<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/NCT03791996</url>
  </required_header>
  <id_info>
    <org_study_id>CCO-RCT</org_study_id>
    <nct_id>NCT03791996</nct_id>
  </id_info>
  <brief_title>Cranioplasty Cognitive Outcome Study</brief_title>
  <official_title>Impact of Cranioplasty on Cognitive Outcome: A Multi-Center Prospective Randomized Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kwong Wah Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The Queen Elizabeth Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Queen Mary Hospital, Hong Kong</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Prince of Wales Hospital, Shatin, Hong Kong</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Princess Margaret Hospital, Canada</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Tuen Mun Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Pamela Youde Nethersole Eastern Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Kwong Wah Hospital</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>
      This will be a multicenter prospective randomized study of adult patients with an acquired&#xD;
      skull defect as a result of craniectomy and considered suitable for cranioplasty, i.e.&#xD;
      reconstruction of the skull defect, at all seven Hong Kong Hospital Authority neurosurgical&#xD;
      units. Patients that underwent their primary craniectomy operation at any of the Hospital&#xD;
      Authority neurosurgery centers from the 1st March 2019 and considered suitable for&#xD;
      cranioplasty will be included in this study. Those who underwent their primary craniectomy&#xD;
      before 1st March 2019 or at an institution other than the aforementioned neurosurgical units&#xD;
      will be excluded. Data from clinical records, operation notes, medication-dispensing records,&#xD;
      laboratory records and radiological reports will be collected.&#xD;
&#xD;
      30 adult patients with craniectomy will be recruited and randomized into two groups: &quot;early&quot;&#xD;
      cranioplasty, i.e. performed within 3 months of craniectomy, and &quot;late&quot;, i.e. cranioplasty&#xD;
      performed more than 3 months after the operation. The aim of the study is to determine&#xD;
      whether early cranioplasty can improve on patient's cognitive performance compared to those&#xD;
      who undergo the procedure after 3 months.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Decompressive craniectomy, a neurosurgical procedure where a portion of the skull calvarium&#xD;
      is removed, is a life-saving procedure. The complication rate of cranioplasty, a&#xD;
      neurosurgical procedure where the acquired skull defect is reconstructed, ranges from 11% to&#xD;
      26% and includes postoperative hemorrhage and infection. (4) The syndrome of the trephined is&#xD;
      a recognized long-term complication in which certain groups of patients, experience&#xD;
      debilitating neurocognitive deficits in addition to chronic headache, dizziness, fatigability&#xD;
      and clinical depression. (2) It is believed that the lack of an overlying bone may cause&#xD;
      undue significant atmospheric pressure on the underlying cortex, thereby reducing cerebral&#xD;
      perfusion and cerebrospinal fluid flow. There are reports that cognitive improvement can be&#xD;
      observed in up to 30% of patients after cranioplasty yet the underlying mechanism for this&#xD;
      observation is unclear. (1) Some studies have demonstrated enhanced cerebral perfusion by&#xD;
      non-invasive investigations, but there is a lack of large scale systematically performed&#xD;
      studies to verify such cerebral hemodynamic effects. (1-3) Clinical equipoise exists&#xD;
      regarding the optimum timing of cranioplasty procedures after craniectomies. While the&#xD;
      anecdotal practice of delaying cranioplasty for at least 3 months after a craniectomy is&#xD;
      common, local and overseas observational studies suggest that performing early cranioplasties&#xD;
      (i.e. within 3 months) is equally safe in terms of infection and other operative&#xD;
      complications. (4-6)&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">March 1, 2019</start_date>
  <completion_date type="Anticipated">March 1, 2021</completion_date>
  <primary_completion_date type="Anticipated">September 1, 2020</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>
    <intervention_model_description>2-arm randomised study with subjects centrally randomised by assigning them into either the control &quot;late&quot; cranioplasty group or the intervention &quot;early&quot; cranioplasty group.&#xD;
