<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/NCT04449614</url>
  </required_header>
  <id_info>
    <org_study_id>IRAS 238420</org_study_id>
    <nct_id>NCT04449614</nct_id>
  </id_info>
  <brief_title>A Review of Surgical Management of Congenital Pulmonary Airway Malformations (CPAM): A Decade of Experience</brief_title>
  <acronym>CPAM</acronym>
  <official_title>A Review of Surgical Management of Congenital Pulmonary Airway Malformations (CPAM): A Decade of Experience</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>King's College Hospital NHS Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>King's College London</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>King's College Hospital NHS Trust</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>
      Congenital pulmonary malformation in children is a rare abnormality mostly diagnosed before&#xD;
      birth during antenatal ultrasound examinations. These lesions may expand to form lung cysts&#xD;
      in children, cause recurrent lung infections and has a potential for malignant change.&#xD;
      Therefore, surgical removal in childhood is favoured as the treatment of choice.&#xD;
&#xD;
      The surgical correction may involve 'open' surgery or 'key hole' surgery. There is, however,&#xD;
      a variation in surgical and anaesthetic techniques and timing of this surgery and subsequent&#xD;
      complications reported post-surgery.&#xD;
&#xD;
      The purpose of this investigation is to review anaesthetic and surgical case notes and the&#xD;
      subsequent well-being of all children who underwent lung surgery to remove above lung lesions&#xD;
      over the last 10 years (2008-2017) at a regional centre. The aim is to look at the current&#xD;
      status of these children in relation to their health, growth and development evaluated via a&#xD;
      20-minute structured telephone interview with prior consent.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Congenital pulmonary airway malformation (CPAM) (previously named congenital cystic&#xD;
      adenomatoid malformation) is a rare abnormality, first described in 1949. CPAM results from&#xD;
      adenomatoid proliferation of the terminal bronchioles causing cyst formation, which may&#xD;
      impair normal alveolar growth. It occurs more commonly in males and has an estimated&#xD;
      incidence of 1:11000 to 1:35000. Most are diagnosed on routine antenatal ultrasonography.&#xD;
      Most involve lower lobes, occasionally lesions are bilateral. CPAM lesions are usually&#xD;
      managed by surgical removal in childhood due to the risk of serious infection, and potential&#xD;
      for malignant change. A recent meta-analysis has favoured surgical management.&#xD;
&#xD;
      Historically, correction of CPAM was by open thoracotomy and surgical resection. This has&#xD;
      evolved, however, and since 2008 more than 50 surgical corrections have been carried out&#xD;
      thoracoscopically at King's College Hospital. The perioperative anaesthetic management of&#xD;
      these children has also evolved, with the increasing use of selective lung ventilation.&#xD;
&#xD;
      The age range at surgery is variable, usually 1 - 14 years, and just over half being&#xD;
      asymptomatic. Anaesthetic techniques are variable: for example, the deployment of selective&#xD;
      lung ventilation techniques, the choice of anaesthetic agents and the types of invasive&#xD;
      monitoring. Surgical duration is typically 3-4 hours. A degree of hypercarbia occurs in most&#xD;
      cases during the procedure because of reduced minute ventilation to facilitate surgical&#xD;
      access, and the absorption of carbon dioxide insufflated into the pleural space. Around 1/3rd&#xD;
      receive blood transfusions. Perioperative complications include: respiratory problems causing&#xD;
      hypoxia, requirement for re-intubation, conversion to open thoracotomy, bradycardia, surgical&#xD;
      emphysema and sometimes the requirement for prolonged post-operative respiratory support&#xD;
      including ventilation, CPAP and chest drain management, bronchopulmonary fistulae, and&#xD;
      chylothorax and rarely seizures and cerebral infarction.&#xD;
&#xD;
      In general, post-operative care includes at least 24 hours critical care and another 6-7 days&#xD;
      in hospital. The mainstay of early post-operative pain control is either with morphine using&#xD;
      a nurse controlled intravenous analgesia system, or with epidural analgesia. These are&#xD;
      supplemented with oral analgesic regimens. Children who were preoperatively symptomatic seem&#xD;
      more likely to develop perioperative complications.&#xD;
&#xD;
      Objective The purpose of this investigation is to review all children who underwent CPAM&#xD;
