<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/NCT02981017</url>
  </required_header>
  <id_info>
    <org_study_id>16-001257</org_study_id>
    <nct_id>NCT02981017</nct_id>
  </id_info>
  <brief_title>Improvement of Outcomes in Draf III/Endoscopic Modified Lothrop Procedure</brief_title>
  <official_title>Prospective Study for Improvement in Outcomes Following Draf III/Endoscopic Modified Lothrop Procedure Using a Porcine Intestinal Submucosal Graft</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, Los Angeles</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of California, Los Angeles</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      We propose a randomized, single-blinded, prospective trial in order to evaluate the efficacy&#xD;
      of the Cook Biodesign ENT Repair graft in improving outcomes after the Draf III or Endoscopic&#xD;
      Modified Lothrop procedure. The Cook Biodesign ENT Repair graft is a porcine intestinal&#xD;
      submucosal xenograft which has been FDA approved for use as an adjunct to natural healing&#xD;
      process in the sinonasal cavity. The Draf III or Endoscopic Modified Lothrop involved&#xD;
      creating a large unified drainage pathway for refractory frontal sinusitis. After the&#xD;
      procedure is completed, there is exposed bone along the frontal beak region which can become&#xD;
      a nidus for inflammation, crusting and eventual scarring, leading to stenosis or even&#xD;
      complete blockage of the frontal sinuses. The Cook Biodesign will be used to cover this&#xD;
      exposed bone in order to potentially reduce the inflammation, crusting and scarring and&#xD;
      possibly improve outcomes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Chronic rhinosinusitis (CRS) is an inflammatory disorder affecting the sinonasal mucosa.&#xD;
      Chronic symptoms include facial pain and pressure, nasal airway obstruction, anosmia and&#xD;
      nasal discharge (sometimes purulent), in addition to significant effects on overall quality&#xD;
      of life. The cost of CRS is estimated to be approximately $4 billion per year and results in&#xD;
      over 20 million physician visits per year. The frontal sinuses are paired paranasal sinuses&#xD;
      housed superiorly and anteriorly in the frontal bone on each side, separated by an&#xD;
      inter-sinus septum which is contiguous with the nasal septum. The frontal sinuses, like the&#xD;
      other paranasal sinuses, can be affected in chronic rhinosinusitis, with inflammation of the&#xD;
      frontal sinus outflow tract causing obstruction and subsequent symptoms. First line therapy&#xD;
      involves medical therapy often with combination of antibiotics, nasal saline irrigation,&#xD;
      topical and/or systemic corticosteroids, with endoscopic sinus surgical therapy reserved for&#xD;
      patients with persistent symptoms after medical therapy.&#xD;
&#xD;
      Surgical therapy of the frontal sinus is the most technically demanding aspect of endoscopic&#xD;
      sinus surgery, and due to this, surgical dissection of the frontal sinuses has been&#xD;
      discouraged in the past. Otolaryngology textbooks also emphasize that chronic frontal sinus&#xD;
      disease may be related to unnecessary instrumentation of the frontal recess. With recent&#xD;
      advances in endoscopic sinus surgery and the advent of balloon sinusotomy, the rate of&#xD;
      frontal sinus surgery has more than doubled from 2000 to 2009.&#xD;
&#xD;
      Primary frontal sinus surgery can be approached with balloon dilation or by endoscopic&#xD;
      sinusotomy. Endoscopic sinusotomy of the frontal sinus involves increasing the size of the&#xD;
      frontal recess with anterior ethmoidectomy and removal of the agger nasi cell anteriorly, and&#xD;
      any frontal cells that may be present. Frontal sinus surgery is effective, as evidenced by a&#xD;
      recent study analyzing long-term results after primary frontal sinus surgery showing a&#xD;
      patency rate of 92% in a nearly 2-year average follow up period.&#xD;
&#xD;
      Refractory frontal sinusitis can be addressed surgically through external or 'extended'&#xD;
      endonasal approaches. Historically, external approaches were first utilized, with&#xD;
