<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/NCT04480047</url>
  </required_header>
  <id_info>
    <org_study_id>DVAL19033</org_study_id>
    <nct_id>NCT04480047</nct_id>
  </id_info>
  <brief_title>Feasibility Study to Assess Outcomes of Immediately Inserted and Restored Dental Implants Using Tetranite</brief_title>
  <official_title>A Prospective Human Clinical Study to Assess Primary Stability and Change in Stability By Resonance Frequency Analysis of Immediately Inserted and Restored Dental Implants Using Tetranite Stabilization Material</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>RevBio</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Dentsply Sirona Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>RevBio</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this Pilot Study is to demonstrate the safety and efficacy of the use of&#xD;
      Tetranite-Stabilization Material (TN-SM) in delivering enhanced stability to immediately&#xD;
      restored dental implants inserted into fresh extraction sockets, with both clinical and&#xD;
      patient-related successful outcomes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The purpose of the present study is to evaluate the safety and efficacy of a single stage&#xD;
      approach using Tetranite Stabilization Material (TN-SM). The purpose of the efficacy&#xD;
      component of this study is a composite comprising: (1) First - To demonstrate and evaluate&#xD;
      the ability of TN-SM to achieve immediate implant stabilization in sites otherwise unable to&#xD;
      provide primary stability without requiring the delay in treatment imposed by the current&#xD;
      multi-staged standard-of-care method; (2) Second - To demonstrate and evaluate the ability of&#xD;
      TN-SM to achieve sufficient short-term stabilization of implants, as measured by resonance&#xD;
      frequency analysis, as the device undergoes initial resorption and replacement with new bone;&#xD;
      (3) Third - To demonstrate the ability of TN-SM to aid in the maintenance of alveolar bone,&#xD;
      without buccal plate collapse and loss of crestal bone height; and Fourth (4) - To&#xD;
      demonstrate and evaluate the ability of a TN-SM stabilized implant to achieve implant success&#xD;
      (after criteria of Buser, et. al 1) after 12 months while the device undergoes significant&#xD;
      resorption, facilitates osteoconduction, and replacement with new bone. In addition to the&#xD;
      Primary Endpoints of establishing the Safety and Efficacy of Implant Stabilization and&#xD;
      Implant Success throughout the initial 12 months of post-functional loading, the study also&#xD;
      assesses several secondary endpoints over the course of the study and one-year follow-up, as&#xD;
      outlined in the sections below. These include assessment of incidence, duration, and severity&#xD;
      of adverse effects and events; assessment of increasing implant stiffness; assessment of bone&#xD;
      levels, bone volumetric changes; patient satisfaction surveys, and assessment of periodontal&#xD;
      and peri-implant health integral to implant success.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 15, 2020</start_date>
  <completion_date type="Actual">January 25, 2023</completion_date>
  <primary_completion_date type="Actual">January 25, 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Single arm, objective performance criteria study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Implant Stabilization by Resonance Frequency Analysis</measure>
    <time_frame>12-month</time_frame>
    <description>The primary endpoint is sufficient bone-to-implant interfacial stiffness post-placement of the implant stabilized by TN-SM, whereby, sufficient bone-to-implant interfacial stiffness is measured by Resonance Frequency Analysis (RFA) expressed as mean Implant Stability Quotient (ISQ, 0-100 scale, where higher is better) at 1-year post TN-SM device and implant placement. For the study to be considered successful, the lower bound of the one-sided 97.5% confidence interval for the mean ISQ should exceed the clinical threshold of 60.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Implant Stabilization by Resonance Frequency Analysis</measure>
    <time_frame>15 minutes, 3 months, and 7 months</time_frame>
    <description>Sufficient bone-to-implant interfacial stiffness measured by Resonance Frequency Analysis (RFA) expressed as Implant Stability Quotient (ISQ, 0-100 scale, where higher ISQ is better) at 15 minutes, 1 week, 1 month, 3 months, and 7 months post-implant placement. For each timepoint to be considered successful, the lower bound of the one-sided 97.5% confidence interval for the mean ISQ should exceed the clinical threshold of 60;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Device Related Adverse Events</measure>
    <time_frame>12-month</time_frame>