      surgery over the last 10 years at a single regional centre and carry out a descriptive&#xD;
      evaluation of pre-operative factors, anaesthetic and surgical factors, peri- and&#xD;
      post-operative morbidity, mortality and subsequent long term outcome.&#xD;
&#xD;
      Methods A retrospective review of all CPAM resections performed since 2008 at a single&#xD;
      centre. The data will be retrieved from electronic and paper based medical records,&#xD;
      anaesthetics records and operation notes. A prospective analysis of the post-operative course&#xD;
      and events will be undertaken. A detailed evaluation of these children in relation to their&#xD;
      health, growth and development will be carried out via a structured 20-minute telephone&#xD;
      interview with prior consent.&#xD;
&#xD;
      Analysis Outcomes will be compared across preoperatively symptomatic and asymptomatic groups&#xD;
      using Mann-Whitney/Wilcoxon test or Student t test for continuous data or the chi square for&#xD;
      categorical data. All tests were 2-tailed, and P&lt; 0.05 was considered statistically&#xD;
      significant.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 10, 2018</start_date>
  <completion_date type="Actual">February 28, 2020</completion_date>
  <primary_completion_date type="Actual">September 30, 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Perioperative morbidity associated with the CPAM removal surgical episode</measure>
    <time_frame>28 days postoperative</time_frame>
    <description>This will be a descriptive measure of perioperative complications, namely, number including converted to 'open' surgery from thoracoscopy and its reasons, postoperative respiratory complications needing active therapy such as return to theatre, reintubation, insertion of chest drains to manage pneumothorax, haemothorax or chylothorax, duration of intensive care needed and duration of hospital stay needed.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Perioperative mortality associated the CPAM removal surgical episode</measure>
    <time_frame>28 days postoperative</time_frame>
    <description>This will include 28 day mortality associated with the surgical episode</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Post surgery long-term well being as reported by parents/guardian</measure>
    <time_frame>A prospective 1 year to complete a telephone follow-up of all participant children who had their surgery performed between 2007-2017</time_frame>
    <description>This will be a qualitative assessment of the child's postoperative well-being as reported by the parents/guardian during hospital follow up clinics or an assessment by telephone using a standard questionnaire to assess well-being, growth and development of the child as reported by the parents or guardian. This will in addition include the frequency of any respiratory symptoms, therapeutic needs and hospitalisations encountered by the child following the removal of CPAM.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post surgery long-term development and growth of children as reported by parent/guardian</measure>
    <time_frame>A prospective 1 year to complete a telephone follow-up of all participant children who had their surgery performed between 2007-2017</time_frame>
    <description>This will be parental opinion of child's well-being when compared to that of preoperative cognitive function, development, and general health. In summary this is a qualitative assessment of child's health as reported by the parents.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">72</enrollment>
  <condition>Pulmonary Arteriovenous Malformation</condition>
  <condition>Congenital Disorders</condition>
  <arm_group>
    <arm_group_label>1</arm_group_label>
    <description>Inclusion criteria: All consenting Infants and children who have had A Congenital Pulmonary Airway Malformation (CPAM) surgically removed by thoracoscopy over a 10 year period (2008-2017) in a regional centre.&#xD;
Exclusion criteria: Non consenting participants</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Thoracoscopic CPAM resection</intervention_name>
    <description>Surgical removal of lung lesion</description>
    <arm_group_label>1</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        All infants and children who had undergone thoracoscopic surgery for a CPAM from 2008 to&#xD;
        2017 at a regional centre&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        All children undergoing surgery for a CPAM removal between 2008 - 2017 at a regional&#xD;
        hospital.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Lack of informed consent. Inability to contact parents/guardian for the required&#xD;
