<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/NCT03282695</url>
  </required_header>
  <id_info>
    <org_study_id>BCV-OZO-2016-01</org_study_id>
    <nct_id>NCT03282695</nct_id>
  </id_info>
  <brief_title>Ozone Therapy in Patients on Waiting List for Surgery Due to Disc Herniation: Prospective, Post-authorization Study</brief_title>
  <acronym>O3HDCIRUGIA</acronym>
  <official_title>Ozone Therapy in Patients on Waiting List for Surgery Due to Disc Herniation: Prospective, Post-authorization Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bernardino Clavo, MD, PhD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Servicio Canario de Salud</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Red de Investigación en Servicios de Salud en Enfermedades Crónicas</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Instituto de Salud Carlos III</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Colegio Oficial de Médicos de Las Palmas</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Dr. Negrin University Hospital</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>
      The main objective of this study is to estimate the cost-effectiveness of ozone therapy in&#xD;
      patients on the waiting list for surgery due to disc herniation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A cohort study (patients on the waiting list for surgery due to herniated disc) will be&#xD;
      carried out, to which the treatment with ozone will be offered, without giving up the planned&#xD;
      surgical intervention.&#xD;
&#xD;
      The main objective of this prospective, post-authorization follow-up study is to estimate the&#xD;
      cost-effectiveness of ozone therapy (compared to standard care) in patients with disc&#xD;
      herniation waiting for surgery (by microdiscectomy). Besides utilities of patients with disc&#xD;
      herniation on a waiting list for surgery will be estimated, social/economic burden of disc&#xD;
      herniation will be quantified and a decision aid will be developed and applied.&#xD;
&#xD;
      The main outcome measures are &quot;Direct hospital cost&quot;, &quot;Percentage of executed surgeries&quot; and&#xD;
      &quot;Change in sciatic pain&quot;. In addition, data on health-related quality of life and resource&#xD;
      utilization will be collected which will permit to estimate the incremental&#xD;
      cost-effectiveness ratio (ICER), comparing incremental costs and quality adjusted life years&#xD;
      (QALY).&#xD;
&#xD;
      The variables will be collected at the beginning, on the day of treatment and at 1, 3, 6, 12&#xD;
      and 24 months. The enrollment period will be 24 months. The follow-up period will be 24&#xD;
      months.&#xD;
&#xD;
      The results of the study will allow a better understanding of the value of ozone therapy in&#xD;
      the management of patients on the waiting list for herniated disc surgery. In addition, it&#xD;
      will contribute to the development of a more patient-centered health system.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">March 9, 2018</start_date>
  <completion_date type="Anticipated">December 31, 2022</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2022</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Direct Hospital Cost for patients included on waiting list for surgery due to disc herniation.</measure>
    <time_frame>24 months</time_frame>
    <description>Euros</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of surgeries finally performed.</measure>
    <time_frame>24 months</time_frame>
    <description>Percentage of surgeries performed after enrollment</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from Baseline in sciatic pain at 12 months</measure>
    <time_frame>12 months</time_frame>
    <description>Visual Analogic Scale (VAS)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from Baseline in sciatic pain at 24 months</measure>
    <time_frame>24 months</time_frame>
    <description>Visual Analogic Scale (VAS)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in sciatic pain at 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>Visual Analogic Scale (VAS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in lumbar pain at 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>Visual Analogic Scale (VAS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in lumbar pain at 12 months</measure>
    <time_frame>12 months</time_frame>
    <description>Visual Analogic Scale (VAS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in lumbar pain at 24 months</measure>
    <time_frame>24 months</time_frame>
    <description>Visual Analogic Scale (VAS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of hospital stay days</measure>
    <time_frame>24 months</time_frame>
    <description>Number of hospital stay days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Restriction of everyday activities</measure>
    <time_frame>24 months</time_frame>
    <description>Spanish version of Roland-Morris questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life by 12-Item Short Form Survey (SF-12)</measure>
    <time_frame>24 months</time_frame>
    <description>SF-12 questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life by the five-level version of the EuroQol five-dimensional (EQ-5D-5L) questionnaire</measure>
    <time_frame>24 months</time_frame>