      introduction of osteoplastic flap techniques by Brieger in the 1890s. Lothrop introduced the&#xD;
      Lothrop Procedure in 1914 which required an osteoplastic flap with removal of the frontal&#xD;
      sinus floor and intersinus septum along with the upper aspect of the nasal septum to create a&#xD;
      unified drainage pathway for the frontal sinuses. In the 1950s, Montgomery popularized the&#xD;
      frontal sinus obliteration through osteoplastic flap approach leaving the frontal sinuses&#xD;
      permanently non-functional through obliteration with fat or other materials. Though these&#xD;
      external approaches often had high success rates, they require extensive dissection and are&#xD;
      associated with a high morbidity and complication rate upwards of 20%. These complications&#xD;
      included dural exposure, dural laceration with cerebrospinal fluid leak, orbital injury,&#xD;
      forehead numbness, osteomyelitis and mucocele formation.&#xD;
&#xD;
      In 1991, Wolfgang Draf described an endoscopic approach to create a common drainage pathway&#xD;
      akin to the Lothrop procedure which is now called the Endoscopic Modified Lothrop (EMLP) or&#xD;
      Draf III procedure. Currently, the EMLP provides an endoscopic alternative for persistent&#xD;
      frontal sinus disease after initial frontal sinusotomy, prior to consideration of frontal&#xD;
      sinus obliteration through an osteoplastic flap approach. The EMLP involves drilling out the&#xD;
      frontal sinus ostia on both sides and combining them through a superior septectomy, creating&#xD;
      a large common drainage pathway for the two frontal sinuses. The EMLP offers reduced&#xD;
      morbidity, shorter hospital stay, improved cosmetics, reduced blood loss and preservation of&#xD;
      a functional frontal sinus. One meta-analysis study of 18 observational studies showed a&#xD;
      restenosis rate of 19% and an overall failure rate of 13.9% (with failure defined as&#xD;
      requiring revision surgery), with failure rates ranging from 0-33%. Restenosis of the frontal&#xD;
      sinus ostium after EMLP is often attributed to a combination of scarring, adhesions or&#xD;
      neo-osteogenesis, which occurs secondary to exposed bone after the surgical procedure. The&#xD;
      exposed osteitic bone is believed to act as a source for inflammation and osteoblastic&#xD;
      activity. Persistent mucosal disease has also been postulated as a contributor to&#xD;
      postoperative stenosis after EMLP. Prevention of restenosis has been attempted with use of&#xD;
      stents or medical therapy with topical application of mitomycin C and steroids with variable&#xD;
      results.&#xD;
&#xD;
      Recent studies have attempted to address this issue by using mucosal grafts to cover the&#xD;
      exposed frontal bone after EMLP. These studies describe using free or pedicled mucosal grafts&#xD;
      from various sites in the nasal cavity to cover the bare bone exposed after EMLP drill out&#xD;
      procedure. Two studies reported results using free mucosal grafts to cover the exposed bone&#xD;
      and showed encouraging results, with patency rates 95% and 100%. Another study using a&#xD;
      pedicled flap based off the anterior ethmoidal artery showed no restenosis in 4 patients.&#xD;
      These studies utilize mucosa mostly from the nasal septum at the region of the superior&#xD;
      septectomy which would otherwise be discarded, but they do also report use of inferior&#xD;
      turbinate mucosa harvesting. Though minimal morbidity related to mucosal harvest was&#xD;
      reported, any mucosal harvest from sites other than the operative site has the potential for&#xD;
      creating additional postoperative morbidity. In addition, use of mucosa from a diseased&#xD;
      mucosal cavity may not be optimal. Reducing rates of restenosis and failure in EMLP will&#xD;
      allow for improved outcomes following this procedure and may prevent progression to more&#xD;
      invasive and extensive surgical procedures.&#xD;
&#xD;
      This study will utilize a proprietary porcine intestinal submucosa graft Cook Biodesign™ ENT&#xD;
      Repair graft to cover the exposed bone on the nasofrontal beak region following EMLP in order&#xD;
