<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/NCT03754114</url>
  </required_header>
  <id_info>
    <org_study_id>BOOST3</org_study_id>
    <secondary_id>U01NS099046</secondary_id>
    <nct_id>NCT03754114</nct_id>
  </id_info>
  <brief_title>Brain Oxygen Optimization in Severe TBI, Phase 3</brief_title>
  <acronym>BOOST3</acronym>
  <official_title>Brain Oxygen Optimization in Severe TBI (BOOST3): A Comparative Effectiveness Study to Test the Efficacy of a Prescribed Treatment Protocol Based on Monitoring the Partial Pressure of Brain Tissue Oxygen.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Michigan</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Neurological Disorders and Stroke (NINDS)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Washington</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Pennsylvania</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Pittsburgh</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Medical University of South Carolina</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Michigan</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      BOOST3 is a randomized clinical trial to determine the comparative effectiveness of two&#xD;
      strategies for monitoring and treating patients with traumatic brain injury (TBI) in the&#xD;
      intensive care unit (ICU). The study will determine the safety and efficacy of a strategy&#xD;
      guided by treatment goals based on both intracranial pressure (ICP) and brain tissue oxygen&#xD;
      (PbtO2) as compared to a strategy guided by treatment goals based on ICP monitoring alone.&#xD;
      Both of these alternative strategies are used in standard care. It is unknown if one is more&#xD;
      effective than the other. In both strategies the monitoring and goals help doctors adjust&#xD;
      treatments including the kinds and doses of medications and the amount of intravenous fluids&#xD;
      given, ventilator (breathing machine) settings, need for blood transfusions, and other&#xD;
      medical care. The results of this study will help doctors discover if one of these methods is&#xD;
      more safe and effective.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      BOOST3 is a randomized clinical trial to determine the comparative effectiveness of two&#xD;
      strategies for monitoring and treating patients with traumatic brain injury (TBI) in the&#xD;
      intensive care unit (ICU).&#xD;
&#xD;
      When a person has a TBI, their injured brain can swell over a period of hours or days. If the&#xD;
      brain swells too much, the pressure in the skull increases and becomes dangerous, causing&#xD;
      further injury to the brain. To try to prevent this, doctors usually insert a device, an ICP&#xD;
      monitor, into the brain through a hole in the skull of people with severe TBI. An ICP monitor&#xD;
      measures the pressure inside the skull. Most doctors agree that it is important to measure&#xD;
      and prevent high ICP. Patients with injured brains also suffer additional injury to the brain&#xD;
      if the amount of oxygen in the brain gets too low. Some doctors also insert a second device,&#xD;
      a PbtO2 monitor, in the brain through the same or a second hole in the skull to measure brain&#xD;
      tissue oxygen. A PbtO2 monitor measures how much oxygen is in a small area of the brain near&#xD;
      the tip of the monitor. Other doctors think this is unnecessary and unhelpful. Both&#xD;
      monitoring devices are approved by the US Food and Drug Administration (FDA) and Health&#xD;
      Canada for patients with TBI. Both are commonly used. The ICP and PbtO2 goals guided by these&#xD;
      monitors are used to help doctors adjust their treatment choices. Treatments include kinds&#xD;
      and doses of medications and the amount of intravenous fluids given, ventilator (breathing&#xD;
      machine) settings, need for blood transfusions, and other medical care. Each of these&#xD;
      treatment decisions is intended to improve outcomes. However, each treatment decision also&#xD;
      involves potential risks. Different treatment decisions may result in different risks. This&#xD;
      study will also help doctors better understand these risks. This study is funded by the&#xD;
      National Institutes of Health because it answers questions important to the care of patients&#xD;
      with TBI.&#xD;
&#xD;
      This study is a two-arm, single-blind, randomized, controlled, phase III, multi-center trial&#xD;
      of ICU monitoring and treatment strategies for patients with severe TBI. It will compare the&#xD;
      efficacy of ICU care guided by PbtO2 and ICP monitoring versus monitoring of ICP alone in the&#xD;
      first 5 days after injury. Only subjects who have severe TBI and require invasive monitoring,&#xD;
      according to Brain Trauma Foundation (BTF) and American College of Surgeons-Trauma Quality&#xD;
      Improvement (ACS TQIP) guidelines, will be enrolled. All participants in this study will have&#xD;
      both ICP monitors and PbtO2 monitors. Half of the participants will be randomized to an arm&#xD;
      that includes treatment informed by PbtO2 and ICP, and half will be randomized to an arm that&#xD;
      treats only ICP.&#xD;
&#xD;
      The PbtO2 values of those in the ICP only arm will be masked, so that the treating physicians&#xD;
