<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/NCT03828136</url>
  </required_header>
  <id_info>
    <org_study_id>CT-17-001</org_study_id>
    <nct_id>NCT03828136</nct_id>
  </id_info>
  <brief_title>Novum Vitrium® Cervical Cage in Anterior Cervical Discectomy and Fusion</brief_title>
  <official_title>Safety and Effectiveness of Novum Vitrium® Cervical Cage in Anterior Cervical Discectomy and Fusion. A Randomized, Controlled, Non-inferiority, Pivotal Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bio2 Technologies</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>MCRA</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Bio2 Technologies</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      A prospective, multicenter, randomized, concurrently controlled, noninferiority clinical&#xD;
      trial to compare the safety and effectiveness of instrumented Bio2 Vitrium Cervical Interbody&#xD;
      Device in anterior cervical discectomy and fusion (ACDF) with structural allograft bone and&#xD;
      local autologous bone graft in treating patients with a symptomatic degenerative cervical&#xD;
      disc disease at one level from C3/C4 to C7/T1.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study will evaluate if Bio2 Vitrium® Cervical Interbody Device (VCIBD) is non-inferior to&#xD;
      allograft cage in single-level ACDF with the use of local autologous bone. VCIBD is a&#xD;
      restorable cervical interbody cage for the treatment of fusion, following discectomy, of the&#xD;
      cervical spine from C3/C4 disc space to the C7/T1 disc space. The material used to&#xD;
      manufacture the implant is 13-93 bioactive glass, which is a silicate-based material as&#xD;
      described in ASTM F1538-03(R2017). The implant has high porosity and strength and does not&#xD;
      contain any biological material or constitute a combination product. The device has a central&#xD;
      lumen for packing with autograft. VCIBD is intended to be used with a supplemental fixation&#xD;
      system.&#xD;
&#xD;
      The device, when placed between the vertebrae, provides mechanical stability and prevents&#xD;
      subsidence prior to bone ingrowth. It restores and maintains the intervertebral space during&#xD;
      the fusion process. The porosity and material characteristics provide an osteoconductive&#xD;
      matrix that supports bone ingrowth. Additional stabilization is provided by supplemental&#xD;
      fixation using anterior cervical plate. The implant incorporates a central lumen, which&#xD;
      allows for the cage to be packed with autogenous bone graft.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Sponsor business decision&#xD;
  </why_stopped>
  <start_date type="Actual">April 24, 2019</start_date>
  <completion_date type="Actual">March 21, 2022</completion_date>
  <primary_completion_date type="Actual">March 21, 2022</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>
    <intervention_model_description>A total of 168 patients will be randomized in 7:2 ratio to Investigational (n=130) and Control arms (n=38).</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants who have achieved of radiologic fusion assessed by roentgenographic examination.</measure>
    <time_frame>12 months</time_frame>
    <description>Successful fusion is based on meeting the roentgenographic examination criteria showing the evidence of: bridging trabecular bone between the involved motion segments; translation motion &lt;3mm; and angular motion ≤2°.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Neck Disability Index (NDI) with a response greater than or equal to 15 from baseline.</measure>
    <time_frame>12 months</time_frame>
    <description>NDI consists of ten items addressing function activities, pain intensity, concentration, and headache.It has a continuous various with a range from 0 (best) to 100 (worse). The effectiveness endpoint is the difference between the baseline value and the follow-up (12 month) value.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with neurological success.</measure>
    <time_frame>12 months</time_frame>
    <description>Neurological success is a binary outcome as follows:&#xD;
Maintenance or improvement of the neurological status;&#xD;
Worsening of the neurological status.&#xD;
Worsening of the neurological status is defined as permanent new neurologic damage or permanent new nerve root injury related to the surgically treated level, defined as one or more:&#xD;
Permanent decrease in one or more grades of motor strength compared to baseline;&#xD;