      to evaluate its effects on mucosal healing and reduction of restenosis rates of the&#xD;
      surgically augmented frontal sinus ostium after the Endoscopic Modified Lothrop Procedure.&#xD;
      The Cook Biodesign™ ENT Repair for nasal mucosal replacement has been in use for sinonasal&#xD;
      surgery since its Food and Drug Administration (FDA) approval in 2013. The Cook Biodesign™&#xD;
      ENT Repair graft is FDA approved for prescription use to &quot;separate tissue or structures&#xD;
      compromised by surgical trauma, help control minimal bleeding, and act as an adjunct to aid&#xD;
      in the natural healing process. The device is indicated for use where an open wound dressing&#xD;
      material is required in the nasal and/or sinus cavities following nasal and/or sinus surgery&#xD;
      where separation of tissues or structures is desired.&quot;&#xD;
&#xD;
      The use of xenograft material in the method proposed in this submission has not been studied&#xD;
      extensively. However, using free mucosal grafts or pedicled mucosal flaps after EMLP as&#xD;
      previously discussed, have shown promise. The Cook Biodesign™ has been used preliminarily&#xD;
      with patients in this proposed setting with good anecdotal results, including reduced&#xD;
      crusting and good postoperative outcomes, however, its use has not yet been formally&#xD;
      evaluated. The Cook Biodesign™ graft has several advantages over using native mucosal grafts:&#xD;
      it is readily available and does not require harvest thus reducing operative times and&#xD;
      potential morbidity from mucosa harvest sites, it is thinner than sinus mucosa and handled&#xD;
      with ease, and it has tissue characteristics that promote wound healing. With the Cook&#xD;
      Biodesign™, our hypothesis is that its use after EMLP surgery will allow for reduction of&#xD;
      exposed bone in the sinonasal cavity and thus reduce inflammation, crusting and ultimately&#xD;
      reduce restenosis and failure rates. Additionally, we hypothesize that reduction of crusting&#xD;
      and inflammation will lead to improved patient reported symptom and quality of life scores on&#xD;
      the Sinonasal Outcomes Test-22 (SNOT-22) questionnaire.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Decided to do a different clinical trial opportunity.&#xD;
  </why_stopped>
  <start_date type="Actual">November 1, 2016</start_date>
  <completion_date type="Actual">December 28, 2019</completion_date>
  <primary_completion_date type="Actual">December 28, 2019</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>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Frontal sinus stenosis</measure>
    <time_frame>1 year</time_frame>
    <description>Evaluate the size of the frontal sinus outflow tract over one year after surgery</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of postoperative debridements</measure>
    <time_frame>1 year</time_frame>
    <description>Track the number of debridements required in the postoperative period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Need for further surgical intervention</measure>
    <time_frame>1 year</time_frame>
    <description>Track if any further surgical procedures (in office or in operating room) that are required during postoperative period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of postoperative infections</measure>
    <time_frame>1 year</time_frame>
    <description>Track the number of postoperative sinus infections, proven by culture, as well as the number of antibiotic courses required for treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lund Kennedy Endoscopy Score</measure>
    <time_frame>1 year</time_frame>
    <description>Evaluation of the sinuses using nasal endoscopy and objective measurement using the validated Lund-Kennedy Endoscopy score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>SNOT-22 score</measure>
    <time_frame>1 year</time_frame>
    <description>Evaluation of patient quality of life using a validated questionnaire called the Sinonasal Outcome Test (SNOT) - 22.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Chronic Sinusitis</condition>