      will not be guided by PbtO2 information. Participants in the PbtO2 and ICP arm will have&#xD;
      PbtO2 monitored and low measurements treated. Treatments to address physiological goals in&#xD;
      both arms will follow a clinical standardization plan. Participants will be followed for 6&#xD;
      months and occurrence of serious adverse events or death will be recorded. Participants will&#xD;
      have a follow-up interview to assess their level of recovery approximately 6 months post&#xD;
      injury.&#xD;
&#xD;
      To reduce the likelihood of imbalance of important prognostic factors between groups, a&#xD;
      covariate-adjusted randomization scheme will be used in this study. Adjustment variables are&#xD;
      clinical site and probability of a poor outcome as defined by the IMPACT core model.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 28, 2019</start_date>
  <completion_date type="Anticipated">November 1, 2027</completion_date>
  <primary_completion_date type="Anticipated">November 1, 2027</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>The outcomes assessors will be blinded to the treatment assignment of the participant.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Glasgow Outcome Scale-Extended (GOS-E)</measure>
    <time_frame>6 months</time_frame>
    <description>The Glasgow Outcome Scale-Extended (GOS-E) is a global scale for functional outcome, in which higher scores indicate better outcomes. The GOS-E rates patient status into one of eight categories. A GOS-E score of 1 indicates death, 2 indicates a vegetative state, 3 or 4 indicates severe disability, 5 or 6 indicates moderate disability, and 7 or 8 indicates good recovery. The categories of severe disability, moderate disability and good recovery are subdivided into a lower and upper category. All injury related disabilities are assessed.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Survival</measure>
    <time_frame>At discharge from hospital, an average of 19 days</time_frame>
    <description>Survival at discharge from hospital</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total Brain Hypoxia Exposure</measure>
    <time_frame>Inclusive of up to 5 days of study intervention</time_frame>
    <description>The cumulative area on the time versus brain tissue oxygenation (PbtO2) curve in which PbtO2 is less than 20 mmHg.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognition: Rey Auditory Verbal Learning Test</measure>
    <time_frame>6 months</time_frame>
    <description>A measure of verbal learning and memory.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognition: Trail Making Test Part A+B</measure>
    <time_frame>6 months</time_frame>
    <description>A measure of attention, visual-motor tracking and executive functioning.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Emotional Health: Rivermead Post-Concussion Symptom Questionnaire</measure>
    <time_frame>6 months</time_frame>
    <description>A measure of the presence and severity of post-concussion somatic, cognitive, and emotional symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Emotional Health: Brief Symptom Inventory 18</measure>
    <time_frame>6 months</time_frame>
    <description>A measure of psychological distress and psychiatric disorders.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Emotional Health: Satisfaction with Life Scale</measure>
    <time_frame>6 months</time_frame>
    <description>A measure of global cognitive judgments of one's life satisfaction.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional Status Exam</measure>
    <time_frame>6 months</time_frame>
    <description>Change in the activities of every day life as a function of a sudden event or illness</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">1094</enrollment>
  <condition>Brain Injuries, Traumatic</condition>
  <arm_group>
    <arm_group_label>ICP only</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>ICP guided management strategy: Care in the ICU of research participants randomized to this arm will be guided by a monitoring and treatment strategy in which doctors try to prevent high intracranial pressure (ICP) caused by a swollen brain. This strategy is one of two alternative strategies that is currently used in standard care of patients with traumatic brain injury.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ICP + PbtO2</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>ICP + PbtO2 guided management strategy: Care in the ICU of research participants randomized to this arm will be guided by a monitoring and treatment strategy in which doctors try to prevent high intracranial pressure (ICP), and also try to prevent low PbtO2 (brain tissue oxygen levels). This strategy is one of two alternative strategies that is currently used in standard care of patients with traumatic brain injury.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>ICP + PbtO2 guided management strategy</intervention_name>