        post-operative interview&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>16 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Chulananda Goonasekera</last_name>
    <role>Principal Investigator</role>
    <affiliation>Consultant Anaesthetist</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Kings College Hospital NHS Trust</name>
      <address>
        <city>London</city>
        <zip>SE5 9RS</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <reference>
    <citation>Subramanyam R, Ledbetter K, Fleck R, Mahmoud M. Images in Anesthesiology: Congenital Pulmonary Airway Malformation. Anesthesiology. 2017 Aug;127(2):382. doi: 10.1097/ALN.0000000000001602. No abstract available.</citation>
    <PMID>28719530</PMID>
  </reference>
  <reference>
    <citation>Cloutier MM, Schaeffer DA, Hight D. Congenital cystic adenomatoid malformation. Chest. 1993 Mar;103(3):761-4. doi: 10.1378/chest.103.3.761.</citation>
    <PMID>8449065</PMID>
  </reference>
  <reference>
    <citation>Sfakianaki AK, Copel JA. Congenital cystic lesions of the lung: congenital cystic adenomatoid malformation and bronchopulmonary sequestration. Rev Obstet Gynecol. 2012;5(2):85-93.</citation>
    <PMID>22866187</PMID>
  </reference>
  <reference>
    <citation>Mann S, Wilson RD, Bebbington MW, Adzick NS, Johnson MP. Antenatal diagnosis and management of congenital cystic adenomatoid malformation. Semin Fetal Neonatal Med. 2007 Dec;12(6):477-81. doi: 10.1016/j.siny.2007.06.009. Epub 2007 Oct 22.</citation>
    <PMID>17950681</PMID>
  </reference>
  <reference>
    <citation>David M, Lamas-Pinheiro R, Henriques-Coelho T. Prenatal and Postnatal Management of Congenital Pulmonary Airway Malformation. Neonatology. 2016;110(2):101-15. doi: 10.1159/000440894. Epub 2016 Apr 13.</citation>
    <PMID>27070354</PMID>
  </reference>
  <results_reference>
    <citation>Sueyoshi R, Koga H, Suzuki K, Miyano G, Okawada M, Doi T, Lane GJ, Yamataka A. Surgical intervention for congenital pulmonary airway malformation (CPAM) patients with preoperative pneumonia and abscess formation: &quot;open versus thoracoscopic lobectomy&quot;. Pediatr Surg Int. 2016 Apr;32(4):347-51. doi: 10.1007/s00383-015-3848-z. Epub 2015 Dec 12.</citation>
    <PMID>26661941</PMID>
  </results_reference>
  <results_reference>
    <citation>CH'IN KY, TANG MY. Congenital adenomatoid malformation of one lobe of a lung with general anasarca. Arch Pathol (Chic). 1949 Sep;48(3):221-9. No abstract available.</citation>
    <PMID>18137795</PMID>
  </results_reference>
  <results_reference>
    <citation>Laberge JM, Flageole H, Pugash D, Khalife S, Blair G, Filiatrault D, Russo P, Lees G, Wilson RD. Outcome of the prenatally diagnosed congenital cystic adenomatoid lung malformation: a Canadian experience. Fetal Diagn Ther. 2001 May-Jun;16(3):178-86. doi: 10.1159/000053905.</citation>
    <PMID>11316935</PMID>
  </results_reference>
  <results_reference>
    <citation>Kapralik J, Wayne C, Chan E, Nasr A. Surgical versus conservative management of congenital pulmonary airway malformation in children: A systematic review and meta-analysis. J Pediatr Surg. 2016 Mar;51(3):508-12. doi: 10.1016/j.jpedsurg.2015.11.022. Epub 2015 Dec 9.</citation>
    <PMID>26775193</PMID>
  </results_reference>
  <verification_date>April 2018</verification_date>
  <study_first_submitted>October 10, 2018</study_first_submitted>
  <study_first_submitted_qc>June 23, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 29, 2020</study_first_posted>
  <last_update_submitted>June 23, 2020</last_update_submitted>
  <last_update_submitted_qc>June 23, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 29, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cystic Adenomatoid Malformation of Lung, Congenital</mesh_term>
    <mesh_term>Arteriovenous Malformations</mesh_term>
    <mesh_term>Congenital Abnormalities</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>April 24, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/14/NCT04449614/ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT04449614
org study id: IRAS 238420
nct id: NCT04449614
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Congenital pulmonary malformation in children is a rare abnormality mostly diagnosed before
      birth during antenatal ultrasound examinations. These lesions may expand to form lung cysts
      in children, cause recurrent lung infections and has a potential for malignant change.
      Therefore, surgical removal in childhood is favoured as the treatment of choice.

      The surgical correction may involve 'open' surgery or 'key hole' surgery. There is, however,
      a variation in surgical and anaesthetic techniques and timing of this surgery and subsequent
      complications reported post-surgery.

