xD;
            -  Smoking (will be specifically asked)&#xD;
  &#xD;
            -  Untreated periodontitis&#xD;
  &#xD;
            -  Untreated caries lesions&#xD;
  &#xD;
            -  Suppuration and/or active infection around the failing tooth&#xD;
  &#xD;
            -  Midfacial recession at the failing tooth&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>21 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Jan Georges Cosyn, PhD</last_name>
      <phone>+3293324017</phone>
      <email>jan.cosyn@ugent.be</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Maarten Glibert, PhD</last_name>
      <email>maarten.glibert@ugent.be</email>
    </overall_contact_backup>
    <reference>
      <citation>Afat IM, Akdogan ET, Gonul O. Effects of leukocyte- and platelet-rich fibrin alone and combined with hyaluronic acid on early soft tissue healing after surgical extraction of impacted mandibular third molars: A prospective clinical study. J Craniomaxillofac Surg. 2019 Feb;47(2):280-286. doi: 10.1016/j.jcms.2018.11.023. Epub 2018 Dec 3.</citation>
      <PMID>30579747</PMID>
    </reference>
    <reference>
      <citation>Avila-Ortiz G, Chambrone L, Vignoletti F. Effect of alveolar ridge preservation interventions following tooth extraction: A systematic review and meta-analysis. J Clin Periodontol. 2019 Jun;46 Suppl 21:195-223. doi: 10.1111/jcpe.13057. Erratum In: J Clin Periodontol. 2020 Jan;47(1):129.</citation>
      <PMID>30623987</PMID>
    </reference>
    <reference>
      <citation>Eeckhout C, Bouckaert E, Verleyen D, De Bruyckere T, Cosyn J. A 3-Year Prospective Study on a Porcine-Derived Acellular Collagen Matrix to Re-Establish Convexity at the Buccal Aspect of Single Implants in the Molar Area: A Volumetric Analysis. J Clin Med. 2020 May 22;9(5):1568. doi: 10.3390/jcm9051568.</citation>
      <PMID>32455863</PMID>
    </reference>
    <reference>
      <citation>Martins JR, Wagner TP, Vallim AC, Konflanz W, Schwendicke F, Celeste RK, Haas AN. Comparison of the efficacy of different techniques to seal the alveolus during alveolar ridge preservation: Meta-regression and network meta-analysis. J Clin Periodontol. 2022 Jul;49(7):694-705. doi: 10.1111/jcpe.13628. Epub 2022 Apr 29.</citation>
      <PMID>35451071</PMID>
    </reference>
    <reference>
      <citation>O'Leary TJ, Drake RB, Naylor JE. The plaque control record. J Periodontol. 1972 Jan;43(1):38. doi: 10.1902/jop.1972.43.1.38. No abstract available.</citation>
      <PMID>4500182</PMID>
    </reference>
    <reference>
      <citation>Seyssens L, Eghbali A, Christiaens V, De Bruyckere T, Doornewaard R, Cosyn J. A one-year prospective study on alveolar ridge preservation using collagen-enriched deproteinized bovine bone mineral and saddle connective tissue graft: A cone beam computed tomography analysis. Clin Implant Dent Relat Res. 2019 Oct;21(5):853-861. doi: 10.1111/cid.12843. Epub 2019 Aug 28.</citation>
      <PMID>31456345</PMID>
    </reference>
    <reference>
      <citation>Tonetti MS, Cortellini P, Graziani F, Cairo F, Lang NP, Abundo R, Conforti GP, Marquardt S, Rasperini G, Silvestri M, Wallkamm B, Wetzel A. Immediate versus delayed implant placement after anterior single tooth extraction: the timing randomized controlled clinical trial. J Clin Periodontol. 2017 Feb;44(2):215-224. doi: 10.1111/jcpe.12666. Epub 2017 Jan 31.</citation>
      <PMID>27978602</PMID>
    </reference>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 31, 2023</study_first_submitted>
    <study_first_submitted_qc>August 31, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 8, 2023</study_first_posted>
    <last_update_submitted>August 31, 2023</last_update_submitted>
    <last_update_submitted_qc>August 31, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 8, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>collagen matrix</keyword>
    <keyword>collagen membrane</keyword>
    <keyword>alveolar ridge preservation (ARP)</keyword>
    <keyword>CBCT analysis</keyword>
    <keyword>Volumetric analysis</keyword>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
      <ipd_description>If the data can be included in a meta-analysis upon request by the authors, they can be transferred</ipd_description>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06029322
  org study id: 1-15082023
  nct id: NCT06029322
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  Patients in need of extraction of two teeth in combination with alveolar ridge preservation
        will be invited to participate in intra-subject RCT on ARP. Prior to surgery, a small-field
        low-dose CBCT is taken.
  