All subjects will eventually receive the cranioplasty procedure.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>1:1 block central randomisation with assignments written on a card sealed in an opaque envelop.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Montreal Cognitive Assessment (MOCA)</measure>
    <time_frame>3-months</time_frame>
    <description>Minimum (worse): 0/30; Maximum (best) 30/30. Higher values represent a better outcome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Neurobehavioural Cognitive State Examination (NCSE)</measure>
    <time_frame>3-months</time_frame>
    <description>Multi-domain assessment involving: orientation, attention, registration, comprehension, repetition, naming, construction, calculation, similarities,judgement. Stratification of each domain into mild, moderate and severe impairment. The higher the number the better the outcome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Rivermead Behavioural Memory Test (RBMT)</measure>
    <time_frame>3-months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Motor assessment</measure>
    <time_frame>3-months</time_frame>
    <description>Medical Research Council limb power</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Modified Functional Ambulation Category (MFAC)</measure>
    <time_frame>3-months</time_frame>
    <description>7 ordinal scale assessment. The lower the scale, the worse the ambulatory ability of the patient. I: bed bound; 2: wheel-chair bound; 3: dependent walker; 4: Assisted walker; 5: Supervised walker; 6: Indoor walker; 7: Outdoor walker (patient can walk anywhere).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life assessment</measure>
    <time_frame>3-months</time_frame>
    <description>Short Form-36 (SF-36)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Psychological assessment</measure>
    <time_frame>3-months</time_frame>
    <description>Beck depression inventory (BDI)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Caregiver assessment</measure>
    <time_frame>3-months</time_frame>
    <description>Caregiver Strain Index</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Caregiver</measure>
    <time_frame>3-months</time_frame>
    <description>Caregiver self-assessment questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MRI cerebral perfusion assessment</measure>
    <time_frame>3-months</time_frame>
    <description>Cerebral blood flow</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Cognitive Impairment</condition>
  <condition>Brain Herniation</condition>
  <arm_group>
    <arm_group_label>&quot;Late&quot; cranioplasty</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Subjects undergoing cranioplasty within 3 months after craniectomy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>&quot;Early&quot; cranioplasty</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects undergoing cranioplasty beyond 3 months after craniectomy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>&quot;Early&quot; cranioplasty</intervention_name>
    <description>Subjects undergoing cranioplasty beyond 3 months after craniectomy.</description>
    <arm_group_label>&quot;Early&quot; cranioplasty</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age greater than or equal to 18 years-old,&#xD;
&#xD;
          2. Craniectomy was performed due to head injury, infarct or spontaneous intracerebral&#xD;
             hemorrhage, and benign tumors.&#xD;
&#xD;
          3. Craniectomy skull defect size of &gt;10cm at its longest diameter&#xD;
&#xD;
          4. Craniectomy performed at any of the Hospital Authority's Neurosurgical Centers after&#xD;
             1st March 2019&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Age older than 80 years-old,&#xD;
&#xD;
          2. Patients cannot communicate by obeying simple command,&#xD;
&#xD;
          3. Patients who are unfit for cranioplasty as decided by the treating neurosurgeon&#xD;
&#xD;
          4. Posterior fossa craniectomy&#xD;
&#xD;
          5. Craniectomy performed before 1st March 2019&#xD;
&#xD;
          6. Craniectomy performed at an institution outside the Hospital Authority&#xD;
&#xD;
          7. Any pre-existing illness that renders the patient moderately or severely disabled&#xD;
             before the brain insult.&#xD;
&#xD;
          8. Patients that need an additional procedure e.g. cerebrospinal fluid shunting with&#xD;
             cranioplasty in the same setting.&#xD;
&#xD;