  <condition>Frontal Sinusitis</condition>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Subjects within the control arm will undergo the Draf III/Endoscopic Modified Lothrop procedure to address their sinus disease. At the end of the procedure, no Cook Biodesign Porcine intestinal submucosal graft will be used to cover the operative site. Light nasal packing will be placed in the nasal cavity for hemostasis. No placebo will be utilized.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cook Biodesign</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects within the experimental group will undergo the Draf III/Endoscopic Modified Lothrop procedure to address their sinus disease. At the end of the procedure, a small piece of Cook Biodesign porcine intestinal submucosal xenograft will be used to cover the exposed bone of the operative site along the frontal beak. It will be bolstered with light nasal packing to keep the graft in place during healing.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Porcine Intestinal submucosal xenograft</intervention_name>
    <description>Cook Biodesign ENT repair graft will be used in the experimental group to cover exposed bone in the sinonasal cavity as a result of the Draf III/endoscopic modified lothrop procedure.</description>
    <arm_group_label>Cook Biodesign</arm_group_label>
    <other_name>Cook Biodesign ENT Repair</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Any patient older than 18 years of age&#xD;
&#xD;
          -  Frontal sinusitis refractory to previous surgical and/or medical therapy&#xD;
&#xD;
          -  Patient with skull base neoplasm which requires Draf III or Endoscopic Modified&#xD;
             Lothrop for exposure in excision of tumor&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous Draf III or Endoscopic Modified Lothrop Procedure&#xD;
&#xD;
          -  Allergy or objection to use of porcine-based graft material&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jeffrey D Suh, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California Los Angeles, Department of Head and Neck Surgery</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California Los Angeles</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Pleis JR, Lucas JW. Summary health statistics for U.S. adults: National Health Interview Survey, 2007. Vital Health Stat 10. 2009 May;(240):1-159.</citation>
    <PMID>19645319</PMID>
  </reference>
  <reference>
    <citation>Naidoo Y, Wen D, Bassiouni A, Keen M, Wormald PJ. Long-term results after primary frontal sinus surgery. Int Forum Allergy Rhinol. 2012 May-Jun;2(3):185-90. doi: 10.1002/alr.21015. Epub 2012 Jan 17.</citation>
    <PMID>22253224</PMID>
  </reference>
  <reference>
    <citation>Pynnonen MA, Davis MM. Extent of sinus surgery, 2000 to 2009: a population-based study. Laryngoscope. 2014 Apr;124(4):820-5. doi: 10.1002/lary.24335. Epub 2013 Oct 2.</citation>
    <PMID>23900802</PMID>
  </reference>
  <reference>
    <citation>Anderson P, Sindwani R. Safety and efficacy of the endoscopic modified Lothrop procedure: a systematic review and meta-analysis. Laryngoscope. 2009 Sep;119(9):1828-33. doi: 10.1002/lary.20565.</citation>
    <PMID>19554631</PMID>
  </reference>
  <reference>
    <citation>Wormald PJ. Salvage frontal sinus surgery: the endoscopic modified Lothrop procedure. Laryngoscope. 2003 Feb;113(2):276-83. doi: 10.1097/00005537-200302000-00015.</citation>
    <PMID>12567082</PMID>
  </reference>
  <reference>
    <citation>Tran KN, Beule AG, Singal D, Wormald PJ. Frontal ostium restenosis after the endoscopic modified Lothrop procedure. Laryngoscope. 2007 Aug;117(8):1457-62. doi: 10.1097/MLG.0b013e31806865be.</citation>
    <PMID>17585278</PMID>
  </reference>
  <reference>
    <citation>Ye T, Hwang PH, Huang Z, Huang Q, Xian J, Li C, Zhou B. Frontal ostium neo-osteogenesis and patency after Draf III procedure: a computer-assisted study. Int Forum Allergy Rhinol. 2014 Sep;4(9):739-44. doi: 10.1002/alr.21357. Epub 2014 Jul 30.</citation>
    <PMID>25079177</PMID>
  </reference>
  <reference>
    <citation>AlQahtani A, Bignami M, Terranova P, Digilio E, Basilico F, Abdulrahman S, Castelnuovo P. Newly designed double-vascularized nasoseptal flap to prevent restenosis after endoscopic modified Lothrop procedure (Draf III): laboratory investigation. Eur Arch Otorhinolaryngol. 2014 Nov;271(11):2951-5. doi: 10.1007/s00405-014-2961-2. Epub 2014 Mar 8.</citation>
