<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/NCT02232165</url>
  </required_header>
  <id_info>
    <org_study_id>E-24927</org_study_id>
    <nct_id>NCT02232165</nct_id>
  </id_info>
  <brief_title>Mean Arterial Blood Pressure Treatment for Acute Spinal Cord Injury</brief_title>
  <acronym>MAPS</acronym>
  <official_title>Mean Arterial Pressure in Spinal Cord Injury (MAPS): Determination of Non-inferiority of a Mean Arterial Pressure Goal of 65 mmHg Compared to a Mean Arterial Pressure Goal of 85 mmHg in Acute Human Traumatic Spinal Cord Injury.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Calgary</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Hotchkiss Brain Institute, University of Calgary</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>AANS/CNS Section on Disorders of the Spine and Peripheral Nerves</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Calgary</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Current guidelines for the clinical management of acute spinal cord injury (SCI) recommend&#xD;
      maintenance of mean arterial blood pressure (MAP) at 85 to 90 mmHg for the first seven days&#xD;
      after SCI as a clinical option. Unfortunately, the medical evidence to support this&#xD;
      recommendation exists only at the clinical case series level (Class III data). Furthermore,&#xD;
      maintenance of sustained systemic hypertension, as per clinical guidelines, may be associated&#xD;
      with risks to the patient via adverse medical events. Given this equivocal evidence, the&#xD;
      investigators group has questioned the merit of sustained induced hypertension following&#xD;
      acute SCI and has previously conducted a randomized, prospective controlled feasibility study&#xD;
      to further examine this issue. This prior pilot study randomized patients with acute SCI to a&#xD;
      spinal cord perfusion pressure (SCPP = MAP - intrathecal pressure (ITP)) target of ≥ 75 mmHg&#xD;
      or to a control group (hypotension avoidance, MAP ≥ 65 mmHg). The primary endpoint measure&#xD;
      was defined as the change in American Spinal Injury Association (ASIA) motor score from&#xD;
      baseline. No difference in the primary outcome was noted at one-year post-SCI in this study.&#xD;
&#xD;
      In light of this pilot data, the investigators hypothesize that maintenance of normotension&#xD;
      (MAP ≥ 65mmHg) is not inferior to induced hypertension (MAP ≥ 85mmHg) for 7 days following&#xD;
      acute SCI. As such, the investigators propose to conduct a Phase III non-inferiority&#xD;
      prospective, randomized clinical trial in acute SCI patients. Subjects will be randomized&#xD;
      into one of two MAP management groups for 7 days; Group 1 will be managed with a target MAP ≥&#xD;
      65 mmHg, while Group 2 will be managed with a target MAP ≥ 85 mmHg. The primary endpoint will&#xD;
      be change in ASIA motor score from baseline at 12 months post injury. A difference of ≤10&#xD;
      ASIA motor points change from baseline between groups will be considered as non-inferiority.&#xD;
      Secondary endpoints will include ASIA sensory score, proportion of patients achieving a one&#xD;
      grade improvement in ASIA impairment scale, quality of life assessment (as measured by&#xD;
      Short-Form-36 [SF-36]) and functional outcome (as measured by the Spinal Cord Independence&#xD;
      Measure (SCIM) and Functional Independence Measure (FIM). These will be measured at baseline,&#xD;
      72 hours and 3, 6 and 12 months from injury. Adverse events will be meticulously recorded.&#xD;
      The information gleaned from this trial will provide valuable information for the acute&#xD;
      treatment of traumatic SCI and will serve the objective of optimizing current clinical&#xD;
      practice and thus maximizing medical and neurological outcome for individuals following acute&#xD;
      traumatic SCI.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <start_date>February 2013</start_date>
  <completion_date type="Actual">September 20, 2019</completion_date>
  <primary_completion_date type="Actual">September 20, 2019</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>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in ASIA motor score from baseline</measure>
    <time_frame>1 year post-injury</time_frame>
    <description>A difference of ≤10 ASIA motor points change from baseline between groups will be considered as non-inferiority.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>ASIA sensory score</measure>
    <time_frame>1 year post-injury</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients achieving a one-grade improvement in ASIA impairment scale (AIS)</measure>
    <time_frame>1 year post-injury</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life assessment with Short-Form-36 (SF-36)</measure>
    <time_frame>1 year post-injury</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional outcome assessment with FIM and SCIM</measure>
    <time_frame>1 year post-injury</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Number and severity of adverse events</measure>
    <time_frame>Within 1 year of study enrolment</time_frame>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">17</enrollment>
  <condition>Acute Spinal Cord Injury</condition>
  <arm_group>
    <arm_group_label>Hypotension avoidance (MAP &gt;= 65 mmHg)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Mean arterial blood pressure is maintained &gt;= 65 mmHg for 7 days following acute SCI.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Induced hypertension (MAP &gt;= 85 mmHg)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Induced hypertension with mean arterial blood pressure &gt;= 85 mmHg for 7 days following acute SCI.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Hypotension avoidance</intervention_name>
    <description>Induced hypertension with MAP &gt;= 85 mmHg for 7 days following SCI is the current recommended clinical option guideline. Our intervention tests whether hypotension avoidance and maintenance of MAP &gt;= 65 mmHg is not inferior to induced hypertension.</description>