    <description>EQ-5D-5L questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Loss of labour productivity</measure>
    <time_frame>24 months</time_frame>
    <description>Off work days (if applicable)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to resume normal activity</measure>
    <time_frame>24 months</time_frame>
    <description>Days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Direct sanitary and non-sanitary costs incurred out of hospital.</measure>
    <time_frame>24 months</time_frame>
    <description>Euros</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse effects</measure>
    <time_frame>24 months</time_frame>
    <description>Number of serious adverse effects</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time from inclusion on waiting list for surgery to completion of the procedure.</measure>
    <time_frame>24 months</time_frame>
    <description>Days</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">80</enrollment>
  <condition>Lumbar Herniated Disc</condition>
  <arm_group>
    <arm_group_label>Surgery</arm_group_label>
    <description>Patients on waiting list for surgery (by discectomy/microdiscectomy) who reject ozone infiltration during waiting time.&#xD;
These patients will receive standard pain treatment until the planned surgery.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ozone</arm_group_label>
    <description>Patients on waiting list for surgery (by discectomy/microdiscectomy) who accept treatment by ozone infiltration during waiting time.&#xD;
These patients will be treated primarily by ozone therapy: Infiltration of intradiscal O3/O2 + foraminal infiltration of O3/O2 + corticoid + anesthetic.&#xD;
These patients will receive standard pain treatment until the planned surgery.</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Adults with symptomatic lumbar herniated disc in whom conservative medical management has&#xD;
        failed and: 1) in whom discectomy or microdiscectomy is indicated, 2) have been included in&#xD;
        surgery waiting list by the Neurosurgery Department, 3) who meet criteria for potential&#xD;
        benefit with ozone therapy and 4) who accept participating in the study by&#xD;
        answering/filling in the specific study questionnaires (wether they accept or not the ozone&#xD;
        therapy).&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosed with a herniated and not calcified lumbar disc that presents as: not&#xD;
             migrated protrusion and/or extrusion.&#xD;
&#xD;
          -  Evaluated and diagnosed by the Neurosurgery Department, having been chosen as an&#xD;
             appropriate candidate for surgery consisting in discectomy or microdiscectomy, after&#xD;
             meeting the following two criteria: 1) Sciatic pain, with a visual analogue scale&#xD;
             (VAS) intensity ≥ 5, despite 6 weeks of conservative management, wether it exists&#xD;
             lumbar pain or not and 2) Radiating pain that matches the MRI image showing one or&#xD;
             more herniated discs (not to be considered those patients with two herniated discs and&#xD;
             symptoms attributable to only one of the herniated discs).&#xD;
&#xD;
          -  Included in the surgery waiting list for a discectomy or microdiscectomy.&#xD;
&#xD;
          -  Patients who have signed and dated the study 's specific informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who do not meet all the inclusion criteria.&#xD;
&#xD;
          -  Calcified and/or migrated herniated disc, and/or with a severe neurological deficits&#xD;
             (cauda equine syndrome).&#xD;
&#xD;
          -  Herniated disc with surgical indication of laminectomy and/or arthrodesis (massive&#xD;
             extrusion, sign of instability or other conditions under the neurosurgeon judgment).&#xD;
&#xD;
          -  Relevant clinical paresis that does not improve despite 6 weeks of full conservative&#xD;
             management (patients with severe pain and mild paresis that only shows up in the&#xD;
             physical exam are not to be excluded, but those who present with paresis as the main&#xD;
             symptom -&quot;clinically relevant&quot;- must be).&#xD;
&#xD;
          -  Simultaneous symptomatic cervical or dorsal herniated discs.&#xD;
&#xD;
          -  Previous lumbar spine surgery.&#xD;
&#xD;
          -  Concomitant spine conditions that may be causing symptoms or have indication for&#xD;
             surgery (such as fractures or tumors).&#xD;
&#xD;
          -  Known allergy to ozone.&#xD;
&#xD;
          -  Those who are uncapable to fill in the scales used to measure variables in the study,&#xD;
             like the visual analogue scale (VAS), Roland-Morris and SF-12 questionnaires.&#xD;
&#xD;
          -  Those who are unable or do not wish to fulfill the study 's protocol (answer questions&#xD;
             to collect the data).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bernardino Clavo, MD, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Dr. Negrín University Hospital, Las Palmas, Spain</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Pedro G. Serrano-Aguilar, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Servicio de Evaluación. Servicio Canario de Salud. Spain</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Renata Linertová, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fundación Canaria de Investigación Sanitaria (FUNCANIS)</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Adam Szolna, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Dr. Negrín University Hospital, Las Palmas. Spain</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Dr. Negrin University Hospital</name>
