xml: <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/NCT06036641</url>
    </required_header>
    <id_info>
      <org_study_id>IRAS [287464]</org_study_id>
      <secondary_id>CPMS ID - 56254</secondary_id>
      <nct_id>NCT06036641</nct_id>
    </id_info>
    <brief_title>The Effects of Prolonged Head-Down Tilt Lithotomy Position on Lower Limb Haemodynamics</brief_title>
    <acronym>HELP</acronym>
    <official_title>The Effects of Prolonged Head-Down Tilt Lithotomy Position on Lower Limb Haemodynamics in Adults Undergoing Minimally Invasive Abdominopelvic Surgery: An Intraoperative Observational Study</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of Portsmouth</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Portsmouth Hospitals NHS Trust</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>University of Portsmouth</source>
    <oversight_info>
      <has_dmc>No</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>
        During certain bowel surgeries for cancer (colorectal surgery), individuals frequently have&#xD;
        to be placed in a head-down position to enable surgeons have optimal access to the cancer&#xD;
        site. This position usually also involves bending the hips and knees while supporting the&#xD;
        legs in stirrups. However, lying in this position for long periods of time can lower the flow&#xD;
        of blood to the legs, which can potentially cause injury. A rare but severe consequence is&#xD;
        called Well-Leg Compartment Syndrome (WLCS). If WLCS is not diagnosed quickly, it can lead to&#xD;
        other difficult complications and a significant delay in recovery. Unfortunately, because the&#xD;
        individual is under anaesthesia, diagnosis is delayed in many cases. There is very little&#xD;
        information in the medical literature about how this damage to the legs progresses over the&#xD;
        course of the surgery. To better understand how WLSC, how well blood vessels work during&#xD;
        surgery will be assessed. The flow of blood and oxygen in the calf muscle will be assessed in&#xD;
        25 individuals placed in a head-down position during colorectal surgery. Likewise, blood&#xD;
        samples will be obtained in order to measure the biological markers that may contribute to&#xD;
        the development of WLCS.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The development of lower limb compartment syndrome in the absence of trauma (known as&#xD;
        well-leg compartment syndrome, WLCS) is a severe complication reported during prolonged&#xD;
        pelvic surgery. WLCS is characterised by muscular ischaemia and secondary necrosis from the&#xD;
        increase in hydrostatic pressure in a closed fascial compartment.&#xD;
  &#xD;
        The aetiology of WLCS appears to be primarily related to ischaemia of the lower limbs after a&#xD;
        prolonged period in the head-down tilt lithotomy (HDTL) position, which is commonly used to&#xD;
        access the pelvis and perineum during urological, colorectal, and gynaecological surgery.&#xD;
        Elevation of the lower limbs above the heart results in a ~2 mmHg drop in mean arterial&#xD;
        pressure at the mid-calf for every 2.5 cm that the limbs are raised. These hemodynamic&#xD;
        changes are accompanied by an increase in compartment pressures associated with limb&#xD;
        elevation and are further exacerbated by a steep (&gt;15°) head-down tilt. The outcome of these&#xD;
        changes ultimately leads to the development of significant and (often unrecognised)&#xD;
        intraoperative ischemia in the lower limbs.&#xD;
  &#xD;
        Prolonged reductions in lower limb perfusion during HDTL can cause the development of&#xD;
        localised tissue oedema, leading to marked intracompartmental hypertension, which is further&#xD;
        exacerbated once the limbs are lowered and reperfusion of ischemic muscle occurs. This is a&#xD;
        consequence known as ischaemic-reperfusion injury (IRI), a phenomenon where reperfusion per&#xD;
        se may result in a local and systemic inflammatory response that may augment tissue injury in&#xD;
        excess of that produced by ischaemia alone.&#xD;
  &#xD;
        Microvascular injury is considered one of the major determinants of IRI, particularly due to&#xD;
        increased permeability of capillaries and arterioles that lead to an increase in diffusion&#xD;
        and fluid filtration across the tissues. Subsequently, activated endothelial cells produce&#xD;
        more reactive oxygen species and less nitric oxide, and this imbalance results in a&#xD;