    <PMID>24609647</PMID>
  </reference>
  <reference>
    <citation>Conger BT Jr, Riley K, Woodworth BA. The Draf III mucosal grafting technique: a prospective study. Otolaryngol Head Neck Surg. 2012 Apr;146(4):664-8. doi: 10.1177/0194599811432423. Epub 2012 Jan 6.</citation>
    <PMID>22228601</PMID>
  </reference>
  <reference>
    <citation>Hildenbrand T, Wormald PJ, Weber RK. Endoscopic frontal sinus drainage Draf type III with mucosal transplants. Am J Rhinol Allergy. 2012 Mar-Apr;26(2):148-51. doi: 10.2500/ajra.2012.26.3731.</citation>
    <PMID>22487293</PMID>
  </reference>
  <reference>
    <citation>Seyedhadi S, Mojtaba MA, Shahin B, Hoseinali K. The Draf III septal flap technique: a preliminary report. Am J Otolaryngol. 2013 Sep-Oct;34(5):399-402. doi: 10.1016/j.amjoto.2013.01.019. Epub 2013 Feb 26.</citation>
    <PMID>23452383</PMID>
  </reference>
  <reference>
    <citation>Wei CC, Sama A. What is the evidence for the use of mucosal flaps in Draf III procedures? Curr Opin Otolaryngol Head Neck Surg. 2014 Feb;22(1):63-7. doi: 10.1097/MOO.0000000000000023.</citation>
    <PMID>24335916</PMID>
  </reference>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>November 30, 2016</study_first_submitted>
  <study_first_submitted_qc>November 30, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 2, 2016</study_first_posted>
  <last_update_submitted>October 28, 2020</last_update_submitted>
  <last_update_submitted_qc>October 28, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 30, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of California, Los Angeles</investigator_affiliation>
    <investigator_full_name>Jeffrey D. Suh</investigator_full_name>
    <investigator_title>Assistant Professor, Department of Head and Neck Surgery</investigator_title>
  </responsible_party>
  <keyword>Chronic sinusitis</keyword>
  <keyword>Frontal sinusitis</keyword>
  <keyword>Skull base neoplasm</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sinusitis</mesh_term>
    <mesh_term>Frontal Sinusitis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT02981017
org study id: 16-001257
nct id: NCT02981017
lead sponsor: 
has dmc: No
We propose a randomized, single-blinded, prospective trial in order to evaluate the efficacy
      of the Cook Biodesign ENT Repair graft in improving outcomes after the Draf III or Endoscopic
      Modified Lothrop procedure. The Cook Biodesign ENT Repair graft is a porcine intestinal
      submucosal xenograft which has been FDA approved for use as an adjunct to natural healing
      process in the sinonasal cavity. The Draf III or Endoscopic Modified Lothrop involved
      creating a large unified drainage pathway for refractory frontal sinusitis. After the
      procedure is completed, there is exposed bone along the frontal beak region which can become
      a nidus for inflammation, crusting and eventual scarring, leading to stenosis or even
      complete blockage of the frontal sinuses. The Cook Biodesign will be used to cover this
      exposed bone in order to potentially reduce the inflammation, crusting and scarring and
      possibly improve outcomes.
Chronic rhinosinusitis (CRS) is an inflammatory disorder affecting the sinonasal mucosa.
      Chronic symptoms include facial pain and pressure, nasal airway obstruction, anosmia and
      nasal discharge (sometimes purulent), in addition to significant effects on overall quality
      of life. The cost of CRS is estimated to be approximately $4 billion per year and results in
      over 20 million physician visits per year. The frontal sinuses are paired paranasal sinuses
      housed superiorly and anteriorly in the frontal bone on each side, separated by an
      inter-sinus septum which is contiguous with the nasal septum. The frontal sinuses, like the
      other paranasal sinuses, can be affected in chronic rhinosinusitis, with inflammation of the
      frontal sinus outflow tract causing obstruction and subsequent symptoms. First line therapy
      involves medical therapy often with combination of antibiotics, nasal saline irrigation,
      topical and/or systemic corticosteroids, with endoscopic sinus surgical therapy reserved for
      patients with persistent symptoms after medical therapy.