      <address>
        <city>Las Palmas De Gran Canaria</city>
        <state>Las Palmas</state>
        <zip>35019</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <link>
    <url>http://www3.gobiernodecanarias.org/sanidad/scs/content/4c7be1f8-a10e-11e6-a33b-757951c5b2fa/Informe_Ozonoterapia_SESCS%202016.pdf</url>
    <description>Report (June 2016) about Ozone therapy in disc herniation, from the Health Technology Assessment (HTA) Unit, Canary Health Service, Spain</description>
  </link>
  <reference>
    <citation>Magalhaes FN, Dotta L, Sasse A, Teixera MJ, Fonoff ET. Ozone therapy as a treatment for low back pain secondary to herniated disc: a systematic review and meta-analysis of randomized controlled trials. Pain Physician. 2012 Mar-Apr;15(2):E115-29.</citation>
    <PMID>22430658</PMID>
  </reference>
  <reference>
    <citation>Sherman J, Cauthen J, Schoenberg D, Burns M, Reaven NL, Griffith SL. Economic impact of improving outcomes of lumbar discectomy. Spine J. 2010 Feb;10(2):108-16. doi: 10.1016/j.spinee.2009.08.453. Epub 2009 Oct 12. Erratum In: Spine J. 2010 May;10(5):A8.</citation>
    <PMID>19819761</PMID>
  </reference>
  <reference>
    <citation>Tosteson AN, Skinner JS, Tosteson TD, Lurie JD, Andersson GB, Berven S, Grove MR, Hanscom B, Blood EA, Weinstein JN. The cost effectiveness of surgical versus nonoperative treatment for lumbar disc herniation over two years: evidence from the Spine Patient Outcomes Research Trial (SPORT). Spine (Phila Pa 1976). 2008 Sep 1;33(19):2108-15. doi: 10.1097/brs.0b013e318182e390.</citation>
    <PMID>18777603</PMID>
  </reference>
  <results_reference>
    <citation>Hansson E, Hansson T. The cost-utility of lumbar disc herniation surgery. Eur Spine J. 2007 Mar;16(3):329-37. doi: 10.1007/s00586-006-0131-y. Epub 2006 May 9.</citation>
    <PMID>16683121</PMID>
  </results_reference>
  <results_reference>
    <citation>Luhmann D, Burkhardt-Hammer T, Borowski C, Raspe H. Minimally invasive surgical procedures for the treatment of lumbar disc herniation. GMS Health Technol Assess. 2005 Nov 15;1:Doc07.</citation>
    <PMID>21289928</PMID>
  </results_reference>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>September 12, 2017</study_first_submitted>
  <study_first_submitted_qc>September 13, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 14, 2017</study_first_posted>
  <last_update_submitted>April 1, 2022</last_update_submitted>
  <last_update_submitted_qc>April 1, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 4, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Dr. Negrin University Hospital</investigator_affiliation>
    <investigator_full_name>Bernardino Clavo, MD, PhD</investigator_full_name>
    <investigator_title>MD. PhD</investigator_title>
  </responsible_party>
  <keyword>Disc Herniation</keyword>
  <keyword>Lumbar Herniated Disc</keyword>
  <keyword>Ozone Therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Intervertebral Disc Displacement</mesh_term>
    <mesh_term>Hernia</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/NCT03282695
org study id: BCV-OZO-2016-01
nct id: NCT03282695
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The main objective of this study is to estimate the cost-effectiveness of ozone therapy in
      patients on the waiting list for surgery due to disc herniation.
A cohort study (patients on the waiting list for surgery due to herniated disc) will be
      carried out, to which the treatment with ozone will be offered, without giving up the planned
      surgical intervention.

      The main objective of this prospective, post-authorization follow-up study is to estimate the
      cost-effectiveness of ozone therapy (compared to standard care) in patients with disc
      herniation waiting for surgery (by microdiscectomy). Besides utilities of patients with disc
      herniation on a waiting list for surgery will be estimated, social/economic burden of disc
      herniation will be quantified and a decision aid will be developed and applied.

      The main outcome measures are "Direct hospital cost", "Percentage of executed surgeries" and
      "Change in sciatic pain". In addition, data on health-related quality of life and resource
      utilization will be collected which will permit to estimate the incremental
      cost-effectiveness ratio (ICER), comparing incremental costs and quality adjusted life years
      (QALY).

      The variables will be collected at the beginning, on the day of treatment and at 1, 3, 6, 12
      and 24 months. The enrollment period will be 24 months. The follow-up period will be 24
      months.

      The results of the study will allow a better understanding of the value of ozone therapy in
      the management of patients on the waiting list for herniated disc surgery. In addition, it
      will contribute to the development of a more patient-centered health system.
observational model: Cohort
time perspective: Prospective
measure: Direct Hospital Cost for patients included on waiting list for surgery due to disc herniation.
time frame: 24 months
description: Euros
measure: Percentage of surgeries finally performed.