    <description>Low incidence, severity and duration of device-related adverse events throughout the 12-month post-implant placement follow-up period;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Implant Stabilization by Forward Torque Assessment</measure>
    <time_frame>15 minutes</time_frame>
    <description>Immediate implant stabilization demonstrated by no rotation of the implant subjected to forward torque of 20 Ncm at 15 minutes after application of the TN-SM;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Implant Success (Composite Measure)</measure>
    <time_frame>12-month</time_frame>
    <description>Composite measure of implant success throughout the 12-month post-loading follow-up period consisting of:&#xD;
Presence of the implant at its site of implantation; and,&#xD;
Absence of a recurrent peri-implant infection with suppuration; and,&#xD;
No perceptible mobility upon palpation;&#xD;
Absence of encapsulation, defined as continuous radiolucency around the implant in a periapical radiograph;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bone Level Maintenance</measure>
    <time_frame>12-month</time_frame>
    <description>Crestal bone level maintenance assessed by analysis of two-dimensional periapical radiographic records showing no more than a 1.0mm loss of height throughout the 12-month post-loading follow-up period;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Volume Loss</measure>
    <time_frame>12-month</time_frame>
    <description>Dimensional changes in bone volume will be evaluated: before tooth extraction, and through the 12-month post-loading follow-up period. CBCT data will be used to perform these assessments; Peri-implant tissue health demonstrated by direct measurement around the implant at 12 months after placement of the implant as compared to existing conditions in the oral cavity near adjacent teeth to the implant site and to baseline around the implant at 3 months post placement</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient Satisfaction</measure>
    <time_frame>12-month</time_frame>
    <description>Subject satisfaction using the VAS scale (0-100) for pain where 0 is no pain, esthetic outcome and function.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">15</enrollment>
  <condition>Adhesive Dental</condition>
  <arm_group>
    <arm_group_label>Tetranite Stabilized Dental Implants with Provisional Crown</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Extraction of maxillary anterior teeth followed by immediate insertion and stabilization of dental implants with Tetranite in otherwise non-stable sites. A provisional crown will also be inserted during this surgery.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Tetranite Stabilization Material (TN-SM)</intervention_name>
    <description>Dental adhesive for increased implant stabilization</description>
    <arm_group_label>Tetranite Stabilized Dental Implants with Provisional Crown</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Screening Inclusion Criteria&#xD;
&#xD;
               -  Subjects must have voluntarily signed the informed consent form before any study&#xD;
                  related procedures;&#xD;
&#xD;
               -  Subjects must be males or females who are a minimum of 20 years of age;&#xD;
&#xD;
               -  Subjects who require a single anterior maxillary tooth extraction and desire a&#xD;
                  replacement with a dental implant and immediate temporary crown. Candidate&#xD;
                  subjects may require more than one extraction, and all sites will be considered&#xD;
                  for inclusion in the study;&#xD;
&#xD;
               -  Subjects must have opposing dentition (natural teeth, fixed or removable&#xD;
                  restorations);&#xD;
&#xD;
               -  Subjects must be committed to the study and the required follow-up visits;&#xD;
&#xD;
               -  Subjects must be ASA I or ASA II;&#xD;
&#xD;
               -  Subjects who present with a sound bony housing with a visible buccal plate&#xD;
                  evident at the crest and fenestrations or dehiscences limited to &lt;5.0mm diameter&#xD;
                  on a cone beam CT&#xD;
&#xD;
               -  • There must be sufficient bone height crestal to critical anatomical structures,&#xD;
                  i.e., the piriform foramen, and maxillary sinus, to safely place a dental implant&#xD;
                  within the bone contours. Extraction sockets should be able to accommodate an&#xD;
                  implant &gt; 9.0mm in length;&#xD;
&#xD;
               -  Anatomical conditions must be present to allow an implant crown restoration to be&#xD;
                  placed at the candidate site, e.g., sufficient interocclusal space, incisal&#xD;
                  Class1 or Class 2 Div 1 relation, appropriate angulation of the ridge, etc.&#xD;
&#xD;
               -  Extraction Site Enrollment Inclusion Criteria&#xD;
&#xD;
               -  There is at least 2mm of apical bone below the apex of the extraction socket for&#xD;