Permanent new sensory deficit (paresthesia or anesthesia) in a specific cervical nerve root distribution.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants who have completed follow-up up to month 12 without Secondary Surgical Intervention (SSI).</measure>
    <time_frame>12 months</time_frame>
    <description>Identified as the absence of revision, removal, reoperation, or supplemental fixation at the index level</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Measurement of Pain at neck and at arm and shoulder as assessed by Visual Analog Scale</measure>
    <time_frame>6, 12, and 24 months</time_frame>
    <description>Neck pain and arm/shoulder pain as measured by the Visual Analog Scale (VAS) on the scale from 0 (no pain) to 100 (worst imaginable pain)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life assessed by 36-Item Short Form Health Survey Version 2 (SF-36v2)</measure>
    <time_frame>6, 12, and 24 months</time_frame>
    <description>The SF-36v2 Health Survey is a 36-item instrument for measuring health status and outcomes. It yields an eight-scale profile score from the following eight health concepts: physical functioning, role limitations due to physical health problems, bodily pain, general health, vitality (energy/fatigue), social functioning, role limitations due to emotional problems, and general mental health (psychological distress and psychological well being). In addition, two composites scores are constructed using factorial modeling, one from physical health composite score (PCS) and one for mental health composite score (MCS).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life assessed by EuroQoL Health Related Quality of Life - 5 Dimensions - 3 Levels (EQ-5D-3L)</measure>
    <time_frame>6, 12, and 24 months</time_frame>
    <description>The EQ-5D-3L is a standardized instrument used as a measure of health outcomes. It contains questions in 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and provides a simple descriptive profile and single index for health status preference. In addition, there is a Visual Analog Scale (VAS). The VAS is the participant's rating of their health on a scale of 0 &quot;worst imaginable health state&quot; to 100 &quot;best imaginable health state&quot;.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measurement of the use of Pain Medication for Cervical Spine.</measure>
    <time_frame>6, 12, and 24 months</time_frame>
    <description>The use of prescription and OTC pain medication for cervical spine-related pain will be recorded in addition to the use of opioids on study-specific logs.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measurement of Patient Satisfaction: patients to rate their satisfaction</measure>
    <time_frame>6, 12, and 24 months</time_frame>
    <description>Developed based on IDE spine studies. It asks patients to rate their satisfaction with their treatment (6 choices from &quot;Very Satisfied&quot; to &quot;Very Dissatisfied&quot;), and question regarding every day activities and their ability to complete them. There are 5 choices from &quot;Definitely&quot; to &quot;Definitely Not&quot;.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">25</enrollment>
  <condition>Symptomatic Cervical Disc Disease</condition>
  <arm_group>
    <arm_group_label>ACDF with Novum Vitrium® Cervical Interbody Device</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A resorbable cervical interbody cage.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ACDF with Allograft</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Structural allograft made from structural corticocancellous allograft bone.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Novum Vitrium® Cervical Interbody Device</intervention_name>
    <description>For spinal fusion procedure at one level (C3 to T1) of the cervical spine.</description>
    <arm_group_label>ACDF with Novum Vitrium® Cervical Interbody Device</arm_group_label>
    <other_name>Novum Vitrium® Cervical Cage</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Allograft Ring or Block</intervention_name>
    <description>Standard of Care</description>
    <arm_group_label>ACDF with Allograft</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Symptomatic cervical disc disease (SCDD) in the one vertebral level between C3/C4 to&#xD;
             C7/T1, defined as neck or arm (radicular) pain, or functional or neurological deficit&#xD;
             and correlated with radiculopathy or myelopathy or radiographic confirmation (by CT,&#xD;
             MRI, x-ray, etc.) of any of the following:&#xD;
&#xD;
               -  Herniated nucleus pulposus;&#xD;
&#xD;