          9. History of central nervous system infection&#xD;
&#xD;
         10. Craniectomy-related complications such as hemorrhage or surgical site infection&#xD;
             requiring surgical intervention or deemed to affect patient's long-term cognitive&#xD;
             outcome&#xD;
&#xD;
         11. Claustrophobia or any other medical condition that prohibits the patient from undergo&#xD;
             MRI scanning&#xD;
&#xD;
         12. Patients who cannot understand spoken English or Chinese&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>79 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Calvin Mak, MBBS FRCS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Neurosurgery, Queen Elizabeth Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Calvin Mak, MBBS FRCS</last_name>
    <phone>35066026</phone>
    <email>mhk349@ha.org.hk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Marina Lee</last_name>
    <phone>35066026</phone>
    <email>leeymm@ha.org.hk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Kwong Wah Hospital</name>
      <address>
        <city>Hong Kong</city>
        <state>Hong Kong</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Peter YM Woo, FRCS (SN)</last_name>
      <phone>852+ 3517 2275</phone>
      <phone_ext>2275</phone_ext>
      <email>peterymwoo@gmail.com</email>
    </contact>
    <investigator>
      <last_name>Peter YM Woo, FRCS (SN)</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Halani SH, Chu JK, Malcolm JG, Rindler RS, Allen JW, Grossberg JA, Pradilla G, Ahmad FU. Effects of Cranioplasty on Cerebral Blood Flow Following Decompressive Craniectomy: A Systematic Review of the Literature. Neurosurgery. 2017 Aug 1;81(2):204-216. doi: 10.1093/neuros/nyx054.</citation>
    <PMID>28368505</PMID>
  </reference>
  <results_reference>
    <citation>Bender A, Heulin S, Rohrer S, Mehrkens JH, Heidecke V, Straube A, Pfefferkorn T. Early cranioplasty may improve outcome in neurological patients with decompressive craniectomy. Brain Inj. 2013;27(9):1073-9. doi: 10.3109/02699052.2013.794972. Epub 2013 May 10.</citation>
    <PMID>23662672</PMID>
  </results_reference>
  <results_reference>
    <citation>Ashayeri K, M Jackson E, Huang J, Brem H, Gordon CR. Syndrome of the Trephined: A Systematic Review. Neurosurgery. 2016 Oct;79(4):525-34. doi: 10.1227/NEU.0000000000001366.</citation>
    <PMID>27489166</PMID>
  </results_reference>
  <results_reference>
    <citation>Malcolm JG, Rindler RS, Chu JK, Grossberg JA, Pradilla G, Ahmad FU. Complications following cranioplasty and relationship to timing: A systematic review and meta-analysis. J Clin Neurosci. 2016 Nov;33:39-51. doi: 10.1016/j.jocn.2016.04.017. Epub 2016 Aug 4.</citation>
    <PMID>27499122</PMID>
  </results_reference>
  <results_reference>
    <citation>Xu H, Niu C, Fu X, Ding W, Ling S, Jiang X, Ji Y. Early cranioplasty vs. late cranioplasty for the treatment of cranial defect: A systematic review. Clin Neurol Neurosurg. 2015 Sep;136:33-40. doi: 10.1016/j.clineuro.2015.05.031. Epub 2015 May 29.</citation>
    <PMID>26056810</PMID>
  </results_reference>
  <results_reference>
    <citation>Tsang AC, Hui VK, Lui WM, Leung GK. Complications of post-craniectomy cranioplasty: risk factor analysis and implications for treatment planning. J Clin Neurosci. 2015 May;22(5):834-7. doi: 10.1016/j.jocn.2014.11.021. Epub 2015 Mar 28.</citation>
    <PMID>25827865</PMID>
  </results_reference>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>December 30, 2018</study_first_submitted>
  <study_first_submitted_qc>December 30, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">January 3, 2019</study_first_posted>
  <last_update_submitted>October 15, 2019</last_update_submitted>
  <last_update_submitted_qc>October 15, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 17, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Kwong Wah Hospital</investigator_affiliation>
    <investigator_full_name>Peter Woo Yat Ming</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Cranioplasty</keyword>
  <keyword>Craniectomy</keyword>
  <keyword>Cognitive impairment</keyword>
  <keyword>Syndrome of the trephined</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cognitive Dysfunction</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03791996
org study id: CCO-RCT
nct id: NCT03791996
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This will be a multicenter prospective randomized study of adult patients with an acquired
      skull defect as a result of craniectomy and considered suitable for cranioplasty, i.e.