                  positive seating of the implant;&#xD;
&#xD;
               -  Any implant site in which placement of the selected implant leaves an HDD &gt; 2mm&#xD;
                  in the buccal direction between the implant surface and the labial plate at the&#xD;
                  most coronal aspect of the extraction socket.&#xD;
&#xD;
          -  Extraction Site Enrollment Inclusion Criteria&#xD;
&#xD;
               -  There is at least 2mm of apical bone below the apex of the extraction socket for&#xD;
                  positive seating of the implant;&#xD;
&#xD;
               -  Any implant site in which placement of the selected implant leaves an HDD &gt; 2mm&#xD;
                  in the buccal direction between the implant surface and the labial plate at the&#xD;
                  most coronal aspect of the extraction socket.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Screening Exclusion Criteria&#xD;
&#xD;
               -  Subjects with a systemic disease or condition affecting a major organ system that&#xD;
                  would preclude dental implant surgery (e.g., malignant neoplasm or chemotherapy&#xD;
                  in the past 6 months, uncontrolled diabetes, major infection, Cushing's syndrome,&#xD;
                  metabolic bone disease, immunosuppression, blood dyscrasias, healing bone&#xD;
                  fracture, myocardial infarction or cerebrovascular accident within the last six&#xD;
                  months, etc.);&#xD;
&#xD;
               -  Subjects with any contraindications for oral surgical procedures (e.g.&#xD;
                  scleroderma, etc.);&#xD;
&#xD;
               -  Subjects with mucosal diseases (e.g. erosive lichen planus, mucous membrane&#xD;
                  pemphigoid, erythema multiforme, etc.) in the localized area around the study&#xD;
                  implant site;&#xD;
&#xD;
               -  Subjects with bone diseases or conditions (e.g. Paget's disease, fibrous&#xD;
                  dysplasia, history of osteomyelitis, etc.) in the region of the potential study&#xD;
                  implant site;&#xD;
&#xD;
               -  Subjects with a history of local radiation therapy in the head/neck area or&#xD;
                  osteonecrosis of the jaws;&#xD;
&#xD;
               -  Subjects receiving, or having a recent or long-term history (&gt; 5 years) of&#xD;
                  receiving, oral anti-osteoclastic agents [e.g., bisphosphonates, Fosamax® and&#xD;
                  Prolia® (denosumab); Forsteo® (teriparatide), strontium ranelate, etc.], or&#xD;
                  anti-angiogenesis factors;&#xD;
&#xD;
               -  Subjects receiving or having a recent history of receiving (within 1 year)&#xD;
                  intravenous anti-osteoclastic agents (e.g. Ibandronate, Boniva®; Zoledronate,&#xD;
                  Zometa®).&#xD;
&#xD;
               -  Subjects who have major active substance abuse problems (e.g., alcoholism, opiate&#xD;
                  addiction, methamphetamine abuse, etc.);&#xD;
&#xD;
               -  Subjects who are pregnant or intending to become pregnant during the duration of&#xD;
                  the study;&#xD;
&#xD;
               -  Subjects who are heavy smokers (defined as &gt;10 cigarettes per day or &gt;1 cigar per&#xD;
                  day or equivalent of electronic cigarette vaping) or chew tobacco;&#xD;
&#xD;
               -  Subjects with inadequate oral hygiene or who are unmotivated for adequate home&#xD;
                  care;&#xD;
&#xD;
               -  Subjects who have physical or mental handicaps that would interfere with the&#xD;
                  ability to perform adequate oral hygiene;&#xD;
&#xD;
               -  Subjects who have undergone administration of any investigational device within&#xD;
                  30 days of enrollment in the study;&#xD;
&#xD;
               -  Subjects who are allergic or otherwise sensitive to any materials likely&#xD;
                  encountered during the course of the study (e.g. titanium, suture materials,&#xD;
                  local anesthetics);&#xD;
&#xD;
               -  Subjects with conditions or circumstances, which, in the opinion of the&#xD;
                  Investigator, would prevent completion of study participation or interfere with&#xD;
                  analysis of study results, such as history of non-compliance or unreliability.&#xD;
&#xD;
          -  Extraction Site Enrollment Exclusion Criteria&#xD;
&#xD;
               -  Any site into which the implant is not or cannot be placed during the same visit&#xD;
                  as the extraction&#xD;
&#xD;
               -  Any implant site where there is a dehiscence or fenestration of buccal or lingual&#xD;
                  plates of bone greater than 5mm in any direction;&#xD;
&#xD;
               -  Any implant site in which placement of the selected implant leaves an HDD greater&#xD;