      The purpose of this investigation is to review anaesthetic and surgical case notes and the
      subsequent well-being of all children who underwent lung surgery to remove above lung lesions
      over the last 10 years (2008-2017) at a regional centre. The aim is to look at the current
      status of these children in relation to their health, growth and development evaluated via a
      20-minute structured telephone interview with prior consent.
Congenital pulmonary airway malformation (CPAM) (previously named congenital cystic
      adenomatoid malformation) is a rare abnormality, first described in 1949. CPAM results from
      adenomatoid proliferation of the terminal bronchioles causing cyst formation, which may
      impair normal alveolar growth. It occurs more commonly in males and has an estimated
      incidence of 1:11000 to 1:35000. Most are diagnosed on routine antenatal ultrasonography.
      Most involve lower lobes, occasionally lesions are bilateral. CPAM lesions are usually
      managed by surgical removal in childhood due to the risk of serious infection, and potential
      for malignant change. A recent meta-analysis has favoured surgical management.

      Historically, correction of CPAM was by open thoracotomy and surgical resection. This has
      evolved, however, and since 2008 more than 50 surgical corrections have been carried out
      thoracoscopically at King's College Hospital. The perioperative anaesthetic management of
      these children has also evolved, with the increasing use of selective lung ventilation.

      The age range at surgery is variable, usually 1 - 14 years, and just over half being
      asymptomatic. Anaesthetic techniques are variable: for example, the deployment of selective
      lung ventilation techniques, the choice of anaesthetic agents and the types of invasive
      monitoring. Surgical duration is typically 3-4 hours. A degree of hypercarbia occurs in most
      cases during the procedure because of reduced minute ventilation to facilitate surgical
      access, and the absorption of carbon dioxide insufflated into the pleural space. Around 1/3rd
      receive blood transfusions. Perioperative complications include: respiratory problems causing
      hypoxia, requirement for re-intubation, conversion to open thoracotomy, bradycardia, surgical
      emphysema and sometimes the requirement for prolonged post-operative respiratory support
      including ventilation, CPAP and chest drain management, bronchopulmonary fistulae, and
      chylothorax and rarely seizures and cerebral infarction.

      In general, post-operative care includes at least 24 hours critical care and another 6-7 days
      in hospital. The mainstay of early post-operative pain control is either with morphine using
      a nurse controlled intravenous analgesia system, or with epidural analgesia. These are
      supplemented with oral analgesic regimens. Children who were preoperatively symptomatic seem
      more likely to develop perioperative complications.

      Objective The purpose of this investigation is to review all children who underwent CPAM
      surgery over the last 10 years at a single regional centre and carry out a descriptive
      evaluation of pre-operative factors, anaesthetic and surgical factors, peri- and
      post-operative morbidity, mortality and subsequent long term outcome.

      Methods A retrospective review of all CPAM resections performed since 2008 at a single
      centre. The data will be retrieved from electronic and paper based medical records,
      anaesthetics records and operation notes. A prospective analysis of the post-operative course
      and events will be undertaken. A detailed evaluation of these children in relation to their
      health, growth and development will be carried out via a structured 20-minute telephone
      interview with prior consent.

      Analysis Outcomes will be compared across preoperatively symptomatic and asymptomatic groups
      using Mann-Whitney/Wilcoxon test or Student t test for continuous data or the chi square for
      categorical data. All tests were 2-tailed, and P< 0.05 was considered statistically
      significant.
observational model: Cohort
time perspective: Retrospective
measure: Perioperative morbidity associated with the CPAM removal surgical episode
time frame: 28 days postoperative
description: This will be a descriptive measure of perioperative complications, namely, number including converted to 'open' surgery from thoracoscopy and its reasons, postoperative respiratory complications needing active therapy such as return to theatre, reintubation, insertion of chest drains to manage pneumothorax, haemothorax or chylothorax, duration of intensive care needed and duration of hospital stay needed.
measure: Perioperative mortality associated the CPAM removal surgical episode
time frame: 28 days postoperative
description: This will include 28 day mortality associated with the surgical episode
measure: Post surgery long-term well being as reported by parents/guardian
time frame: A prospective 1 year to complete a telephone follow-up of all participant children who had their surgery performed between 2007-2017
description: This will be a qualitative assessment of the child's postoperative well-being as reported by the parents/guardian during hospital follow up clinics or an assessment by telephone using a standard questionnaire to assess well-being, growth and development of the child as reported by the parents or guardian. This will in addition include the frequency of any respiratory symptoms, therapeutic needs and hospitalisations encountered by the child following the removal of CPAM.