    <arm_group_label>Hypotension avoidance (MAP &gt;= 65 mmHg)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Induced hypertension</intervention_name>
    <description>Induced hypertension with MAP &gt;= 85 mmHg for 7 days following SCI is the current recommended clinical option guideline.</description>
    <arm_group_label>Induced hypertension (MAP &gt;= 85 mmHg)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age greater than or equal to 16 years.&#xD;
&#xD;
          -  Motor complete or incomplete (ASIA A, B, or C) acute traumatic SCI involving spinal&#xD;
             levels between C0 and T12.&#xD;
&#xD;
          -  Written and informed consent from patient or a legally acceptable representative.&#xD;
&#xD;
          -  Randomization and initiation of management protocol within 24 hours of injury.&#xD;
&#xD;
          -  Reasonable expectation of availability to receive the full 7-day course of therapy and&#xD;
             be available for follow up evaluations.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Acute traumatic SCI &gt; 24 hours old.&#xD;
&#xD;
          -  Central cord syndrome, defined as ASIA C or D with mean lower extremity score greater&#xD;
             than upper extremity score.&#xD;
&#xD;
          -  Isolated sensory deficit, motor intact.&#xD;
&#xD;
          -  Isolated radicular motor deficit, defined as a unilateral motor deficit restricted to&#xD;
             a single myotome.&#xD;
&#xD;
          -  Pregnancy.&#xD;
&#xD;
          -  Associated conditions interfering with informed consent or outcome assessment&#xD;
             including closed head injury and major orthopedic injuries.&#xD;
&#xD;
          -  Polytrauma: Abbreviated Injury Severity Score &gt;3 in any area other than head.&#xD;
&#xD;
          -  Known uncorrected severe coronary artery disease or evidence of active coronary&#xD;
             ischemia (ECG changes, positive troponin) will be excluded.&#xD;
&#xD;
          -  Advanced cardiac, pulmonary, hepatic or liver disease; the former will be&#xD;
             operationally defined using NCI Toxicity Criteria (Grade 2 or higher).&#xD;
&#xD;
          -  Allergy or other contraindication to norepinephrine.&#xD;
&#xD;
          -  A known diagnosis of cancer (except basal cell cancer).&#xD;
&#xD;
          -  Uncontrolled hypertension, defined as blood pressure persistently above 220 mmHg&#xD;
             systolic or 120 mmHg diastolic, despite antihypertensive therapy.&#xD;
&#xD;
          -  Any patients living in a nursing home or supervised living centre. Patients must be&#xD;
             historically fully independent in all activities of daily living including banking,&#xD;
             shopping, cooking, toileting, showering and dressing.&#xD;
&#xD;
          -  Any other medical condition, in the investigator's opinion, for which the patient&#xD;
             should not be included in the trial.&#xD;
&#xD;
          -  Pre-existing and active major psychiatric or other chronic neurological disease.&#xD;
&#xD;
          -  Patients who have a history of substance abuse or dependency within 12 months prior to&#xD;
             the study.&#xD;
&#xD;
          -  Currently participating in another interventional investigational study.&#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>W. Bradley Jacobs, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Calgary</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Texas Health Science Center San Antonio</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Calgary, Foothills Medical Centre</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <zip>T2N2T9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2019</verification_date>
  <study_first_submitted>September 2, 2014</study_first_submitted>
  <study_first_submitted_qc>September 4, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 5, 2014</study_first_posted>
  <last_update_submitted>September 24, 2019</last_update_submitted>
  <last_update_submitted_qc>September 24, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">September 25, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Calgary</investigator_affiliation>
    <investigator_full_name>Dr W. Bradley Jacobs</investigator_full_name>
    <investigator_title>Assistant Professor, Department of Clinical Neurosciences</investigator_title>
  </responsible_party>
  <keyword>acute spinal cord injury</keyword>
  <keyword>hemodynamic therapy</keyword>
  <keyword>functional outcome</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Spinal Cord Injuries</mesh_term>
    <mesh_term>Wounds and Injuries</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/NCT02232165
org study id: E-24927
nct id: NCT02232165
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
Current guidelines for the clinical management of acute spinal cord injury (SCI) recommend
      maintenance of mean arterial blood pressure (MAP) at 85 to 90 mmHg for the first seven days
      after SCI as a clinical option. Unfortunately, the medical evidence to support this
      recommendation exists only at the clinical case series level (Class III data). Furthermore,
      maintenance of sustained systemic hypertension, as per clinical guidelines, may be associated
      with risks to the patient via adverse medical events. Given this equivocal evidence, the
      investigators group has questioned the merit of sustained induced hypertension following
      acute SCI and has previously conducted a randomized, prospective controlled feasibility study
      to further examine this issue. This prior pilot study randomized patients with acute SCI to a
      spinal cord perfusion pressure (SCPP = MAP - intrathecal pressure (ITP)) target of ≥ 75 mmHg
      or to a control group (hypotension avoidance, MAP ≥ 65 mmHg). The primary endpoint measure
      was defined as the change in American Spinal Injury Association (ASIA) motor score from
      baseline. No difference in the primary outcome was noted at one-year post-SCI in this study.