                  than 5mm in any direction between the implant surface and the most coronal aspect&#xD;
                  of the osteotomy;&#xD;
&#xD;
               -  Any site which provides primary implant stability after seating as demonstrated&#xD;
                  by insertion torque of greater than or equal to 15Ncm;&#xD;
&#xD;
               -  Any implant site where, during the osteotomy preparation, a submarginal&#xD;
                  perforation develops&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Grayson Allen, MBA</last_name>
    <role>Study Chair</role>
    <affiliation>RevBio</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Norton Implants</name>
      <address>
        <city>London</city>
        <zip>W1G 7JD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <reference>
    <citation>Cochran DL, Jones A, Sugita R, Brown MC, Guda T, Prasad H, Ong JL, Pollack A, Kay GW. Immediate Dental Implant Stabilization in a Canine Model Using a Novel Mineral-Organic Adhesive: 4-Month Results. Int J Oral Maxillofac Implants. 2020 Jan/Feb;35(1):39-51. doi: 10.11607/jomi.7891.</citation>
    <PMID>31923288</PMID>
  </reference>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>July 17, 2020</study_first_submitted>
  <study_first_submitted_qc>July 17, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 21, 2020</study_first_posted>
  <last_update_submitted>August 7, 2023</last_update_submitted>
  <last_update_submitted_qc>August 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 9, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>dental implant</keyword>
  <keyword>stabilization</keyword>
  <keyword>resonance frequency analysis (RFA)</keyword>
  <keyword>bone adhesive</keyword>
  <keyword>ridge height</keyword>
  <keyword>implant success</keyword>
  <keyword>primary stability</keyword>
  <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/NCT04480047
org study id: DVAL19033
nct id: NCT04480047
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: Yes
The aim of this Pilot Study is to demonstrate the safety and efficacy of the use of
      Tetranite-Stabilization Material (TN-SM) in delivering enhanced stability to immediately
      restored dental implants inserted into fresh extraction sockets, with both clinical and
      patient-related successful outcomes.
The purpose of the present study is to evaluate the safety and efficacy of a single stage
      approach using Tetranite Stabilization Material (TN-SM). The purpose of the efficacy
      component of this study is a composite comprising: (1) First - To demonstrate and evaluate
      the ability of TN-SM to achieve immediate implant stabilization in sites otherwise unable to
      provide primary stability without requiring the delay in treatment imposed by the current
      multi-staged standard-of-care method; (2) Second - To demonstrate and evaluate the ability of
      TN-SM to achieve sufficient short-term stabilization of implants, as measured by resonance
      frequency analysis, as the device undergoes initial resorption and replacement with new bone;
      (3) Third - To demonstrate the ability of TN-SM to aid in the maintenance of alveolar bone,
      without buccal plate collapse and loss of crestal bone height; and Fourth (4) - To
      demonstrate and evaluate the ability of a TN-SM stabilized implant to achieve implant success
      (after criteria of Buser, et. al 1) after 12 months while the device undergoes significant
      resorption, facilitates osteoconduction, and replacement with new bone. In addition to the
      Primary Endpoints of establishing the Safety and Efficacy of Implant Stabilization and
      Implant Success throughout the initial 12 months of post-functional loading, the study also
      assesses several secondary endpoints over the course of the study and one-year follow-up, as
      outlined in the sections below. These include assessment of incidence, duration, and severity
      of adverse effects and events; assessment of increasing implant stiffness; assessment of bone
      levels, bone volumetric changes; patient satisfaction surveys, and assessment of periodontal
      and peri-implant health integral to implant success.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Single arm, objective performance criteria study
primary purpose: Treatment
masking: None (Open Label)
measure: Implant Stabilization by Resonance Frequency Analysis
time frame: 12-month
description: The primary endpoint is sufficient bone-to-implant interfacial stiffness post-placement of the implant stabilized by TN-SM, whereby, sufficient bone-to-implant interfacial stiffness is measured by Resonance Frequency Analysis (RFA) expressed as mean Implant Stability Quotient (ISQ, 0-100 scale, where higher is better) at 1-year post TN-SM device and implant placement. For the study to be considered successful, the lower bound of the one-sided 97.5% confidence interval for the mean ISQ should exceed the clinical threshold of 60.