      Surgical therapy of the frontal sinus is the most technically demanding aspect of endoscopic
      sinus surgery, and due to this, surgical dissection of the frontal sinuses has been
      discouraged in the past. Otolaryngology textbooks also emphasize that chronic frontal sinus
      disease may be related to unnecessary instrumentation of the frontal recess. With recent
      advances in endoscopic sinus surgery and the advent of balloon sinusotomy, the rate of
      frontal sinus surgery has more than doubled from 2000 to 2009.

      Primary frontal sinus surgery can be approached with balloon dilation or by endoscopic
      sinusotomy. Endoscopic sinusotomy of the frontal sinus involves increasing the size of the
      frontal recess with anterior ethmoidectomy and removal of the agger nasi cell anteriorly, and
      any frontal cells that may be present. Frontal sinus surgery is effective, as evidenced by a
      recent study analyzing long-term results after primary frontal sinus surgery showing a
      patency rate of 92% in a nearly 2-year average follow up period.

      Refractory frontal sinusitis can be addressed surgically through external or 'extended'
      endonasal approaches. Historically, external approaches were first utilized, with
      introduction of osteoplastic flap techniques by Brieger in the 1890s. Lothrop introduced the
      Lothrop Procedure in 1914 which required an osteoplastic flap with removal of the frontal
      sinus floor and intersinus septum along with the upper aspect of the nasal septum to create a
      unified drainage pathway for the frontal sinuses. In the 1950s, Montgomery popularized the
      frontal sinus obliteration through osteoplastic flap approach leaving the frontal sinuses
      permanently non-functional through obliteration with fat or other materials. Though these
      external approaches often had high success rates, they require extensive dissection and are
      associated with a high morbidity and complication rate upwards of 20%. These complications
      included dural exposure, dural laceration with cerebrospinal fluid leak, orbital injury,
      forehead numbness, osteomyelitis and mucocele formation.

      In 1991, Wolfgang Draf described an endoscopic approach to create a common drainage pathway
      akin to the Lothrop procedure which is now called the Endoscopic Modified Lothrop (EMLP) or
      Draf III procedure. Currently, the EMLP provides an endoscopic alternative for persistent
      frontal sinus disease after initial frontal sinusotomy, prior to consideration of frontal
      sinus obliteration through an osteoplastic flap approach. The EMLP involves drilling out the
      frontal sinus ostia on both sides and combining them through a superior septectomy, creating
      a large common drainage pathway for the two frontal sinuses. The EMLP offers reduced
      morbidity, shorter hospital stay, improved cosmetics, reduced blood loss and preservation of
      a functional frontal sinus. One meta-analysis study of 18 observational studies showed a
      restenosis rate of 19% and an overall failure rate of 13.9% (with failure defined as
      requiring revision surgery), with failure rates ranging from 0-33%. Restenosis of the frontal
      sinus ostium after EMLP is often attributed to a combination of scarring, adhesions or
      neo-osteogenesis, which occurs secondary to exposed bone after the surgical procedure. The
      exposed osteitic bone is believed to act as a source for inflammation and osteoblastic
      activity. Persistent mucosal disease has also been postulated as a contributor to
      postoperative stenosis after EMLP. Prevention of restenosis has been attempted with use of
      stents or medical therapy with topical application of mitomycin C and steroids with variable
      results.

      Recent studies have attempted to address this issue by using mucosal grafts to cover the
      exposed frontal bone after EMLP. These studies describe using free or pedicled mucosal grafts
      from various sites in the nasal cavity to cover the bare bone exposed after EMLP drill out
      procedure. Two studies reported results using free mucosal grafts to cover the exposed bone
      and showed encouraging results, with patency rates 95% and 100%. Another study using a
      pedicled flap based off the anterior ethmoidal artery showed no restenosis in 4 patients.
      These studies utilize mucosa mostly from the nasal septum at the region of the superior
      septectomy which would otherwise be discarded, but they do also report use of inferior
      turbinate mucosa harvesting. Though minimal morbidity related to mucosal harvest was
      reported, any mucosal harvest from sites other than the operative site has the potential for
      creating additional postoperative morbidity. In addition, use of mucosa from a diseased
      mucosal cavity may not be optimal. Reducing rates of restenosis and failure in EMLP will
      allow for improved outcomes following this procedure and may prevent progression to more
      invasive and extensive surgical procedures.

