<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/NCT02260908</url>
  </required_header>
  <id_info>
    <org_study_id>OPT1-22-06-10</org_study_id>
    <nct_id>NCT02260908</nct_id>
  </id_info>
  <brief_title>OPtimal Timing of Thromboprophylaxis in Traumatic IntraCranial Haemorrhage - Pilot Study</brief_title>
  <acronym>OPTTICH</acronym>
  <official_title>OPTTICH Pilot Study - OPtimal Timing of Thromboprophylaxis in Traumatic IntraCranial Haemorrhage</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>McMaster University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Canadian Institutes of Health Research (CIHR)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>McMaster University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Victims of trauma with severe head injury who have bled into their brains are at high risk of&#xD;
      developing blood clots in their legs. These blood clots can break off and travel through the&#xD;
      bloodstream to the lungs, resulting in death. Blood thinners can be given to patients to&#xD;
      prevent blood clots from developing but this can leave patients at risk for additional&#xD;
      bleeding in the brain, causing further damage or death. The earlier blood thinners are&#xD;
      started, the more effective they are at preventing blood clots. In addition, some patients&#xD;
      with severe head injury who have bled into their brains will develop further bleeding even if&#xD;
      they do not receive blood thinners. Even though a growing body of research has shown that the&#xD;
      majority of bleeding in the brain stops within the first 24 hours after injury and that it is&#xD;
      safe to start blood thinners as early as 24 hours after injury, doctors are still waiting&#xD;
      longer than 4 days to start blood thinners in these patients over concerns of worsening&#xD;
      bleeding. In Canada, almost half of the patients with severe head injury do not receive blood&#xD;
      thinners until at least five days after injury. Delays in starting blood thinners appear to&#xD;
      put patients at increased risk of developing blood clots, unnecessarily. This study will&#xD;
      compare the benefits of starting low-molecular-weight heparin (LMWH), a type of blood&#xD;
      thinner, early (36 to 48 hours after injury) versus the current practice (waiting until the&#xD;
      6th day after being injured) in preventing blood clots in patients who have bled into their&#xD;
      brains after severe head injury. The investigators believe that starting LMWH earlier will be&#xD;
      more effective in preventing blood clots without worsening any bleeding when compared to&#xD;
      waiting to start blood thinners. This study is called OPTTICH (OPtimal timing of&#xD;
      Thromboprophylaxis in Traumatic IntraCranial Haemorrhage) and will be the largest Canadian&#xD;
      investigator-initiated randomized control trial on blood clot prevention in trauma patients&#xD;
      with severe head injury who have bled into their brains.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>October 2014</start_date>
  <completion_date type="Anticipated">September 2016</completion_date>
  <primary_completion_date type="Anticipated">September 2016</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proximal lower limb deep vein thrombosis (DVT) diagnosed by bilateral lower extremity compression ultrasound (US).</measure>
    <time_frame>Maximum of 60 days or until hospital discharge.</time_frame>
    <description>Ultrasounds will be performed within 72 hours of enrollment as well as twice weekly when in ICU and weekly thereafter. Non-compressibility of 1 or more proximal deep venous segments on compression US will be considered diagnostic. Each segment will be assessed as fully compressible, partially compressible, not compressible, or not well-visualized. All positive US will be recorded and stratified into above-knee (proximal DVT) or below-knee (distal DVT). Patients who have both proximal and distal DVT will be classified as having proximal DVT.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Non-intracranial bleeding</measure>
    <time_frame>Maximum of 60 days or until hospital discharge.</time_frame>
    <description>Non-intracranial bleeding events will be recorded and classified as either major or minor bleeding, according to a modified bleeding assessment tool adapted to our patient population.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pulmonary Embolism (PE)</measure>
    <time_frame>Maximum of 60 days or until hospital discharge.</time_frame>
    <description>Patients who develop clinical suspicion of PE will have a helical CT chest. Pulmonary embolism will be diagnosed by the presence of an intraluminal filling defect detected in either the main, lobar or segmental branches or the pulmonary artery. Patients with a high probability of PE on clinical grounds but with negative CT chest will undergo a ventilation-perfusion scan.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intracranial haemorrhage progression (IHP)</measure>
    <time_frame>Maximum of 60 days or until hospital discharge.</time_frame>
    <description>If a patient develops clinical evidence of neurological deterioration, an emergent head CT scan will be performed. The CT scan will be reviewed by the blinded attending neuroradiologist. A comparison to the previous CT scan will be made and assessed for evidence of IHP. Intracranial haemorrhage progression will be defined as either 1) the development of a new haematoma, 2) any enlargement of an existing haematoma by an attending neuroradiologist's CT report, or 3) any progression of haematoma by the Marshall Head CT Classification System.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">300</enrollment>
  <condition>Traumatic Intracranial Haemorrhage</condition>
  <arm_group>
    <arm_group_label>Early initiation of thromboprophylaxis</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Early initiation of thromboprophylaxis with Enoxaparin between 36-48 hours post-injury until day 5, followed by standard of care (DVT prophylaxis with Enoxaparin) starting on post-injury day 6.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Late initiation of thromboprophylaxis</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Initiation of placebo (normal saline) 36-48 hours post-injury until day 5, followed by standard of care (DVT prophylaxis with Enoxaparin) starting on post-injury day 6.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Enoxaparin</intervention_name>
    <description>Enoxaparin 30 mg subcutaneously twice daily for six doses, starting 36-48 hours post-traumatic injury.</description>