        corresponding inflammatory response and increased oxidative stress, which if sufficiently&#xD;
        severe lead to further lower limb muscle and nerve injury.&#xD;
  &#xD;
        The incidence of WLCS is unpredictable and as the individual is anaesthetised, the diagnosis&#xD;
        is delayed in many cases, so the residual motor-sensory deficit may be severe, even after&#xD;
        fasciotomy. Although there are many published case reports of this condition, it is likely&#xD;
        that many cases of WLCS go unreported, and some may be mild and escape clinical detection.&#xD;
        However, in cases that have been reported, the incidence of permanent disability after the&#xD;
        development of WLCS ranges from ≈30% to ≈100%.&#xD;
  &#xD;
        The paucity of detailed observational studies into the effects of HDTL on lower limb&#xD;
        haemodynamics and tissue oxygenation has restricted the ability of the clinical and&#xD;
        scientific society to construct clinical strategies to minimise this complication.&#xD;
        Identifying individuals with risk factors and increasing surveillance during surgery in these&#xD;
        people may allow for early detection and decrease the morbidity and potential mortality&#xD;
        associated with intraoperative WLCS.&#xD;
  &#xD;
        The study aims to assess lower limb haemodynamics by measuring cutaneous blood flow, muscle&#xD;
        and brain tissue oxygenation, inflammatory and oxidative stress biomarkers during pelvic&#xD;
        surgery in patients placed in HDTL. This study has the potential to provide a better&#xD;
        understanding of the pathogenesis of WLCS and add novel knowledge regarding its early&#xD;
        diagnosis.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 9, 2023</start_date>
    <completion_date type="Anticipated">October 9, 2024</completion_date>
    <primary_completion_date type="Anticipated">October 9, 2024</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Case-Only</observational_model>
      <time_perspective>Cross-Sectional</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Cutaneous blood flow</measure>
      <time_frame>baseline, during the surgery</time_frame>
      <description>Change over time in cutaneous blood flow in the legs relative to a vascular occlusion test (VOT) during surgery in the HDTL position.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Muscle tissue oxygenation</measure>
      <time_frame>baseline, during the surgery</time_frame>
      <description>Change over time in muscle tissue oxygenation in the lower limb relative to a vascular occlusion test (VOT) during surgery in the HDTL position.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma interleukin-6 (IL-6) concentration</measure>
      <time_frame>baseline, during the surgery</time_frame>
      <description>Change over time in [IL-6] during surgery in the HDTL position.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma Tumour Necrosis Factor Alpha (TNF-α) concentration</measure>
      <time_frame>baseline, during the surgery</time_frame>
      <description>Change over time in [TNF-α] during surgery in the HDTL position.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma Superoxide Dismutase (SOD) concentration</measure>
      <time_frame>baseline, during the surgery</time_frame>
      <description>Change over time in [SOD] during surgery in the HDTL position.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma Protein Carbonyl concentration</measure>
      <time_frame>baseline, during the surgery</time_frame>
      <description>Change over time in [protein carbonyl] during surgery in the HDTL position.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma nitrate concentration</measure>
      <time_frame>baseline, during the surgery</time_frame>
      <description>Change over time in [nitrate] during surgery in the HDTL position.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma nitrite concentration</measure>
      <time_frame>baseline, during the surgery</time_frame>
      <description>Change over time in [nitrite] during surgery in the HDTL position.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Mean arterial pressure (MAP)</measure>
      <time_frame>baseline, during the surgery</time_frame>
      <description>Change over time in MAP during surgery in the HDTL position.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Skin temperature</measure>
      <time_frame>baseline, during the surgery</time_frame>
      <description>Change over time in skin temperature during surgery in the HDTL position.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Brain tissue oxygenation</measure>