      This study will utilize a proprietary porcine intestinal submucosa graft Cook Biodesign™ ENT
      Repair graft to cover the exposed bone on the nasofrontal beak region following EMLP in order
      to evaluate its effects on mucosal healing and reduction of restenosis rates of the
      surgically augmented frontal sinus ostium after the Endoscopic Modified Lothrop Procedure.
      The Cook Biodesign™ ENT Repair for nasal mucosal replacement has been in use for sinonasal
      surgery since its Food and Drug Administration (FDA) approval in 2013. The Cook Biodesign™
      ENT Repair graft is FDA approved for prescription use to "separate tissue or structures
      compromised by surgical trauma, help control minimal bleeding, and act as an adjunct to aid
      in the natural healing process. The device is indicated for use where an open wound dressing
      material is required in the nasal and/or sinus cavities following nasal and/or sinus surgery
      where separation of tissues or structures is desired."

      The use of xenograft material in the method proposed in this submission has not been studied
      extensively. However, using free mucosal grafts or pedicled mucosal flaps after EMLP as
      previously discussed, have shown promise. The Cook Biodesign™ has been used preliminarily
      with patients in this proposed setting with good anecdotal results, including reduced
      crusting and good postoperative outcomes, however, its use has not yet been formally
      evaluated. The Cook Biodesign™ graft has several advantages over using native mucosal grafts:
      it is readily available and does not require harvest thus reducing operative times and
      potential morbidity from mucosa harvest sites, it is thinner than sinus mucosa and handled
      with ease, and it has tissue characteristics that promote wound healing. With the Cook
      Biodesign™, our hypothesis is that its use after EMLP surgery will allow for reduction of
      exposed bone in the sinonasal cavity and thus reduce inflammation, crusting and ultimately
      reduce restenosis and failure rates. Additionally, we hypothesize that reduction of crusting
      and inflammation will lead to improved patient reported symptom and quality of life scores on
      the Sinonasal Outcomes Test-22 (SNOT-22) questionnaire.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: Frontal sinus stenosis
time frame: 1 year
description: Evaluate the size of the frontal sinus outflow tract over one year after surgery
measure: Number of postoperative debridements
time frame: 1 year
description: Track the number of debridements required in the postoperative period
measure: Need for further surgical intervention
time frame: 1 year
description: Track if any further surgical procedures (in office or in operating room) that are required during postoperative period
measure: Number of postoperative infections
time frame: 1 year
description: Track the number of postoperative sinus infections, proven by culture, as well as the number of antibiotic courses required for treatment.
measure: Lund Kennedy Endoscopy Score
time frame: 1 year
description: Evaluation of the sinuses using nasal endoscopy and objective measurement using the validated Lund-Kennedy Endoscopy score
measure: SNOT-22 score
time frame: 1 year
description: Evaluation of patient quality of life using a validated questionnaire called the Sinonasal Outcome Test (SNOT) - 22.
arm group label: Control
arm group type: No Intervention
description: Subjects within the control arm will undergo the Draf III/Endoscopic Modified Lothrop procedure to address their sinus disease. At the end of the procedure, no Cook Biodesign Porcine intestinal submucosal graft will be used to cover the operative site. Light nasal packing will be placed in the nasal cavity for hemostasis. No placebo will be utilized.
arm group label: Cook Biodesign
arm group type: Experimental
description: Subjects within the experimental group will undergo the Draf III/Endoscopic Modified Lothrop procedure to address their sinus disease. At the end of the procedure, a small piece of Cook Biodesign porcine intestinal submucosal xenograft will be used to cover the exposed bone of the operative site along the frontal beak. It will be bolstered with light nasal packing to keep the graft in place during healing.
intervention type: Device
intervention name: Porcine Intestinal submucosal xenograft
description: Cook Biodesign ENT repair graft will be used in the experimental group to cover exposed bone in the sinonasal cavity as a result of the Draf III/endoscopic modified lothrop procedure.
arm group label: Cook Biodesign
other name: Cook Biodesign ENT Repair
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jeffrey D Suh, MD
role: Principal Investigator
affiliation: University of California Los Angeles, Department of Head and Neck Surgery
facility: 
country: United States
citation: Pleis JR, Lucas JW. Summary health statistics for U.S. adults: National Health Interview Survey, 2007. Vital Health Stat 10. 2009 May;(240):1-159.