      In light of this pilot data, the investigators hypothesize that maintenance of normotension
      (MAP ≥ 65mmHg) is not inferior to induced hypertension (MAP ≥ 85mmHg) for 7 days following
      acute SCI. As such, the investigators propose to conduct a Phase III non-inferiority
      prospective, randomized clinical trial in acute SCI patients. Subjects will be randomized
      into one of two MAP management groups for 7 days; Group 1 will be managed with a target MAP ≥
      65 mmHg, while Group 2 will be managed with a target MAP ≥ 85 mmHg. The primary endpoint will
      be change in ASIA motor score from baseline at 12 months post injury. A difference of ≤10
      ASIA motor points change from baseline between groups will be considered as non-inferiority.
      Secondary endpoints will include ASIA sensory score, proportion of patients achieving a one
      grade improvement in ASIA impairment scale, quality of life assessment (as measured by
      Short-Form-36 [SF-36]) and functional outcome (as measured by the Spinal Cord Independence
      Measure (SCIM) and Functional Independence Measure (FIM). These will be measured at baseline,
      72 hours and 3, 6 and 12 months from injury. Adverse events will be meticulously recorded.
      The information gleaned from this trial will provide valuable information for the acute
      treatment of traumatic SCI and will serve the objective of optimizing current clinical
      practice and thus maximizing medical and neurological outcome for individuals following acute
      traumatic SCI.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: Change in ASIA motor score from baseline
time frame: 1 year post-injury
description: A difference of ≤10 ASIA motor points change from baseline between groups will be considered as non-inferiority.
measure: ASIA sensory score
time frame: 1 year post-injury
measure: Proportion of patients achieving a one-grade improvement in ASIA impairment scale (AIS)
time frame: 1 year post-injury
measure: Quality of life assessment with Short-Form-36 (SF-36)
time frame: 1 year post-injury
measure: Functional outcome assessment with FIM and SCIM
time frame: 1 year post-injury
measure: Number and severity of adverse events
time frame: Within 1 year of study enrolment
arm group label: Hypotension avoidance (MAP >= 65 mmHg)
arm group type: Experimental
description: Mean arterial blood pressure is maintained >= 65 mmHg for 7 days following acute SCI.
arm group label: Induced hypertension (MAP >= 85 mmHg)
arm group type: Active Comparator
description: Induced hypertension with mean arterial blood pressure >= 85 mmHg for 7 days following acute SCI.
intervention type: Other
intervention name: Hypotension avoidance
description: Induced hypertension with MAP >= 85 mmHg for 7 days following SCI is the current recommended clinical option guideline. Our intervention tests whether hypotension avoidance and maintenance of MAP >= 65 mmHg is not inferior to induced hypertension.
arm group label: Hypotension avoidance (MAP >= 65 mmHg)
intervention type: Other
intervention name: Induced hypertension
description: Induced hypertension with MAP >= 85 mmHg for 7 days following SCI is the current recommended clinical option guideline.
arm group label: Induced hypertension (MAP >= 85 mmHg)
criteria: 
gender: All
minimum age: 16 Years
maximum age: N/A
healthy volunteers: No
last name: W. Bradley Jacobs, MD
role: Principal Investigator
affiliation: University of Calgary
facility: 
facility: 
country: Canada
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Calgary
investigator full name: Dr W. Bradley Jacobs
investigator title: Assistant Professor, Department of Clinical Neurosciences
mesh term: Spinal Cord Injuries
mesh term: Wounds and Injuries