               -  Spondylosis (defined by the presence of osteophytes); or&#xD;
&#xD;
               -  Loss of disc height.&#xD;
&#xD;
          2. Requires only one cervical vertebral level to be surgically treated, confirmed&#xD;
             radiologically by Xray, CT, or MRI and correlated with neurologic examination prior to&#xD;
             enrollment;&#xD;
&#xD;
          3. Age between 22 and 70 years (inclusive);&#xD;
&#xD;
          4. Skeletally mature patients;&#xD;
&#xD;
          5. Failed at least 6 weeks of conservative treatment (e.g. medication, physical therapy),&#xD;
             or exhibit progressive symptoms or signs of spinal cord/nerve root compression with&#xD;
             continued non-operative care;&#xD;
&#xD;
          6. Neck Disability Index (NDI) Questionnaire score of at least 30 (on a scale from 0 to&#xD;
             100);&#xD;
&#xD;
          7. Able to read and Understand all documents used in this study, including the Informed&#xD;
             Consent and patient-reported outcome questionnaires;&#xD;
&#xD;
          8. Understand and read English at elementary level;&#xD;
&#xD;
          9. Patient must understand and sign the Informed Consent document that has been approved&#xD;
             by the Ethics committee, Institutional review Board and the FDA.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. More than one vertebral level requiring treatment, confirmed radiologically by X-ray,&#xD;
             CT, or MRI&#xD;
&#xD;
          2. Cervical instability;&#xD;
&#xD;
          3. Prior fusion surgery at any cervical vertebral level;&#xD;
&#xD;
          4. Prior surgery at the level to be treated with the exception of surgery that does not&#xD;
             require the use of hardware and/or the treatment of facet disease;&#xD;
&#xD;
          5. Severe facet disease;&#xD;
&#xD;
          6. Clinically compromised vertebral bodies at the affected level(s) due to current or&#xD;
             past trauma&#xD;
&#xD;
          7. Neck or arm pain of unknown etiology;&#xD;
&#xD;
          8. Osteoporosis, osteopenia, Paget's disease, osteomalacia or any other metabolic bone&#xD;
             disease;&#xD;
&#xD;
             a. Osteoporosis is defined as history of fragility fracture and Dexa (DXA) T-score &lt;&#xD;
             -2.5 or QCT T-score &lt; 80mg/cubic cm. History of a fragility fracture requires that a&#xD;
             DXA scan or QCT scan is completed&#xD;
&#xD;
          9. Pregnant or interested in becoming pregnant in the next 2 years;&#xD;
&#xD;
         10. Active systemic or local infection;&#xD;
&#xD;
         11. History of severe allergy or anaphylaxis especially to titanium, polyethylene, cobalt,&#xD;
             chromium or molybdenum;&#xD;
&#xD;
         12. Taking medications or any drug known to potentially interfere with bone/soft tissue&#xD;
             healing (e.g., steroids, bisphosphonates);&#xD;
&#xD;
         13. Rheumatoid arthritis or another autoimmune disease that affects musculoskeletal&#xD;
             system;&#xD;
&#xD;
         14. Acquired immune deficiency syndrome (AIDS) or an AIDS-related complex;&#xD;
&#xD;
         15. Active malignancy or history of invasive malignancy within the last five years, except&#xD;
             for superficial basal cell carcinoma or squamous cell carcinoma of the skin that has&#xD;
             been definitely treated; patients with carcinoma in situ of the uterine cervix treated&#xD;
             definitely more than 1 year prior to enrollment may enter the study;&#xD;
&#xD;
         16. Neuromuscular disorders such as muscular dystrophy, spinal muscular atrophy, and&#xD;
             amyotrophic lateral sclerosis;&#xD;
&#xD;
         17. Pre-existent neurologic or mental disorder which would preclude accurate evaluation&#xD;
             and followup (i.e. Alzheimer's disease, Parkinson's disease, unstable psychiatric&#xD;
             disorder with hallucinations and/or delusions or schizophrenia);&#xD;
&#xD;
         18. Substance use disorder categorized as moderate to severe as defined in DSM-V;&#xD;
&#xD;
         19. Mental/Psychiatric disorder as defined in DSM-V;&#xD;
&#xD;
         20. Alcohol abuse disorder categorized as moderate to severe as defined in DSM-V;&#xD;
&#xD;
         21. Current Smokers;&#xD;
&#xD;
         22. Use of bone growth stimulator in the region of the cervical spine within the past 30&#xD;
             days;&#xD;
&#xD;
         23. Participation in other investigational device or drug clinical trials within 30 days&#xD;
             of surgery;&#xD;
&#xD;
         24. Prisoners;&#xD;
&#xD;