    <arm_group_label>Early initiation of thromboprophylaxis</arm_group_label>
    <other_name>Lovenox</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>0.9% normal saline in equal volume to active comparator given subcutaneously twice daily for six doses, starting 36-48 hours post-traumatic injury.</description>
    <arm_group_label>Late initiation of thromboprophylaxis</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Multi-system trauma patients referred to the trauma service with a non-progressing&#xD;
             tICH documented on 24-hour repeat head CT scan&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Unexpected to survive or remain in hospital &gt;72 hours&#xD;
&#xD;
          -  Known malignancy under active care at time of admission&#xD;
&#xD;
          -  Known DVT, PE or other condition requiring anticoagulation at time of admission&#xD;
&#xD;
          -  Coagulopathy (defined as international normalized ratio (INR) values &gt;1.5 times the&#xD;
             upper limit of normal, or partial thromboplastin time (PTT) values &gt;1.5 times the&#xD;
             upper limit of normal) at 24 hours after admission&#xD;
&#xD;
          -  Platelet count &lt;75 x 10^9/L at 24 hours after admission&#xD;
&#xD;
          -  Bilateral lower limb amputation&#xD;
&#xD;
          -  History of allergy to heparin or suspected or proven HIT&#xD;
&#xD;
          -  Limitation of life support or palliative care&#xD;
&#xD;
          -  Prior enrollment in this trial or currently in a confounding randomized trial&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Study drug (LMWH or placebo) not administered within 36-48 hours post-injury&#xD;
&#xD;
          -  Grade V liver or splenic injuries that have not received definitive care (e.g.&#xD;
             embolization, surgical intervention) within 36-48 hours after injury&#xD;
&#xD;
          -  Persistent intracranial pressure &gt;20 mm Hg&#xD;
&#xD;
          -  Spinal subdural haematoma or spinal epidural haematoma&#xD;
&#xD;
          -  Intracranial haemorrhage progression on 24-hour repeat CT scan&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>16 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Niv Sne, MD FRCSC</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hamilton Health Sciences/McMaster University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Niv Sne, MD FRCSC</last_name>
    <phone>905-527-4322</phone>
    <phone_ext>44665</phone_ext>
    <email>nivsne@yahoo.ca</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Timothy Rice, MD</last_name>
    <phone>905-527-4322</phone>
    <phone_ext>44665</phone_ext>
    <email>timothy.rice@medportal.ca</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Hamilton Health Sciences- General site</name>
      <address>
        <city>Hamilton</city>
        <state>Ontario</state>
        <zip>L8L 2X2</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Niv Sne, MD FRCSC</last_name>
      <phone>905-527-4322</phone>
      <phone_ext>44665</phone_ext>
      <email>nivsne@yahoo.ca</email>
    </contact>
    <investigator>
      <last_name>Niv Sne, MD FRCSC</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>April 2015</verification_date>
  <study_first_submitted>October 6, 2014</study_first_submitted>
  <study_first_submitted_qc>October 8, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 9, 2014</study_first_posted>
  <last_update_submitted>April 8, 2015</last_update_submitted>
  <last_update_submitted_qc>April 8, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">April 10, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>McMaster University</investigator_affiliation>
    <investigator_full_name>Niv Sne</investigator_full_name>
    <investigator_title>Dr. Niv Sne, Director of Trauma Research</investigator_title>
  </responsible_party>
  <keyword>Trauma</keyword>
  <keyword>Thromboprophylaxis</keyword>
  <keyword>Intracranial haemorrhage</keyword>
  <keyword>Deep vein thrombosis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Intracranial Hemorrhages</mesh_term>
    <mesh_term>Intracranial Hemorrhage, Traumatic</mesh_term>
    <mesh_term>Hemorrhage</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Enoxaparin</mesh_term>
  </intervention_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/NCT02260908
org study id: OPT1-22-06-10
nct id: NCT02260908
lead sponsor: 
collaborator: 
has dmc: No
Victims of trauma with severe head injury who have bled into their brains are at high risk of
      developing blood clots in their legs. These blood clots can break off and travel through the
      bloodstream to the lungs, resulting in death. Blood thinners can be given to patients to
      prevent blood clots from developing but this can leave patients at risk for additional
      bleeding in the brain, causing further damage or death. The earlier blood thinners are
      started, the more effective they are at preventing blood clots. In addition, some patients
      with severe head injury who have bled into their brains will develop further bleeding even if
      they do not receive blood thinners. Even though a growing body of research has shown that the
      majority of bleeding in the brain stops within the first 24 hours after injury and that it is
      safe to start blood thinners as early as 24 hours after injury, doctors are still waiting
      longer than 4 days to start blood thinners in these patients over concerns of worsening
      bleeding. In Canada, almost half of the patients with severe head injury do not receive blood
      thinners until at least five days after injury. Delays in starting blood thinners appear to
      put patients at increased risk of developing blood clots, unnecessarily. This study will
      compare the benefits of starting low-molecular-weight heparin (LMWH), a type of blood
      thinner, early (36 to 48 hours after injury) versus the current practice (waiting until the
      6th day after being injured) in preventing blood clots in patients who have bled into their
      brains after severe head injury. The investigators believe that starting LMWH earlier will be
      more effective in preventing blood clots without worsening any bleeding when compared to
      waiting to start blood thinners. This study is called OPTTICH (OPtimal timing of
      Thromboprophylaxis in Traumatic IntraCranial Haemorrhage) and will be the largest Canadian
      investigator-initiated randomized control trial on blood clot prevention in trauma patients
      with severe head injury who have bled into their brains.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Proximal lower limb deep vein thrombosis (DVT) diagnosed by bilateral lower extremity compression ultrasound (US).