        18 patients will be included, each contributing 1 surgical site to each treatment arm.
  
        Since this study is a intra-subject RCT randomization of the surgical site will be performed
        just after ARP by a coin flip. Randomization is concealed for the evaluating examiner and
        statistician.
  
        After ARP the collagen matrix or collagen membrane is used to seal the coronal aspect of the
        extraction socket.
  
        Soft tissue thickness in centre of the site will be determined using CBCT. Secondary outcomes
        include: Wound dimensions, socket wound healing score, changes in bone and soft tissue
        dimensions and changes in buccal soft tissue profile
  The primary study objective is to compare soft tissue thickness in the centre of the site
        between collagen matrix and collagen membrane at 4 months following ARP.
  
        Secondary study outcomes relate to the same comparison and include the following variables:
        wound reduction after 7 days and 21 days, socket wound healing score after 7 days, 21 days
        and 4 months, changes in bone and soft tissue dimensions including soft tissue profile
        between pre-op and 4 months.
  
        Patients will be included in an intra-subject RCT on ARP following screening and written
        consent at the Department of Periodontology and Oral Implantology of the University Hospital
        in Ghent.
  
        A sample size calculation was performed in SPSS Statistics 28 (IBM, New York, USA) using the
        paired samples t-test. The calculation was based on finding a mean difference of 0.5 mm in
        the final soft tissue thickness between test and control sites with a standard deviation of
        0.6 mm (Eeckhout et al., 2022). With alpha set at 0.05 and a power of 0.08, the sample size
        calculation indicated 14 patients to be included. To compensate for possible dropouts, this
        number was increased to 18 patients.
  
        Randomization, allocation concealment and blinding Since this is an intra-subject RCT, every
        patient receives the test treatment as well as the control treatment. A coin flip will
        determine which site in each patient is treated with the collagen matrix (test site) and
        which one with the collagen membrane (control site). Group allocation will be determined just
        after ARP and remains concealed for the evaluating examiner and statistician to allow for
        unbiased registrations and analyses, respectively.
  
        Treatment procedures and postoperative care Patients will be instructed to take systemic
        antibiotics (amoxicilline 2g) and anti-inflammatory medication (ibuprofen 600 mg) 1 h
        pre-operatively. Just prior to the treatment, patients rinse with a 0.12% chlorhexidine
        solution (Perio-aid® Intensive Care, Dent-Aid Benelux, Houten, The Netherlands) and local
        anesthesia (Septanest special®, noradrenaline 1/100000; Septodont, Saint Maur des Fossés,
        France) will be administered.
  