PMID: 19645319
citation: Naidoo Y, Wen D, Bassiouni A, Keen M, Wormald PJ. Long-term results after primary frontal sinus surgery. Int Forum Allergy Rhinol. 2012 May-Jun;2(3):185-90. doi: 10.1002/alr.21015. Epub 2012 Jan 17.
PMID: 22253224
citation: Pynnonen MA, Davis MM. Extent of sinus surgery, 2000 to 2009: a population-based study. Laryngoscope. 2014 Apr;124(4):820-5. doi: 10.1002/lary.24335. Epub 2013 Oct 2.
PMID: 23900802
citation: Anderson P, Sindwani R. Safety and efficacy of the endoscopic modified Lothrop procedure: a systematic review and meta-analysis. Laryngoscope. 2009 Sep;119(9):1828-33. doi: 10.1002/lary.20565.
PMID: 19554631
citation: Wormald PJ. Salvage frontal sinus surgery: the endoscopic modified Lothrop procedure. Laryngoscope. 2003 Feb;113(2):276-83. doi: 10.1097/00005537-200302000-00015.
PMID: 12567082
citation: Tran KN, Beule AG, Singal D, Wormald PJ. Frontal ostium restenosis after the endoscopic modified Lothrop procedure. Laryngoscope. 2007 Aug;117(8):1457-62. doi: 10.1097/MLG.0b013e31806865be.
PMID: 17585278
citation: Ye T, Hwang PH, Huang Z, Huang Q, Xian J, Li C, Zhou B. Frontal ostium neo-osteogenesis and patency after Draf III procedure: a computer-assisted study. Int Forum Allergy Rhinol. 2014 Sep;4(9):739-44. doi: 10.1002/alr.21357. Epub 2014 Jul 30.
PMID: 25079177
citation: AlQahtani A, Bignami M, Terranova P, Digilio E, Basilico F, Abdulrahman S, Castelnuovo P. Newly designed double-vascularized nasoseptal flap to prevent restenosis after endoscopic modified Lothrop procedure (Draf III): laboratory investigation. Eur Arch Otorhinolaryngol. 2014 Nov;271(11):2951-5. doi: 10.1007/s00405-014-2961-2. Epub 2014 Mar 8.
PMID: 24609647
citation: Conger BT Jr, Riley K, Woodworth BA. The Draf III mucosal grafting technique: a prospective study. Otolaryngol Head Neck Surg. 2012 Apr;146(4):664-8. doi: 10.1177/0194599811432423. Epub 2012 Jan 6.
PMID: 22228601
citation: Hildenbrand T, Wormald PJ, Weber RK. Endoscopic frontal sinus drainage Draf type III with mucosal transplants. Am J Rhinol Allergy. 2012 Mar-Apr;26(2):148-51. doi: 10.2500/ajra.2012.26.3731.
PMID: 22487293
citation: Seyedhadi S, Mojtaba MA, Shahin B, Hoseinali K. The Draf III septal flap technique: a preliminary report. Am J Otolaryngol. 2013 Sep-Oct;34(5):399-402. doi: 10.1016/j.amjoto.2013.01.019. Epub 2013 Feb 26.
PMID: 23452383
citation: Wei CC, Sama A. What is the evidence for the use of mucosal flaps in Draf III procedures? Curr Opin Otolaryngol Head Neck Surg. 2014 Feb;22(1):63-7. doi: 10.1097/MOO.0000000000000023.
PMID: 24335916
responsible party type: Principal Investigator
investigator affiliation: University of California, Los Angeles
investigator full name: Jeffrey D. Suh
investigator title: Assistant Professor, Department of Head and Neck Surgery
mesh term: Sinusitis
mesh term: Frontal Sinusitis
sharing ipd: No