measure: Post surgery long-term development and growth of children as reported by parent/guardian
time frame: A prospective 1 year to complete a telephone follow-up of all participant children who had their surgery performed between 2007-2017
description: This will be parental opinion of child's well-being when compared to that of preoperative cognitive function, development, and general health. In summary this is a qualitative assessment of child's health as reported by the parents.
arm group label: 1
description: Inclusion criteria: All consenting Infants and children who have had A Congenital Pulmonary Airway Malformation (CPAM) surgically removed by thoracoscopy over a 10 year period (2008-2017) in a regional centre.
Exclusion criteria: Non consenting participants
intervention type: Procedure
intervention name: Thoracoscopic CPAM resection
description: Surgical removal of lung lesion
arm group label: 1
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: 16 Years
healthy volunteers: No
last name: Chulananda Goonasekera
role: Principal Investigator
affiliation: Consultant Anaesthetist
facility: 
country: United Kingdom
citation: Subramanyam R, Ledbetter K, Fleck R, Mahmoud M. Images in Anesthesiology: Congenital Pulmonary Airway Malformation. Anesthesiology. 2017 Aug;127(2):382. doi: 10.1097/ALN.0000000000001602. No abstract available.
PMID: 28719530
citation: Cloutier MM, Schaeffer DA, Hight D. Congenital cystic adenomatoid malformation. Chest. 1993 Mar;103(3):761-4. doi: 10.1378/chest.103.3.761.
PMID: 8449065
citation: Sfakianaki AK, Copel JA. Congenital cystic lesions of the lung: congenital cystic adenomatoid malformation and bronchopulmonary sequestration. Rev Obstet Gynecol. 2012;5(2):85-93.
PMID: 22866187
citation: Mann S, Wilson RD, Bebbington MW, Adzick NS, Johnson MP. Antenatal diagnosis and management of congenital cystic adenomatoid malformation. Semin Fetal Neonatal Med. 2007 Dec;12(6):477-81. doi: 10.1016/j.siny.2007.06.009. Epub 2007 Oct 22.
PMID: 17950681
citation: David M, Lamas-Pinheiro R, Henriques-Coelho T. Prenatal and Postnatal Management of Congenital Pulmonary Airway Malformation. Neonatology. 2016;110(2):101-15. doi: 10.1159/000440894. Epub 2016 Apr 13.
PMID: 27070354
citation: Sueyoshi R, Koga H, Suzuki K, Miyano G, Okawada M, Doi T, Lane GJ, Yamataka A. Surgical intervention for congenital pulmonary airway malformation (CPAM) patients with preoperative pneumonia and abscess formation: "open versus thoracoscopic lobectomy". Pediatr Surg Int. 2016 Apr;32(4):347-51. doi: 10.1007/s00383-015-3848-z. Epub 2015 Dec 12.
PMID: 26661941
citation: CH'IN KY, TANG MY. Congenital adenomatoid malformation of one lobe of a lung with general anasarca. Arch Pathol (Chic). 1949 Sep;48(3):221-9. No abstract available.
PMID: 18137795
citation: Laberge JM, Flageole H, Pugash D, Khalife S, Blair G, Filiatrault D, Russo P, Lees G, Wilson RD. Outcome of the prenatally diagnosed congenital cystic adenomatoid lung malformation: a Canadian experience. Fetal Diagn Ther. 2001 May-Jun;16(3):178-86. doi: 10.1159/000053905.
PMID: 11316935
citation: Kapralik J, Wayne C, Chan E, Nasr A. Surgical versus conservative management of congenital pulmonary airway malformation in children: A systematic review and meta-analysis. J Pediatr Surg. 2016 Mar;51(3):508-12. doi: 10.1016/j.jpedsurg.2015.11.022. Epub 2015 Dec 9.
PMID: 26775193
responsible party type: Sponsor
mesh term: Cystic Adenomatoid Malformation of Lung, Congenital
mesh term: Arteriovenous Malformations
mesh term: Congenital Abnormalities
sharing ipd: Undecided
provided document: 