        Teeth are preferably extracted without flap elevation. When deemed necessary by the
        clinician, papillary incisions can be made for minimal reflection, which enables to place
        elevators without damaging soft tissues. Buccal soft tissues must never be raised. Following
        wound debridement and rinsing, the amount of missing bone is measured with a periodontal
        probe to the nearest 0.5 mm. Missing buccal bone is defined as the vertical distance between
        the buccal bone crest and the midfacial soft tissue margin minus 3 mm. Then, both alveolar
        sockets are filled with collagen-enriched deproteinized bovine bone mineral (C-DBBM, Bio-Oss
        Collagen® 100 mg or 250 mg, Geistlich Pharma AG, Wolhusen, Switzerland) up to the level of
        the lingual bone crest. The same procedure is performed for intact and non-intact alveoli.
        Thereupon, a coin will be flipped to determine the assignment for either one of two treatment
        modalities to each site:
  
          -  Test site: collagen matrix (Mucograft Seal®, Geistlich Pharma AG, Wolhusen, Switzerland)
  
          -  Control site: collagen membrane (BioGide Compressed® 13x25 mm, Geistlich Pharma AG,
             Wolhusen, Switzerland) At the control site a small pouch is made at the buccal and
             lingual aspect in order to place the membrane. The socket seal material is sutured with
             at least 4 single sutures (Seralon 6/0, Serag Weissner, Naila, Germany) to protect the
             underlying C-DBBM. Care is taken to ensure perfect approximation between the wound
             margins and the socket seal material.
  
        Systemic antibiotics (amoxicilline 2g) will be continued for 4 days and anti-inflammatory
        medication (ibuprofen 600 mg) is taken as deemed necessary by the patient. Patients rinse
        with a 0.12% chlorhexidine solution twice daily for 1 week. Then, sutures are removed.
  
        Primary outcome: soft tissue thickness in the centre of the site Soft tissue thickness in the
        centre of the site will be assessed using the method of Seyssens et al. (2019). A small-field
        low-dose CBCT image is taken at T0 (immediately postop) and T3 (4 months). All CBCT images
        will be obtained using a ProMax 3D Max device (Planmeca, Helsinki, Finland) with the same
        standardized settings (90 kV, 6.3 mA, 9 seconds, voxel size 200 μm) with a same field of view
        50 × 80 mm for each patient. Lip retractors are used to clearly visualize the external soft
        tissue profile and patients will be instructed to fold the tongue backwards for the same
        reason. Using specialized software (Invivo6, Osteoid Inc., Santa Clara, California, United
        States), both CBCT images are superimposed. First, a reference line is drawn on the
        postoperative CBCT (T0) at the level of the long axis of the extracted tooth. Then, the
        software switch to the superimposed CBCT (T3) while keeping this reference line. Soft tissue
        thickness in the centre of the site will be measured on the reference line as the vertical
        distance between the alveolar proces and the soft tissue outline.
  
        Bucco-lingual and mesio-distal wound dimensions These are registered with a periodontal probe
        to the nearest 0.5 mm at T0 (immediately postop), T1 (1 week) and T2 (3 weeks).
  
        Socket Wound Healing Score (SWHS) SWHS (Afat et al., 2019) is assessed at T1 (1 week), T2 (3
        weeks) and T3 (4 months). SWHS is used to evaluate wound dehiscence, epithelialization,
        quality of granulation tissue filling the post-extraction socket, and depth between early
        granulation tissue and wound margin. SWHS is assessed on the basis of occlusal clinical
        pictures and results in the following scores: 0 = Wound covered with keratinized gingiva,
        pink tissue color, no bleeding, continuous with healthy tissue; 1 = Socket filled with
        organized granulation tissue, no bleeding, collapsed to a depth of 0 - 2 mm from the buccal
        gingival margin; 2 = Socket filled with organized granulation tissue, ¼ to ½ of the wound
        showing red tissue color, no bleeding, collapsed to a depth of 2 - 4 mm from the buccal
        gingival margin; 3 = Socket filled with unorganized granulation tissue, more than ½ of the
        wound showing red tissue color, bleeding, no evidence of acute infection; 4 = Socket is
        filled with foreign material (food, etc.) and shows signs of alveolitis.
  