         25. Morbid obesity, defined as body mass index (&quot;BMI&quot;) &gt; 40;&#xD;
&#xD;
         26. Type 1 diabetes mellitus requiring daily insulin therapy unless there is documentation&#xD;
             of a recent A1c (within 6 months) of less than 7.1 or Type 2 diabetes where the&#xD;
             clinical presentation precludes the patient from having surgery;&#xD;
&#xD;
         27. Involved in litigation related to the spine;&#xD;
&#xD;
         28. On workers compensation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>22 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Orthopaedic Education and Research Institute</name>
      <address>
        <city>Orange</city>
        <state>California</state>
        <zip>92868</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hartford Hospital</name>
      <address>
        <city>Hartford</city>
        <state>Connecticut</state>
        <zip>06102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Indiana Spine Group</name>
      <address>
        <city>Carmel</city>
        <state>Indiana</state>
        <zip>46032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Orthopaedic Institute of Western Kentucky</name>
      <address>
        <city>Paducah</city>
        <state>Kentucky</state>
        <zip>42001</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Upstate Medical University</name>
      <address>
        <city>Syracuse</city>
        <state>New York</state>
        <zip>13210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>M3-Emerging Medical Research</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27704</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arise Medical Center</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78746</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>January 25, 2019</study_first_submitted>
  <study_first_submitted_qc>January 31, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 4, 2019</study_first_posted>
  <last_update_submitted>March 30, 2022</last_update_submitted>
  <last_update_submitted_qc>March 30, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 7, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Cervical Disc Disease</keyword>
  <keyword>ACDF</keyword>
  <keyword>Single-level</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Intervertebral Disc Displacement</mesh_term>
    <mesh_term>Intervertebral Disc Degeneration</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03828136
org study id: CT-17-001
nct id: NCT03828136
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
A prospective, multicenter, randomized, concurrently controlled, noninferiority clinical
      trial to compare the safety and effectiveness of instrumented Bio2 Vitrium Cervical Interbody
      Device in anterior cervical discectomy and fusion (ACDF) with structural allograft bone and
      local autologous bone graft in treating patients with a symptomatic degenerative cervical
      disc disease at one level from C3/C4 to C7/T1.
The study will evaluate if Bio2 Vitrium® Cervical Interbody Device (VCIBD) is non-inferior to
      allograft cage in single-level ACDF with the use of local autologous bone. VCIBD is a
      restorable cervical interbody cage for the treatment of fusion, following discectomy, of the
      cervical spine from C3/C4 disc space to the C7/T1 disc space. The material used to
      manufacture the implant is 13-93 bioactive glass, which is a silicate-based material as
      described in ASTM F1538-03(R2017). The implant has high porosity and strength and does not
      contain any biological material or constitute a combination product. The device has a central
      lumen for packing with autograft. VCIBD is intended to be used with a supplemental fixation
      system.

      The device, when placed between the vertebrae, provides mechanical stability and prevents
      subsidence prior to bone ingrowth. It restores and maintains the intervertebral space during
      the fusion process. The porosity and material characteristics provide an osteoconductive
      matrix that supports bone ingrowth. Additional stabilization is provided by supplemental
      fixation using anterior cervical plate. The implant incorporates a central lumen, which
      allows for the cage to be packed with autogenous bone graft.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: A total of 168 patients will be randomized in 7:2 ratio to Investigational (n=130) and Control arms (n=38).
primary purpose: Treatment
masking: Single (Participant)
measure: Number of participants who have achieved of radiologic fusion assessed by roentgenographic examination.