time frame: Maximum of 60 days or until hospital discharge.
description: Ultrasounds will be performed within 72 hours of enrollment as well as twice weekly when in ICU and weekly thereafter. Non-compressibility of 1 or more proximal deep venous segments on compression US will be considered diagnostic. Each segment will be assessed as fully compressible, partially compressible, not compressible, or not well-visualized. All positive US will be recorded and stratified into above-knee (proximal DVT) or below-knee (distal DVT). Patients who have both proximal and distal DVT will be classified as having proximal DVT.
measure: Non-intracranial bleeding
time frame: Maximum of 60 days or until hospital discharge.
description: Non-intracranial bleeding events will be recorded and classified as either major or minor bleeding, according to a modified bleeding assessment tool adapted to our patient population.
measure: Pulmonary Embolism (PE)
time frame: Maximum of 60 days or until hospital discharge.
description: Patients who develop clinical suspicion of PE will have a helical CT chest. Pulmonary embolism will be diagnosed by the presence of an intraluminal filling defect detected in either the main, lobar or segmental branches or the pulmonary artery. Patients with a high probability of PE on clinical grounds but with negative CT chest will undergo a ventilation-perfusion scan.
measure: Intracranial haemorrhage progression (IHP)
time frame: Maximum of 60 days or until hospital discharge.
description: If a patient develops clinical evidence of neurological deterioration, an emergent head CT scan will be performed. The CT scan will be reviewed by the blinded attending neuroradiologist. A comparison to the previous CT scan will be made and assessed for evidence of IHP. Intracranial haemorrhage progression will be defined as either 1) the development of a new haematoma, 2) any enlargement of an existing haematoma by an attending neuroradiologist's CT report, or 3) any progression of haematoma by the Marshall Head CT Classification System.
arm group label: Early initiation of thromboprophylaxis
arm group type: Active Comparator
description: Early initiation of thromboprophylaxis with Enoxaparin between 36-48 hours post-injury until day 5, followed by standard of care (DVT prophylaxis with Enoxaparin) starting on post-injury day 6.
arm group label: Late initiation of thromboprophylaxis
arm group type: Placebo Comparator
description: Initiation of placebo (normal saline) 36-48 hours post-injury until day 5, followed by standard of care (DVT prophylaxis with Enoxaparin) starting on post-injury day 6.
intervention type: Drug
intervention name: Enoxaparin
description: Enoxaparin 30 mg subcutaneously twice daily for six doses, starting 36-48 hours post-traumatic injury.
arm group label: Early initiation of thromboprophylaxis
other name: Lovenox
intervention type: Other
intervention name: Placebo
description: 0.9% normal saline in equal volume to active comparator given subcutaneously twice daily for six doses, starting 36-48 hours post-traumatic injury.
arm group label: Late initiation of thromboprophylaxis
criteria: 
gender: All
minimum age: 16 Years
maximum age: N/A
healthy volunteers: No
last name: Niv Sne, MD FRCSC
role: Principal Investigator
affiliation: Hamilton Health Sciences/McMaster University
last name: Niv Sne, MD FRCSC
phone: 905-527-4322
phone ext: 44665
email: nivsne@yahoo.ca
last name: Timothy Rice, MD
phone: 905-527-4322
phone ext: 44665
email: timothy.rice@medportal.ca
facility: 
status: Recruiting
contact: 
investigator: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: McMaster University
investigator full name: Niv Sne
investigator title: Dr. Niv Sne, Director of Trauma Research
mesh term: Intracranial Hemorrhages
mesh term: Intracranial Hemorrhage, Traumatic
mesh term: Hemorrhage
mesh term: Enoxaparin