        Changes in bone and soft tissue dimensions These will also be assessed on the same CBCT
        images taken at T0 (immediately postop) and T3 (4 months). Using specialized software
        (Invivo6, Osteoid Inc., Santa Clara, California, United States), both CBCT images are
        superimposed. The following reference lines will be constructed on the postoperative CBCT
        (T0) in the centre of the extracted tooth: the long axis of the extracted tooth, the level of
        the lingual bone crest perpendicular to the long axis of the extracted tooth, level -1 mm,
        level -3 mm and level -5 mm apical to the lingual bone crest and perpendicular to the long
        axis of the extracted tooth. Bone width is registered at the three levels -1, -3, and -5 mm.
        Buccal and lingual soft tissue height is measured as the vertical distance between the
        alveolar process and the soft tissue outline parallel to the vertical reference line at the
        most buccal and lingual part of the alveolar process. After completing all measurements on
        the postoperative CBCT, the software changes to the superimposed CBCT (T3) image so that the
        same measurements can be done while all keeping all reference lines. Finally, changes will be
        calculated by subtracting the measurements at T3 from the measurements at T0.
  
        Changes in buccal soft tissue profile An intra-oral scan (Trios, 3shape, Copenhagen, Denmark)
        will be taken at T0 (immediately postop) and T3 (4 months). The obtained digital surface
        models in STL (Surface Tessellation Language) format will be imported into designated
        software (SMOP, Swissmeda AG, Zurich, Switzerland) to analyze profilometric changes. A
        study-relevant area of interest (AOI) at the buccal aspect is selected for each site. The AOI
        reaches from 0.5 mm below the soft tissue margin to 4 mm more apical. In mesiodistal
        dimension the AOI reaches from the mesial to the distal line angle. The AOI varies between
        sites due to individual anatomic differences but will be kept constant in each site across
        timepoints. Digital surface models are superimposed using the best-fit algorithm at the
        unchanged adjacent tooth surfaces. A mean volumetric change (mm3) within the AOI for each
        site from T0 to T3 is calculated by the software and divided by the AOI resulting in a mean
        change in buccal soft tissue profile. Details on the method can be found in an earlier paper
        (Eeckhout et al., 2020).
  
        Statistical analysis SPSS Statistics 28 (IBM, New York, USA) will be used for data analysis.
        Mean values, standard deviations and 95% confidence intervals (CIs) will be calculated per
        treatment group. The paired samples t-test is used to compare test and control sites at 4
        months in terms of soft tissue thickness in the centre of the site and buccal soft tissue
        profile.
  