time frame: 12 months
description: Successful fusion is based on meeting the roentgenographic examination criteria showing the evidence of: bridging trabecular bone between the involved motion segments; translation motion <3mm; and angular motion ≤2°.
measure: Change in Neck Disability Index (NDI) with a response greater than or equal to 15 from baseline.
time frame: 12 months
description: NDI consists of ten items addressing function activities, pain intensity, concentration, and headache.It has a continuous various with a range from 0 (best) to 100 (worse). The effectiveness endpoint is the difference between the baseline value and the follow-up (12 month) value.
measure: Number of participants with neurological success.
time frame: 12 months
description: Neurological success is a binary outcome as follows:
Maintenance or improvement of the neurological status;
Worsening of the neurological status.
Worsening of the neurological status is defined as permanent new neurologic damage or permanent new nerve root injury related to the surgically treated level, defined as one or more:
Permanent decrease in one or more grades of motor strength compared to baseline;
Permanent new sensory deficit (paresthesia or anesthesia) in a specific cervical nerve root distribution.
measure: Number of participants who have completed follow-up up to month 12 without Secondary Surgical Intervention (SSI).
time frame: 12 months
description: Identified as the absence of revision, removal, reoperation, or supplemental fixation at the index level
measure: Measurement of Pain at neck and at arm and shoulder as assessed by Visual Analog Scale
time frame: 6, 12, and 24 months
description: Neck pain and arm/shoulder pain as measured by the Visual Analog Scale (VAS) on the scale from 0 (no pain) to 100 (worst imaginable pain)
measure: Quality of Life assessed by 36-Item Short Form Health Survey Version 2 (SF-36v2)
time frame: 6, 12, and 24 months
description: The SF-36v2 Health Survey is a 36-item instrument for measuring health status and outcomes. It yields an eight-scale profile score from the following eight health concepts: physical functioning, role limitations due to physical health problems, bodily pain, general health, vitality (energy/fatigue), social functioning, role limitations due to emotional problems, and general mental health (psychological distress and psychological well being). In addition, two composites scores are constructed using factorial modeling, one from physical health composite score (PCS) and one for mental health composite score (MCS).
measure: Quality of Life assessed by EuroQoL Health Related Quality of Life - 5 Dimensions - 3 Levels (EQ-5D-3L)
time frame: 6, 12, and 24 months
description: The EQ-5D-3L is a standardized instrument used as a measure of health outcomes. It contains questions in 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and provides a simple descriptive profile and single index for health status preference. In addition, there is a Visual Analog Scale (VAS). The VAS is the participant's rating of their health on a scale of 0 "worst imaginable health state" to 100 "best imaginable health state".
measure: Measurement of the use of Pain Medication for Cervical Spine.
time frame: 6, 12, and 24 months
description: The use of prescription and OTC pain medication for cervical spine-related pain will be recorded in addition to the use of opioids on study-specific logs.
measure: Measurement of Patient Satisfaction: patients to rate their satisfaction
time frame: 6, 12, and 24 months
description: Developed based on IDE spine studies. It asks patients to rate their satisfaction with their treatment (6 choices from "Very Satisfied" to "Very Dissatisfied"), and question regarding every day activities and their ability to complete them. There are 5 choices from "Definitely" to "Definitely Not".
arm group label: ACDF with Novum Vitrium® Cervical Interbody Device
arm group type: Experimental
description: A resorbable cervical interbody cage.
arm group label: ACDF with Allograft
arm group type: Active Comparator
description: Structural allograft made from structural corticocancellous allograft bone.
intervention type: Device
intervention name: Novum Vitrium® Cervical Interbody Device
description: For spinal fusion procedure at one level (C3 to T1) of the cervical spine.
arm group label: ACDF with Novum Vitrium® Cervical Interbody Device
other name: Novum Vitrium® Cervical Cage
intervention type: Device
intervention name: Allograft Ring or Block
description: Standard of Care
arm group label: ACDF with Allograft
criteria: 
gender: All
minimum age: 22 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Intervertebral Disc Displacement
mesh term: Intervertebral Disc Degeneration