      <time_frame>continuous measurement during the surgery</time_frame>
      <description>Change over time in brain tissue oxygenation during surgery in the HDTL position.</description>
    </secondary_outcome>
    <number_of_groups>1</number_of_groups>
    <enrollment type="Anticipated">25</enrollment>
    <condition>Compartment Syndrome Nontraumatic Lower Extremity</condition>
    <arm_group>
      <arm_group_label>Colorectal surgery</arm_group_label>
      <description>Individuals scheduled for colorectal surgery in the HDTL position</description>
    </arm_group>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>NIRS monitoring</intervention_name>
      <description>All participants will undergo NIRS monitoring of muscle and cerebral tissue oxygenation intraoperatively.</description>
      <arm_group_label>Colorectal surgery</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>Laser Doppler flowmetry</intervention_name>
      <description>Cutaneous blood flow will be assessed intraoperatively via Laser Doppler flowmetry in all participants</description>
      <arm_group_label>Colorectal surgery</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Inflammatory and Oxidative stress biomarkers</intervention_name>
      <description>Blood samples will be taken to measure biomarkers of inflammation and oxidative stress at specific time points</description>
      <arm_group_label>Colorectal surgery</arm_group_label>
    </intervention>
    <eligibility>
      <study_pop>
        <textblock>
          Adult individuals(18 years and above) scheduled to undergo surgery in the HDTL position at&#xD;
          the Department of Colorectal Surgery, Queen Alexandra Hospital, Portsmouth Hospitals&#xD;
          University NHS Trust.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Adults scheduled to undergo colorectal surgery in the HDTL position&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  History of myocardial infarction or cerebro-vascular events in the last 12 months&#xD;
  &#xD;
            -  Previous revascularisation procedure in their lower limbs&#xD;
  &#xD;
            -  BMI &gt; 40 kg/m2&#xD;
  &#xD;
            -  Inability to give informed consent&#xD;
  &#xD;
            -  Other serious medical conditions, which in the opinion of study investigators, would&#xD;
               interfere with safety or data interpretation&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Chukwuemeka C Uzoma, MBBS</last_name>
      <role>Principal Investigator</role>
      <affiliation>University of Portsmouth</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Maria C Perissiou, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>University of Portsmouth</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Maria C Perissiou, PhD</last_name>
      <phone>+44 7762860432</phone>
      <email>maria.perissiou@port.ac.uk</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Chukwuemeka C Uzoma, MBBS</last_name>
      <phone>+44 7466733040</phone>
      <email>chukwuemeka.uzoma@port.ac.uk</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Queen Alexandra Hospital, Portsmouth Hospitals University NHS Trust</name>
        <address>
          <city>Portsmouth</city>
          <state>West Sussex</state>
          <zip>PO6 3LY</zip>
          <country>United Kingdom</country>
        </address>
      </facility>
      <contact>
        <last_name>Chukwuemeka C Uzoma, MBBS</last_name>
        <phone>07466733040</phone>
        <email>chukwuemeka.uzoma@port.ac.uk</email>
      </contact>
    </location>
    <location_countries>
      <country>United Kingdom</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>September 3, 2023</study_first_submitted>
    <study_first_submitted_qc>September 11, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 14, 2023</study_first_posted>
    <last_update_submitted>September 11, 2023</last_update_submitted>
    <last_update_submitted_qc>September 11, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 14, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>University of Portsmouth</investigator_affiliation>
      <investigator_full_name>Maria Perissiou</investigator_full_name>
      <investigator_title>Senior Lecturer</investigator_title>
    </responsible_party>
    <keyword>Head Down Tilt Lithotomy</keyword>
    <keyword>Minimally Invasive Surgery</keyword>
    <keyword>Ischaemia Reperfusion Syndrome</keyword>
    <keyword>Pathophysiology</keyword>
    <keyword>Near Infrared Spectroscopy, NIRS</keyword>
    <keyword>Robotic Assisted Laparoscopic Surgery</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Compartment Syndromes</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06036641