time frame: 24 months
description: Percentage of surgeries performed after enrollment
measure: Change from Baseline in sciatic pain at 12 months
time frame: 12 months
description: Visual Analogic Scale (VAS)
measure: Change from Baseline in sciatic pain at 24 months
time frame: 24 months
description: Visual Analogic Scale (VAS)
measure: Change from Baseline in sciatic pain at 6 months
time frame: 6 months
description: Visual Analogic Scale (VAS)
measure: Change from Baseline in lumbar pain at 6 months
time frame: 6 months
description: Visual Analogic Scale (VAS)
measure: Change from Baseline in lumbar pain at 12 months
time frame: 12 months
description: Visual Analogic Scale (VAS)
measure: Change from Baseline in lumbar pain at 24 months
time frame: 24 months
description: Visual Analogic Scale (VAS)
measure: Number of hospital stay days
time frame: 24 months
description: Number of hospital stay days
measure: Restriction of everyday activities
time frame: 24 months
description: Spanish version of Roland-Morris questionnaire
measure: Quality of life by 12-Item Short Form Survey (SF-12)
time frame: 24 months
description: SF-12 questionnaire
measure: Quality of life by the five-level version of the EuroQol five-dimensional (EQ-5D-5L) questionnaire
time frame: 24 months
description: EQ-5D-5L questionnaire
measure: Loss of labour productivity
time frame: 24 months
description: Off work days (if applicable)
measure: Time to resume normal activity
time frame: 24 months
description: Days
measure: Direct sanitary and non-sanitary costs incurred out of hospital.
time frame: 24 months
description: Euros
measure: Adverse effects
time frame: 24 months
description: Number of serious adverse effects
measure: Time from inclusion on waiting list for surgery to completion of the procedure.
time frame: 24 months
description: Days
arm group label: Surgery
description: Patients on waiting list for surgery (by discectomy/microdiscectomy) who reject ozone infiltration during waiting time.
These patients will receive standard pain treatment until the planned surgery.
arm group label: Ozone
description: Patients on waiting list for surgery (by discectomy/microdiscectomy) who accept treatment by ozone infiltration during waiting time.
These patients will be treated primarily by ozone therapy: Infiltration of intradiscal O3/O2 + foraminal infiltration of O3/O2 + corticoid + anesthetic.
These patients will receive standard pain treatment until the planned surgery.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Bernardino Clavo, MD, PhD
role: Study Chair
affiliation: Dr. Negrín University Hospital, Las Palmas, Spain
last name: Pedro G. Serrano-Aguilar, MD, PhD
role: Study Director
affiliation: Servicio de Evaluación. Servicio Canario de Salud. Spain
last name: Renata Linertová, MD, PhD
role: Principal Investigator
affiliation: Fundación Canaria de Investigación Sanitaria (FUNCANIS)
last name: Adam Szolna, MD, PhD
role: Principal Investigator
affiliation: Dr. Negrín University Hospital, Las Palmas. Spain
facility: 
country: Spain
url: http://www3.gobiernodecanarias.org/sanidad/scs/content/4c7be1f8-a10e-11e6-a33b-757951c5b2fa/Informe_Ozonoterapia_SESCS%202016.pdf
description: Report (June 2016) about Ozone therapy in disc herniation, from the Health Technology Assessment (HTA) Unit, Canary Health Service, Spain
citation: Magalhaes FN, Dotta L, Sasse A, Teixera MJ, Fonoff ET. Ozone therapy as a treatment for low back pain secondary to herniated disc: a systematic review and meta-analysis of randomized controlled trials. Pain Physician. 2012 Mar-Apr;15(2):E115-29.
PMID: 22430658
citation: Sherman J, Cauthen J, Schoenberg D, Burns M, Reaven NL, Griffith SL. Economic impact of improving outcomes of lumbar discectomy. Spine J. 2010 Feb;10(2):108-16. doi: 10.1016/j.spinee.2009.08.453. Epub 2009 Oct 12. Erratum In: Spine J. 2010 May;10(5):A8.
PMID: 19819761
citation: Tosteson AN, Skinner JS, Tosteson TD, Lurie JD, Andersson GB, Berven S, Grove MR, Hanscom B, Blood EA, Weinstein JN. The cost effectiveness of surgical versus nonoperative treatment for lumbar disc herniation over two years: evidence from the Spine Patient Outcomes Research Trial (SPORT). Spine (Phila Pa 1976). 2008 Sep 1;33(19):2108-15. doi: 10.1097/brs.0b013e318182e390.
PMID: 18777603
citation: Hansson E, Hansson T. The cost-utility of lumbar disc herniation surgery. Eur Spine J. 2007 Mar;16(3):329-37. doi: 10.1007/s00586-006-0131-y. Epub 2006 May 9.
PMID: 16683121
citation: Luhmann D, Burkhardt-Hammer T, Borowski C, Raspe H. Minimally invasive surgical procedures for the treatment of lumbar disc herniation. GMS Health Technol Assess. 2005 Nov 15;1:Doc07.
PMID: 21289928
responsible party type: Sponsor-Investigator
investigator affiliation: Dr. Negrin University Hospital
investigator full name: Bernardino Clavo, MD, PhD
investigator title: MD. PhD
mesh term: Intervertebral Disc Displacement
mesh term: Hernia
sharing ipd: No