    <description>In this management strategy, the physiological goal is to avoid ICP from exceeding 22 mm Hg and to avoid PbtO2 dropping below 20 mm Hg. ICP and PbtO2 are monitored using devices inserted into the brain through a hole in the skull. These devices are approved by the US Food and Drug Administration (FDA) and Health Canada for patients with severe TBI. The devices are used in standard care at hospitals participating in this research study. Doctors adjust their treatment choices to try to achieve these ICP and PbtO2 goals. Treatments include kinds and doses of medications and the amount of intravenous fluids given, ventilator (breathing machine) settings, need for blood transfusions, and other medical care. This management strategy is used to guide care for 5 days in this research study.</description>
    <arm_group_label>ICP + PbtO2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>ICP guided management strategy</intervention_name>
    <description>In this management strategy, the physiological goal is to avoid ICP from exceeding 22 mm Hg. ICP and PbtO2 are monitored using devices inserted into the brain through a hole in the skull, but PbtO2 is not used to guide care. These devices are approved by the US Food and Drug Administration (FDA) and Health Canada, and are routinely used in patients with severe TBI. Doctors adjust their treatment choices to try to achieve this ICP goal. Treatments include kinds and doses of medications and the amount of intravenous fluids given, ventilator (breathing machine) settings, need for blood transfusions, and other medical care. This management strategy is used to guide care for 5 days in this research study.</description>
    <arm_group_label>ICP only</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Non-penetrating traumatic brain injury&#xD;
&#xD;
          -  Glasgow Coma Scale (GCS) 3-8 measured off paralytics&#xD;
&#xD;
          -  Glasgow Coma Scale motor score &lt; 6 if endotracheally intubated&#xD;
&#xD;
          -  Evidence of intracranial trauma on CT scan&#xD;
&#xD;
          -  Able to place intracranial probes and randomize within 6 hours of arrival at enrolling&#xD;
             hospital&#xD;
&#xD;
          -  Able to place intracranial probes and randomize within 12 hours from injury&#xD;
&#xD;
          -  Age greater than or equal to 14 years&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Non-survivable injury&#xD;
&#xD;
          -  Bilaterally absent pupillary response in the absence of paralytic medication&#xD;
&#xD;
          -  Contraindication to the placement of intracranial probes&#xD;
&#xD;
          -  Treatment of brain tissue oxygen values prior to randomization&#xD;
&#xD;
          -  Planned use of devices which may unblind treating physicians to brain tissue hypoxia&#xD;
&#xD;
          -  Systemic sepsis at screening&#xD;
&#xD;
          -  Refractory hypotension&#xD;
&#xD;
          -  Refractory systemic hypoxia&#xD;
&#xD;
          -  PaO2/FiO2 ratio &lt; 200&#xD;
&#xD;
          -  Known pre-existing neurologic disease with confounding residual neurological deficits&#xD;
&#xD;
          -  Known inability to perform activities of daily living (ADL) without assistance prior&#xD;
             to injury&#xD;
&#xD;
          -  Known active drug or alcohol dependence that, in the opinion of site investigator,&#xD;
             would interfere with physiological response to brain tissue oxygen treatments&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Prisoner&#xD;
&#xD;
          -  On EFIC Opt-Out list as indicated by a bracelet or medical alert&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>14 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lori Shutter, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pittsburgh, Pittsburgh, PA 15260</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ramon Diaz-Arrastia, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pennsylvania, Philadelphia, PA 19104</affiliation>
  </overall_official>
  <overall_official>
    <last_name>William Barsan, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Michigan, Ann Arbor, MI 48109</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Sharon Yeatts, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical University of South Carolina, Charleston, SC 29425</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>William Barsan, MD</last_name>
    <phone>734-232-2141</phone>
    <email>wbarsan@umich.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>William J Meurer, MD</last_name>
    <phone>734-232-2141</phone>
    <email>wmeurer@umich.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Ronald Reagan UCLA Medical Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095-7436</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Paul Vespa, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Stanford University Medical Center</name>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Karen Hirsch</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>UC Davis Medical Center</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95817</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lara Zimmermann, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>San Francisco General Hospital</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Claude Hemphill</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>University of Colorado Hospital</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Robert Neumann</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Yale New Haven Hospital</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06510</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Emily Gilmore, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>UF Health Shands Hospital</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32608</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lisa Merck, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>University of Chicago Medical Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Christos Lazaridis, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Maine Medical Center</name>