  org study id: IRAS [287464]
  secondary id: CPMS ID - 56254
  nct id: NCT06036641
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  During certain bowel surgeries for cancer (colorectal surgery), individuals frequently have
        to be placed in a head-down position to enable surgeons have optimal access to the cancer
        site. This position usually also involves bending the hips and knees while supporting the
        legs in stirrups. However, lying in this position for long periods of time can lower the flow
        of blood to the legs, which can potentially cause injury. A rare but severe consequence is
        called Well-Leg Compartment Syndrome (WLCS). If WLCS is not diagnosed quickly, it can lead to
        other difficult complications and a significant delay in recovery. Unfortunately, because the
        individual is under anaesthesia, diagnosis is delayed in many cases. There is very little
        information in the medical literature about how this damage to the legs progresses over the
        course of the surgery. To better understand how WLSC, how well blood vessels work during
        surgery will be assessed. The flow of blood and oxygen in the calf muscle will be assessed in
        25 individuals placed in a head-down position during colorectal surgery. Likewise, blood
        samples will be obtained in order to measure the biological markers that may contribute to
        the development of WLCS.
  The development of lower limb compartment syndrome in the absence of trauma (known as
        well-leg compartment syndrome, WLCS) is a severe complication reported during prolonged
        pelvic surgery. WLCS is characterised by muscular ischaemia and secondary necrosis from the
        increase in hydrostatic pressure in a closed fascial compartment.
  
        The aetiology of WLCS appears to be primarily related to ischaemia of the lower limbs after a
        prolonged period in the head-down tilt lithotomy (HDTL) position, which is commonly used to
        access the pelvis and perineum during urological, colorectal, and gynaecological surgery.
        Elevation of the lower limbs above the heart results in a ~2 mmHg drop in mean arterial
        pressure at the mid-calf for every 2.5 cm that the limbs are raised. These hemodynamic
        changes are accompanied by an increase in compartment pressures associated with limb
        elevation and are further exacerbated by a steep (>15°) head-down tilt. The outcome of these
        changes ultimately leads to the development of significant and (often unrecognised)
        intraoperative ischemia in the lower limbs.
  
        Prolonged reductions in lower limb perfusion during HDTL can cause the development of
        localised tissue oedema, leading to marked intracompartmental hypertension, which is further
        exacerbated once the limbs are lowered and reperfusion of ischemic muscle occurs. This is a
        consequence known as ischaemic-reperfusion injury (IRI), a phenomenon where reperfusion per
        se may result in a local and systemic inflammatory response that may augment tissue injury in
        excess of that produced by ischaemia alone.
  
        Microvascular injury is considered one of the major determinants of IRI, particularly due to
        increased permeability of capillaries and arterioles that lead to an increase in diffusion
        and fluid filtration across the tissues. Subsequently, activated endothelial cells produce
        more reactive oxygen species and less nitric oxide, and this imbalance results in a
        corresponding inflammatory response and increased oxidative stress, which if sufficiently
        severe lead to further lower limb muscle and nerve injury.
  
        The incidence of WLCS is unpredictable and as the individual is anaesthetised, the diagnosis
        is delayed in many cases, so the residual motor-sensory deficit may be severe, even after
        fasciotomy. Although there are many published case reports of this condition, it is likely
        that many cases of WLCS go unreported, and some may be mild and escape clinical detection.
        However, in cases that have been reported, the incidence of permanent disability after the
        development of WLCS ranges from ≈30% to ≈100%.
  
        The paucity of detailed observational studies into the effects of HDTL on lower limb
        haemodynamics and tissue oxygenation has restricted the ability of the clinical and
        scientific society to construct clinical strategies to minimise this complication.