      reconstruction of the skull defect, at all seven Hong Kong Hospital Authority neurosurgical
      units. Patients that underwent their primary craniectomy operation at any of the Hospital
      Authority neurosurgery centers from the 1st March 2019 and considered suitable for
      cranioplasty will be included in this study. Those who underwent their primary craniectomy
      before 1st March 2019 or at an institution other than the aforementioned neurosurgical units
      will be excluded. Data from clinical records, operation notes, medication-dispensing records,
      laboratory records and radiological reports will be collected.

      30 adult patients with craniectomy will be recruited and randomized into two groups: "early"
      cranioplasty, i.e. performed within 3 months of craniectomy, and "late", i.e. cranioplasty
      performed more than 3 months after the operation. The aim of the study is to determine
      whether early cranioplasty can improve on patient's cognitive performance compared to those
      who undergo the procedure after 3 months.
Decompressive craniectomy, a neurosurgical procedure where a portion of the skull calvarium
      is removed, is a life-saving procedure. The complication rate of cranioplasty, a
      neurosurgical procedure where the acquired skull defect is reconstructed, ranges from 11% to
      26% and includes postoperative hemorrhage and infection. (4) The syndrome of the trephined is
      a recognized long-term complication in which certain groups of patients, experience
      debilitating neurocognitive deficits in addition to chronic headache, dizziness, fatigability
      and clinical depression. (2) It is believed that the lack of an overlying bone may cause
      undue significant atmospheric pressure on the underlying cortex, thereby reducing cerebral
      perfusion and cerebrospinal fluid flow. There are reports that cognitive improvement can be
      observed in up to 30% of patients after cranioplasty yet the underlying mechanism for this
      observation is unclear. (1) Some studies have demonstrated enhanced cerebral perfusion by
      non-invasive investigations, but there is a lack of large scale systematically performed
      studies to verify such cerebral hemodynamic effects. (1-3) Clinical equipoise exists
      regarding the optimum timing of cranioplasty procedures after craniectomies. While the
      anecdotal practice of delaying cranioplasty for at least 3 months after a craniectomy is
      common, local and overseas observational studies suggest that performing early cranioplasties
      (i.e. within 3 months) is equally safe in terms of infection and other operative
      complications. (4-6)
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: 2-arm randomised study with subjects centrally randomised by assigning them into either the control "late" cranioplasty group or the intervention "early" cranioplasty group.
All subjects will eventually receive the cranioplasty procedure.
primary purpose: Treatment
masking: None (Open Label)
masking description: 1:1 block central randomisation with assignments written on a card sealed in an opaque envelop.
measure: Montreal Cognitive Assessment (MOCA)
time frame: 3-months
description: Minimum (worse): 0/30; Maximum (best) 30/30. Higher values represent a better outcome.
measure: Neurobehavioural Cognitive State Examination (NCSE)
time frame: 3-months
description: Multi-domain assessment involving: orientation, attention, registration, comprehension, repetition, naming, construction, calculation, similarities,judgement. Stratification of each domain into mild, moderate and severe impairment. The higher the number the better the outcome.
measure: Rivermead Behavioural Memory Test (RBMT)
time frame: 3-months
measure: Motor assessment
time frame: 3-months
description: Medical Research Council limb power
measure: Modified Functional Ambulation Category (MFAC)
time frame: 3-months
description: 7 ordinal scale assessment. The lower the scale, the worse the ambulatory ability of the patient. I: bed bound; 2: wheel-chair bound; 3: dependent walker; 4: Assisted walker; 5: Supervised walker; 6: Indoor walker; 7: Outdoor walker (patient can walk anywhere).