      <address>
        <city>Portland</city>
        <state>Maine</state>
        <zip>04102</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Teresa May, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02128</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jeffrey Schweitzer, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Beth Israel Deaconess Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Martina Stippler, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>UMASS Memorial Medical Center</name>
      <address>
        <city>Worcester</city>
        <state>Massachusetts</state>
        <zip>01655</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Susanne Muehlschlegel</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Detroit Receiving Hospital</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Wazim Mohamed, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Henry Ford Hospital</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Christopher Lewandowski, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Regions Hospital</name>
      <address>
        <city>Saint Paul</city>
        <state>Minnesota</state>
        <zip>55101</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Michael Brogan</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Cooper University Hospital</name>
      <address>
        <city>Camden</city>
        <state>New Jersey</state>
        <zip>08103</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Alan Turtz, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>University of New Mexico Hospital</name>
      <address>
        <city>Albuquerque</city>
        <state>New Mexico</state>
        <zip>87131</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Huy Tran, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>North Shore University Hospital</name>
      <address>
        <city>Manhasset</city>
        <state>New York</state>
        <zip>11030</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>dAVID lEDOUX, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Strong Memorial Hospital</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14642</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Christopher Zammit</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>University of North Carolina Medical Center</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27514</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Rhonda Cadena, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Duke University Hospital</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Katharine Colton, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>University of Cincinnati Medical Center</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45219</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Natalie Kreitzer</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>OSU Wexner Medical Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Shraddha Mainali, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Riverside Methodist Hospital</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43214</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Chad Miller, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Oregon Health &amp; Science University Hospital</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>David Zonies, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Penn Presbyterian Medical Center</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Danielle Sandsmark</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Thomas Jefferson University Hospital</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19107</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jack Jallo, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>UPMC Presbyterian Hospital</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15212</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>David Okonkwo, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Memorial Hermann Hospital</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77024</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Ben Taub General Hospital</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Claudia Robertson, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>University of Utah Healthcare</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84132</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Holly Ledyard</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Harborview Medical Center</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98104</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Randall Chesnut</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>WVU Healthcare Ruby Memorial Hospital</name>
      <address>
        <city>Morgantown</city>
        <state>West Virginia</state>
        <zip>26506</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nathaniel Mohney, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Froedtert Hospital</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53226</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Vijay Johnson</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>CIUSSS-NIM Hopital du Sacre - Coeur de Montreal</name>