measure: Implant Stabilization by Resonance Frequency Analysis
time frame: 15 minutes, 3 months, and 7 months
description: Sufficient bone-to-implant interfacial stiffness measured by Resonance Frequency Analysis (RFA) expressed as Implant Stability Quotient (ISQ, 0-100 scale, where higher ISQ is better) at 15 minutes, 1 week, 1 month, 3 months, and 7 months post-implant placement. For each timepoint to be considered successful, the lower bound of the one-sided 97.5% confidence interval for the mean ISQ should exceed the clinical threshold of 60;
measure: Device Related Adverse Events
time frame: 12-month
description: Low incidence, severity and duration of device-related adverse events throughout the 12-month post-implant placement follow-up period;
measure: Implant Stabilization by Forward Torque Assessment
time frame: 15 minutes
description: Immediate implant stabilization demonstrated by no rotation of the implant subjected to forward torque of 20 Ncm at 15 minutes after application of the TN-SM;
measure: Implant Success (Composite Measure)
time frame: 12-month
description: Composite measure of implant success throughout the 12-month post-loading follow-up period consisting of:
Presence of the implant at its site of implantation; and,
Absence of a recurrent peri-implant infection with suppuration; and,
No perceptible mobility upon palpation;
Absence of encapsulation, defined as continuous radiolucency around the implant in a periapical radiograph;
measure: Bone Level Maintenance
time frame: 12-month
description: Crestal bone level maintenance assessed by analysis of two-dimensional periapical radiographic records showing no more than a 1.0mm loss of height throughout the 12-month post-loading follow-up period;
measure: Volume Loss
time frame: 12-month
description: Dimensional changes in bone volume will be evaluated: before tooth extraction, and through the 12-month post-loading follow-up period. CBCT data will be used to perform these assessments; Peri-implant tissue health demonstrated by direct measurement around the implant at 12 months after placement of the implant as compared to existing conditions in the oral cavity near adjacent teeth to the implant site and to baseline around the implant at 3 months post placement
measure: Patient Satisfaction
time frame: 12-month
description: Subject satisfaction using the VAS scale (0-100) for pain where 0 is no pain, esthetic outcome and function.
arm group label: Tetranite Stabilized Dental Implants with Provisional Crown
arm group type: Experimental
description: Extraction of maxillary anterior teeth followed by immediate insertion and stabilization of dental implants with Tetranite in otherwise non-stable sites. A provisional crown will also be inserted during this surgery.
intervention type: Device
intervention name: Tetranite Stabilization Material (TN-SM)
description: Dental adhesive for increased implant stabilization
arm group label: Tetranite Stabilized Dental Implants with Provisional Crown
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Grayson Allen, MBA
role: Study Chair
affiliation: RevBio
facility: 
country: United Kingdom
citation: Cochran DL, Jones A, Sugita R, Brown MC, Guda T, Prasad H, Ong JL, Pollack A, Kay GW. Immediate Dental Implant Stabilization in a Canine Model Using a Novel Mineral-Organic Adhesive: 4-Month Results. Int J Oral Maxillofac Implants. 2020 Jan/Feb;35(1):39-51. doi: 10.11607/jomi.7891.
PMID: 31923288
responsible party type: Sponsor
sharing ipd: No