measure: Quality of life assessment
time frame: 3-months
description: Short Form-36 (SF-36)
measure: Psychological assessment
time frame: 3-months
description: Beck depression inventory (BDI)
measure: Caregiver assessment
time frame: 3-months
description: Caregiver Strain Index
measure: Caregiver
time frame: 3-months
description: Caregiver self-assessment questionnaire
measure: MRI cerebral perfusion assessment
time frame: 3-months
description: Cerebral blood flow
arm group label: "Late" cranioplasty
arm group type: No Intervention
description: Subjects undergoing cranioplasty within 3 months after craniectomy.
arm group label: "Early" cranioplasty
arm group type: Experimental
description: Subjects undergoing cranioplasty beyond 3 months after craniectomy.
intervention type: Procedure
intervention name: "Early" cranioplasty
description: Subjects undergoing cranioplasty beyond 3 months after craniectomy.
arm group label: "Early" cranioplasty
criteria: 
gender: All
minimum age: 18 Years
maximum age: 79 Years
healthy volunteers: No
last name: Calvin Mak, MBBS FRCS
role: Principal Investigator
affiliation: Neurosurgery, Queen Elizabeth Hospital
last name: Calvin Mak, MBBS FRCS
phone: 35066026
email: mhk349@ha.org.hk
last name: Marina Lee
phone: 35066026
email: leeymm@ha.org.hk
facility: 
status: Recruiting
contact: 
investigator: 
country: China
citation: Halani SH, Chu JK, Malcolm JG, Rindler RS, Allen JW, Grossberg JA, Pradilla G, Ahmad FU. Effects of Cranioplasty on Cerebral Blood Flow Following Decompressive Craniectomy: A Systematic Review of the Literature. Neurosurgery. 2017 Aug 1;81(2):204-216. doi: 10.1093/neuros/nyx054.
PMID: 28368505
citation: Bender A, Heulin S, Rohrer S, Mehrkens JH, Heidecke V, Straube A, Pfefferkorn T. Early cranioplasty may improve outcome in neurological patients with decompressive craniectomy. Brain Inj. 2013;27(9):1073-9. doi: 10.3109/02699052.2013.794972. Epub 2013 May 10.
PMID: 23662672
citation: Ashayeri K, M Jackson E, Huang J, Brem H, Gordon CR. Syndrome of the Trephined: A Systematic Review. Neurosurgery. 2016 Oct;79(4):525-34. doi: 10.1227/NEU.0000000000001366.
PMID: 27489166
citation: Malcolm JG, Rindler RS, Chu JK, Grossberg JA, Pradilla G, Ahmad FU. Complications following cranioplasty and relationship to timing: A systematic review and meta-analysis. J Clin Neurosci. 2016 Nov;33:39-51. doi: 10.1016/j.jocn.2016.04.017. Epub 2016 Aug 4.
PMID: 27499122
citation: Xu H, Niu C, Fu X, Ding W, Ling S, Jiang X, Ji Y. Early cranioplasty vs. late cranioplasty for the treatment of cranial defect: A systematic review. Clin Neurol Neurosurg. 2015 Sep;136:33-40. doi: 10.1016/j.clineuro.2015.05.031. Epub 2015 May 29.
PMID: 26056810
citation: Tsang AC, Hui VK, Lui WM, Leung GK. Complications of post-craniectomy cranioplasty: risk factor analysis and implications for treatment planning. J Clin Neurosci. 2015 May;22(5):834-7. doi: 10.1016/j.jocn.2014.11.021. Epub 2015 Mar 28.
PMID: 25827865
responsible party type: Principal Investigator
investigator affiliation: Kwong Wah Hospital
investigator full name: Peter Woo Yat Ming
investigator title: Principal Investigator
mesh term: Cognitive Dysfunction
sharing ipd: No