      <address>
        <city>Montréal</city>
        <zip>H4J 1C5</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Francis Bernard, MD</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://siren.network/clinical-trials/boost-3</url>
    <description>BOOST3 Study Website</description>
  </link>
  <reference>
    <citation>Okonkwo DO, Shutter LA, Moore C, Temkin NR, Puccio AM, Madden CJ, Andaluz N, Chesnut RM, Bullock MR, Grant GA, McGregor J, Weaver M, Jallo J, LeRoux PD, Moberg D, Barber J, Lazaridis C, Diaz-Arrastia RR. Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase-II: A Phase II Randomized Trial. Crit Care Med. 2017 Nov;45(11):1907-1914. doi: 10.1097/CCM.0000000000002619.</citation>
    <PMID>29028696</PMID>
  </reference>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>November 16, 2018</study_first_submitted>
  <study_first_submitted_qc>November 22, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 27, 2018</study_first_posted>
  <last_update_submitted>September 8, 2023</last_update_submitted>
  <last_update_submitted_qc>September 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Michigan</investigator_affiliation>
    <investigator_full_name>William Barsan</investigator_full_name>
    <investigator_title>Professor of Emergency Medicine</investigator_title>
  </responsible_party>
  <keyword>intracranial pressure</keyword>
  <keyword>hypoxia, brain</keyword>
  <keyword>critical care</keyword>
  <keyword>emergency treatment</keyword>
  <keyword>monitoring, physiologic</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brain Injuries</mesh_term>
    <mesh_term>Brain Injuries, Traumatic</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>The data will be stored in the NHLBI data repository after trial completion.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>1 year after publication on main outcome results paper</ipd_time_frame>
    <ipd_access_criteria>Data use agreement with the appropriate NHLBI repository</ipd_access_criteria>
  </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/NCT03754114
org study id: BOOST3
secondary id: U01NS099046
nct id: NCT03754114
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
BOOST3 is a randomized clinical trial to determine the comparative effectiveness of two
      strategies for monitoring and treating patients with traumatic brain injury (TBI) in the
      intensive care unit (ICU). The study will determine the safety and efficacy of a strategy
      guided by treatment goals based on both intracranial pressure (ICP) and brain tissue oxygen
      (PbtO2) as compared to a strategy guided by treatment goals based on ICP monitoring alone.
      Both of these alternative strategies are used in standard care. It is unknown if one is more
      effective than the other. In both strategies the monitoring and goals help doctors adjust
      treatments including the kinds and doses of medications and the amount of intravenous fluids
      given, ventilator (breathing machine) settings, need for blood transfusions, and other
      medical care. The results of this study will help doctors discover if one of these methods is
      more safe and effective.
BOOST3 is a randomized clinical trial to determine the comparative effectiveness of two
      strategies for monitoring and treating patients with traumatic brain injury (TBI) in the
      intensive care unit (ICU).

      When a person has a TBI, their injured brain can swell over a period of hours or days. If the
      brain swells too much, the pressure in the skull increases and becomes dangerous, causing
      further injury to the brain. To try to prevent this, doctors usually insert a device, an ICP
      monitor, into the brain through a hole in the skull of people with severe TBI. An ICP monitor
      measures the pressure inside the skull. Most doctors agree that it is important to measure
      and prevent high ICP. Patients with injured brains also suffer additional injury to the brain
      if the amount of oxygen in the brain gets too low. Some doctors also insert a second device,
      a PbtO2 monitor, in the brain through the same or a second hole in the skull to measure brain
      tissue oxygen. A PbtO2 monitor measures how much oxygen is in a small area of the brain near
      the tip of the monitor. Other doctors think this is unnecessary and unhelpful. Both
      monitoring devices are approved by the US Food and Drug Administration (FDA) and Health
      Canada for patients with TBI. Both are commonly used. The ICP and PbtO2 goals guided by these
      monitors are used to help doctors adjust their treatment choices. Treatments include kinds
      and doses of medications and the amount of intravenous fluids given, ventilator (breathing
      machine) settings, need for blood transfusions, and other medical care. Each of these
      treatment decisions is intended to improve outcomes. However, each treatment decision also
      involves potential risks. Different treatment decisions may result in different risks. This
      study will also help doctors better understand these risks. This study is funded by the
      National Institutes of Health because it answers questions important to the care of patients
      with TBI.