        Identifying individuals with risk factors and increasing surveillance during surgery in these
        people may allow for early detection and decrease the morbidity and potential mortality
        associated with intraoperative WLCS.
  
        The study aims to assess lower limb haemodynamics by measuring cutaneous blood flow, muscle
        and brain tissue oxygenation, inflammatory and oxidative stress biomarkers during pelvic
        surgery in patients placed in HDTL. This study has the potential to provide a better
        understanding of the pathogenesis of WLCS and add novel knowledge regarding its early
        diagnosis.
  observational model: Case-Only
  time perspective: Cross-Sectional
  measure: Cutaneous blood flow
  time frame: baseline, during the surgery
  description: Change over time in cutaneous blood flow in the legs relative to a vascular occlusion test (VOT) during surgery in the HDTL position.
  measure: Muscle tissue oxygenation
  time frame: baseline, during the surgery
  description: Change over time in muscle tissue oxygenation in the lower limb relative to a vascular occlusion test (VOT) during surgery in the HDTL position.
  measure: Plasma interleukin-6 (IL-6) concentration
  time frame: baseline, during the surgery
  description: Change over time in [IL-6] during surgery in the HDTL position.
  measure: Plasma Tumour Necrosis Factor Alpha (TNF-α) concentration
  time frame: baseline, during the surgery
  description: Change over time in [TNF-α] during surgery in the HDTL position.
  measure: Plasma Superoxide Dismutase (SOD) concentration
  time frame: baseline, during the surgery
  description: Change over time in [SOD] during surgery in the HDTL position.
  measure: Plasma Protein Carbonyl concentration
  time frame: baseline, during the surgery
  description: Change over time in [protein carbonyl] during surgery in the HDTL position.
  measure: Plasma nitrate concentration
  time frame: baseline, during the surgery
  description: Change over time in [nitrate] during surgery in the HDTL position.
  measure: Plasma nitrite concentration
  time frame: baseline, during the surgery
  description: Change over time in [nitrite] during surgery in the HDTL position.
  measure: Mean arterial pressure (MAP)
  time frame: baseline, during the surgery
  description: Change over time in MAP during surgery in the HDTL position.
  measure: Skin temperature
  time frame: baseline, during the surgery
  description: Change over time in skin temperature during surgery in the HDTL position.
  measure: Brain tissue oxygenation
  time frame: continuous measurement during the surgery
  description: Change over time in brain tissue oxygenation during surgery in the HDTL position.
  arm group label: Colorectal surgery
  description: Individuals scheduled for colorectal surgery in the HDTL position
  intervention type: Device
  intervention name: NIRS monitoring
  description: All participants will undergo NIRS monitoring of muscle and cerebral tissue oxygenation intraoperatively.
  arm group label: Colorectal surgery
  intervention type: Device
  intervention name: Laser Doppler flowmetry
  description: Cutaneous blood flow will be assessed intraoperatively via Laser Doppler flowmetry in all participants
  arm group label: Colorectal surgery
  intervention type: Other
  intervention name: Inflammatory and Oxidative stress biomarkers
  description: Blood samples will be taken to measure biomarkers of inflammation and oxidative stress at specific time points
  arm group label: Colorectal surgery
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Chukwuemeka C Uzoma, MBBS
  role: Principal Investigator
  affiliation: University of Portsmouth
  last name: Maria C Perissiou, PhD
  role: Principal Investigator
  affiliation: University of Portsmouth
  last name: Maria C Perissiou, PhD
  phone: +44 7762860432
  email: maria.perissiou@port.ac.uk
  last name: Chukwuemeka C Uzoma, MBBS
  phone: +44 7466733040
  email: chukwuemeka.uzoma@port.ac.uk
  facility: 
  contact: 
  country: United Kingdom
  responsible party type: Principal Investigator
  investigator affiliation: University of Portsmouth
  investigator full name: Maria Perissiou
  investigator title: Senior Lecturer
  mesh term: Compartment Syndromes
  sharing ipd: No