        A linear mixed model will be used to analyze the other secondary outcomes (horizontal buccal
        bone loss at the different levels, buccal and lingual soft tissue height, wound dimensions
        and SWHS). Treatment group, time, and their interaction will be modeled as fixed factors.
        Patient and tooth position as random factors. Estimated marginal means and 95% CIs will be
        calculated per treatment group and per timepoint. The level of significance is set at 0.05.
  allocation: Randomized
  intervention model: Crossover Assignment
  intervention model description: Split-mouth design, intra-subject RCT Patients receive both treatments: collagen matrix and collagen membranes
  primary purpose: Treatment
  masking: Double (Investigator, Outcomes Assessor)
  masking description: It concerns a surgical intervention. Hence, the treating surgeon and patient cannot be masked. The investigators and outcome assessors are masked.
  measure: Soft tissue thickness in the centre of the site
  time frame: pre-op, 4 months
  description: Changes in the soft tissue thickness at the centre of the site measured on CBCT
  measure: Socket Wound Healing Score (SWHS)
  time frame: 1 week, 3 weeks, 4 months
  description: SWHS is used to evaluate wound dehiscence, epithelialization, quality of granulation tissue filling the post-extraction socket, and depth between early granulation tissue and wound margin
  measure: Changes in bone and soft tissue dimensions
  time frame: 4 months
  description: Changes in bone and soft tissue dimensions measured on CBCT images
  measure: Changes in buccal soft tissue profile
  time frame: pre-op, 4 months
  description: Changes in buccal soft tissue profile measured by superimposing STL files using intra-oral scanners
  arm group label: Collagen membrane
  arm group type: Active Comparator
  description: BioGide Compressed® 13x25 mm, Geistlich Pharma AG, Wolhusen, Switzerland
  arm group label: collagen matrix
  arm group type: Experimental
  description: Mucograft Seal®, Geistlich Pharma AG, Wolhusen, Switzerland
  intervention type: Procedure
  intervention name: Socket seal after alveolar ridge preservation
  description: Socket seal is performed after ARP. Using a collagen matrix or membrane the socket is sealed, at the control (membrane) site a small pouch is made at the buccal and lingual aspect. Monofilament sutures are used to secure the respective material in place.
  arm group label: Collagen membrane
  arm group label: collagen matrix
  criteria: 
  gender: All
  minimum age: 21 Years
  maximum age: N/A
  healthy volunteers: Accepts Healthy Volunteers
  last name: Jan Georges Cosyn, PhD
  phone: +3293324017
  email: jan.cosyn@ugent.be
  last name: Maarten Glibert, PhD
  email: maarten.glibert@ugent.be
  citation: Afat IM, Akdogan ET, Gonul O. Effects of leukocyte- and platelet-rich fibrin alone and combined with hyaluronic acid on early soft tissue healing after surgical extraction of impacted mandibular third molars: A prospective clinical study. J Craniomaxillofac Surg. 2019 Feb;47(2):280-286. doi: 10.1016/j.jcms.2018.11.023. Epub 2018 Dec 3.
  PMID: 30579747
  citation: Avila-Ortiz G, Chambrone L, Vignoletti F. Effect of alveolar ridge preservation interventions following tooth extraction: A systematic review and meta-analysis. J Clin Periodontol. 2019 Jun;46 Suppl 21:195-223. doi: 10.1111/jcpe.13057. Erratum In: J Clin Periodontol. 2020 Jan;47(1):129.
  PMID: 30623987
  citation: Eeckhout C, Bouckaert E, Verleyen D, De Bruyckere T, Cosyn J. A 3-Year Prospective Study on a Porcine-Derived Acellular Collagen Matrix to Re-Establish Convexity at the Buccal Aspect of Single Implants in the Molar Area: A Volumetric Analysis. J Clin Med. 2020 May 22;9(5):1568. doi: 10.3390/jcm9051568.
  PMID: 32455863
  citation: Martins JR, Wagner TP, Vallim AC, Konflanz W, Schwendicke F, Celeste RK, Haas AN. Comparison of the efficacy of different techniques to seal the alveolus during alveolar ridge preservation: Meta-regression and network meta-analysis. J Clin Periodontol. 2022 Jul;49(7):694-705. doi: 10.1111/jcpe.13628. Epub 2022 Apr 29.
  PMID: 35451071
  citation: O'Leary TJ, Drake RB, Naylor JE. The plaque control record. J Periodontol. 1972 Jan;43(1):38. doi: 10.1902/jop.1972.43.1.38. No abstract available.
  PMID: 4500182
  citation: Seyssens L, Eghbali A, Christiaens V, De Bruyckere T, Doornewaard R, Cosyn J. A one-year prospective study on alveolar ridge preservation using collagen-enriched deproteinized bovine bone mineral and saddle connective tissue graft: A cone beam computed tomography analysis. Clin Implant Dent Relat Res. 2019 Oct;21(5):853-861. doi: 10.1111/cid.12843. Epub 2019 Aug 28.
  PMID: 31456345
  citation: Tonetti MS, Cortellini P, Graziani F, Cairo F, Lang NP, Abundo R, Conforti GP, Marquardt S, Rasperini G, Silvestri M, Wallkamm B, Wetzel A. Immediate versus delayed implant placement after anterior single tooth extraction: the timing randomized controlled clinical trial. J Clin Periodontol. 2017 Feb;44(2):215-224. doi: 10.1111/jcpe.12666. Epub 2017 Jan 31.
  PMID: 27978602
  responsible party type: Sponsor
  sharing ipd: Undecided
  ipd description: If the data can be included in a meta-analysis upon request by the authors, they can be transferred