      This study is a two-arm, single-blind, randomized, controlled, phase III, multi-center trial
      of ICU monitoring and treatment strategies for patients with severe TBI. It will compare the
      efficacy of ICU care guided by PbtO2 and ICP monitoring versus monitoring of ICP alone in the
      first 5 days after injury. Only subjects who have severe TBI and require invasive monitoring,
      according to Brain Trauma Foundation (BTF) and American College of Surgeons-Trauma Quality
      Improvement (ACS TQIP) guidelines, will be enrolled. All participants in this study will have
      both ICP monitors and PbtO2 monitors. Half of the participants will be randomized to an arm
      that includes treatment informed by PbtO2 and ICP, and half will be randomized to an arm that
      treats only ICP.

      The PbtO2 values of those in the ICP only arm will be masked, so that the treating physicians
      will not be guided by PbtO2 information. Participants in the PbtO2 and ICP arm will have
      PbtO2 monitored and low measurements treated. Treatments to address physiological goals in
      both arms will follow a clinical standardization plan. Participants will be followed for 6
      months and occurrence of serious adverse events or death will be recorded. Participants will
      have a follow-up interview to assess their level of recovery approximately 6 months post
      injury.

      To reduce the likelihood of imbalance of important prognostic factors between groups, a
      covariate-adjusted randomization scheme will be used in this study. Adjustment variables are
      clinical site and probability of a poor outcome as defined by the IMPACT core model.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
masking description: The outcomes assessors will be blinded to the treatment assignment of the participant.
measure: Glasgow Outcome Scale-Extended (GOS-E)
time frame: 6 months
description: The Glasgow Outcome Scale-Extended (GOS-E) is a global scale for functional outcome, in which higher scores indicate better outcomes. The GOS-E rates patient status into one of eight categories. A GOS-E score of 1 indicates death, 2 indicates a vegetative state, 3 or 4 indicates severe disability, 5 or 6 indicates moderate disability, and 7 or 8 indicates good recovery. The categories of severe disability, moderate disability and good recovery are subdivided into a lower and upper category. All injury related disabilities are assessed.
measure: Survival
time frame: At discharge from hospital, an average of 19 days
description: Survival at discharge from hospital
measure: Total Brain Hypoxia Exposure
time frame: Inclusive of up to 5 days of study intervention
description: The cumulative area on the time versus brain tissue oxygenation (PbtO2) curve in which PbtO2 is less than 20 mmHg.
measure: Cognition: Rey Auditory Verbal Learning Test
time frame: 6 months
description: A measure of verbal learning and memory.
measure: Cognition: Trail Making Test Part A+B
time frame: 6 months
description: A measure of attention, visual-motor tracking and executive functioning.
measure: Emotional Health: Rivermead Post-Concussion Symptom Questionnaire
time frame: 6 months
description: A measure of the presence and severity of post-concussion somatic, cognitive, and emotional symptoms.
measure: Emotional Health: Brief Symptom Inventory 18
time frame: 6 months
description: A measure of psychological distress and psychiatric disorders.
measure: Emotional Health: Satisfaction with Life Scale
time frame: 6 months
description: A measure of global cognitive judgments of one's life satisfaction.
measure: Functional Status Exam
time frame: 6 months
description: Change in the activities of every day life as a function of a sudden event or illness
arm group label: ICP only
arm group type: Active Comparator
description: ICP guided management strategy: Care in the ICU of research participants randomized to this arm will be guided by a monitoring and treatment strategy in which doctors try to prevent high intracranial pressure (ICP) caused by a swollen brain. This strategy is one of two alternative strategies that is currently used in standard care of patients with traumatic brain injury.
arm group label: ICP + PbtO2
arm group type: Active Comparator
description: ICP + PbtO2 guided management strategy: Care in the ICU of research participants randomized to this arm will be guided by a monitoring and treatment strategy in which doctors try to prevent high intracranial pressure (ICP), and also try to prevent low PbtO2 (brain tissue oxygen levels). This strategy is one of two alternative strategies that is currently used in standard care of patients with traumatic brain injury.
intervention type: Other
intervention name: ICP + PbtO2 guided management strategy
description: In this management strategy, the physiological goal is to avoid ICP from exceeding 22 mm Hg and to avoid PbtO2 dropping below 20 mm Hg. ICP and PbtO2 are monitored using devices inserted into the brain through a hole in the skull. These devices are approved by the US Food and Drug Administration (FDA) and Health Canada for patients with severe TBI. The devices are used in standard care at hospitals participating in this research study. Doctors adjust their treatment choices to try to achieve these ICP and PbtO2 goals. Treatments include kinds and doses of medications and the amount of intravenous fluids given, ventilator (breathing machine) settings, need for blood transfusions, and other medical care. This management strategy is used to guide care for 5 days in this research study.
arm group label: ICP + PbtO2
intervention type: Other
intervention name: ICP guided management strategy
description: In this management strategy, the physiological goal is to avoid ICP from exceeding 22 mm Hg. ICP and PbtO2 are monitored using devices inserted into the brain through a hole in the skull, but PbtO2 is not used to guide care. These devices are approved by the US Food and Drug Administration (FDA) and Health Canada, and are routinely used in patients with severe TBI. Doctors adjust their treatment choices to try to achieve this ICP goal. Treatments include kinds and doses of medications and the amount of intravenous fluids given, ventilator (breathing machine) settings, need for blood transfusions, and other medical care. This management strategy is used to guide care for 5 days in this research study.
arm group label: ICP only
criteria: 
gender: All
minimum age: 14 Years
maximum age: N/A
healthy volunteers: No
last name: Lori Shutter, MD
role: Principal Investigator
affiliation: University of Pittsburgh, Pittsburgh, PA 15260
last name: Ramon Diaz-Arrastia, MD, PhD
role: Principal Investigator
affiliation: University of Pennsylvania, Philadelphia, PA 19104
last name: William Barsan, MD
role: Principal Investigator
affiliation: University of Michigan, Ann Arbor, MI 48109
last name: Sharon Yeatts, PhD
role: Principal Investigator
affiliation: Medical University of South Carolina, Charleston, SC 29425
last name: William Barsan, MD
phone: 734-232-2141
email: wbarsan@umich.edu
last name: William J Meurer, MD
phone: 734-232-2141
email: wmeurer@umich.edu
facility: 
status: Recruiting
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status: Active, not recruiting
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status: Recruiting
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country: Canada
country: United States
url: https://siren.network/clinical-trials/boost-3
description: BOOST3 Study Website
citation: Okonkwo DO, Shutter LA, Moore C, Temkin NR, Puccio AM, Madden CJ, Andaluz N, Chesnut RM, Bullock MR, Grant GA, McGregor J, Weaver M, Jallo J, LeRoux PD, Moberg D, Barber J, Lazaridis C, Diaz-Arrastia RR. Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase-II: A Phase II Randomized Trial. Crit Care Med. 2017 Nov;45(11):1907-1914. doi: 10.1097/CCM.0000000000002619.
PMID: 29028696
responsible party type: Principal Investigator
investigator affiliation: University of Michigan
investigator full name: William Barsan
investigator title: Professor of Emergency Medicine
mesh term: Brain Injuries
mesh term: Brain Injuries, Traumatic
sharing ipd: Yes
ipd description: The data will be stored in the NHLBI data repository after trial completion.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd time frame: 1 year after publication on main outcome results paper
ipd access criteria: Data use agreement with the appropriate NHLBI repository