<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/NCT03788122</url>
  </required_header>
  <id_info>
    <org_study_id>S61586</org_study_id>
    <nct_id>NCT03788122</nct_id>
  </id_info>
  <brief_title>Fetal Surgery Interview Study: Parental Perceptions of Fetal Surgery</brief_title>
  <official_title>Qualitative In-depth Interviews With Women and Their Partners Concerning the Acceptability of Fetal Surgery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universitaire Ziekenhuizen KU Leuven</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University College, London</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Wellcome Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Universitaire Ziekenhuizen KU Leuven</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>
      Open maternal-fetal surgery is currently used on fetuses with myelomeningocele (MMC).&#xD;
      Fetoscopic or minimal access fetal surgery is also being used to treat fetuses with&#xD;
      congenital diaphragmatic hernia (CDH).&#xD;
&#xD;
      Following accurate diagnosis of a congenital malformation such as MMC or CDH, prospective&#xD;
      parents face a range of uncertainties regarding the future of their unborn child, and the&#xD;
      options provided require major ethical considerations. In the situation under study,&#xD;
      termination of pregnancy may be for some parents an alternative option to expectant prenatal&#xD;
      management. Fetal therapy provides a tantalising third option for some, where procedures are&#xD;
      undertaken to reduce the likelihood of a more complicated neonatal course, potentially&#xD;
      improving long term outcome, but at risk of amniotic fluid leakage, infection and most&#xD;
      importantly very preterm delivery, itself associated with significant neonatal mortality and&#xD;
      morbidity and long-term consequences. Balancing these competing risks is challenging.&#xD;
&#xD;
      For an intervention to be effective it also needs to be acceptable to women and their&#xD;
      families. &quot;Acceptability&quot; can be defined as a multi-faceted construct that reflects the&#xD;
      extent to which people delivering or receiving a healthcare intervention consider it to be&#xD;
      appropriate, based on anticipated or experienced cognitive and emotional responses to the&#xD;
      intervention.&#xD;
&#xD;
      With this study it is the aim to assess how women (and their partners) perceive the&#xD;
      acceptability of a fetal surgical intervention for MMC and CDH. Participants will be asked to&#xD;
      share their thoughts, views, feelings and experiences with regards to the decision to&#xD;
      participate in fetal surgery. Data are collected by the use of in-depth face-to-face&#xD;
      interviews. In-depth interviews are used to understand the participant's perspectives and&#xD;
      perceptions of a situation they are in. It explicitly includes participants interpretation&#xD;
      and understanding of an event&#xD;
&#xD;
      The interviews will be held in two or three moments in time (for parents opting for fetal&#xD;
      surgery, there will be one additional interview, after the intervention while admitted in&#xD;
      hospital): after counselling for options, but before eventual intervention; for intervention&#xD;
      group shortly after the intervention, and 12 weeks after birth of the baby, or termination of&#xD;
      pregnancy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      1. Background and rationale Fetal surgery is a highly technical procedure carried out by&#xD;
           only a few specialised teams around the world. Fetal surgery improves outcomes for key&#xD;
           conditions, but at significant procedure related fetal and maternal risk. Open&#xD;
           maternal-fetal surgery is currently used on fetuses with myelomeningocele (MMC).&#xD;
           Fetoscopic or minimal access fetal surgery is also being used to treat fetuses with&#xD;
           congenital diaphragmatic hernia (CDH). By combining improved instrumentation, imaging,&#xD;
           clinical training and public engagement The Guided Instrumentation for Fetal Therapy and&#xD;
           Surgery (GIFT-Surg) project aims to provide fetal surgeons with tools to make fetal&#xD;
           surgery safer and more efficient. The UZ and KU Leuven team participates in this&#xD;
           engineering project.&#xD;
&#xD;
           Following accurate diagnosis of a congenital malformation such as MMC or CDH,&#xD;
           prospective parents face a range of uncertainties regarding the future of their unborn&#xD;
           child, and the options provided require major ethical considerations. In the situation&#xD;
           under study, termination of pregnancy may be for some parents an alternative option to&#xD;
           expectant prenatal management. Fetal therapy provides a tantalising third option for&#xD;
           some, where procedures are undertaken to reduce the likelihood of a more complicated&#xD;
           neonatal course, potentially improving long term outcome, but at risk of amniotic fluid&#xD;
           leakage, infection and most importantly very preterm delivery, associated with&#xD;
           significant neonatal mortality and morbidity and long-term consequences. Balancing these&#xD;
           competing risks is challenging.&#xD;
&#xD;
             1. Myelomeningocele Prevalence, incidence, clinical presentation Myelomeningocele&#xD;
                (MMC) or spina bifida is a congenital abnormality arising 28 days post-conception&#xD;
                when part of the neural tube fails to close. Open spina bifida can present either&#xD;
                with a flat defect without a fluid filled sac covering (myeloschisis), or&#xD;
                membranous covering with extrusion of the cord into the sac (myelomeningocele). Its&#xD;
                prevalence is approximately 4.9 per 10,000 live births in Europe. Myelomeningocele&#xD;
                is a severe, yet non-lethal congenital abnormality affecting the central nervous&#xD;
                system, with complex physical and neurodevelopmental sequelae. In most cases it is&#xD;
                also associated with the Chiari Type II malformation (hindbrain herniation) and&#xD;
                ventriculomegaly.&#xD;
&#xD;
                Therapy, risks and (long-term) outcome Until recently, the only options available&#xD;
                to parents, once a diagnosis was made prenatally, were expectant management with&#xD;
                delivery and postnatal surgery, or a pregnancy termination. But over the last&#xD;
                thirty years, it became obvious that the condition is progressive in utero, as is&#xD;
                suggested by the &quot;two-hit&quot; hypothesis; an initial embryonic failure in neurulation&#xD;
                followed by secondary changes because of continuous exposure of the spinal cord to&#xD;
                the intrauterine environment and the suction gradient on the hindbrain. This led to&#xD;
                the concept of fetal intervention to arrest or reverse this natural course.&#xD;
                Successful fetal coverage of MMC with improved functional outcome in the lamb model&#xD;
                was first described in the late 1990s. This was translated clinically with&#xD;
                encouraging early results in several case series and eventually led to the&#xD;
                randomized controlled Management of Myelomeningocele Study (MOMS). This study&#xD;
                demonstrated that mid-gestational layered repair reduces the need for&#xD;
                ventriculoperitoneal shunting, improves the degree of hindbrain herniation, and&#xD;
                preserves motor function better than postnatal surgery. However, fetal surgery for&#xD;
                spina bifida comes with substantial maternal and fetal risks. The fetus is at&#xD;
                increased risk of premature birth and its sequelae including sepsis,&#xD;
                intraventricular haemorrhage, respiratory distress syndrome, necrotizing&#xD;
                enterocolitis and death. Besides there is the risk for maternal complications and&#xD;
                the corporeal scar compromises uterine integrity.&#xD;
&#xD;
             2. Congenital diaphragmatic hernia Prevalence, incidence, clinical presentation Due to&#xD;
                a defect in the diaphragm during embryonic development, abdominal organs herniate&#xD;
                through the defect into the thoracic cavity, interfering with lung growth,&#xD;
                resulting in developmental arrest of both airways and pulmonary vasculature.&#xD;
                Congenital diaphragmatic hernia (CDH) occurs in 1/2500 to 1/5000 births, depending&#xD;
                on whether stillbirths are included. Although the diaphragmatic defect is&#xD;
                correctable after birth, the prenatal arrest of airway and vessel development is&#xD;
                the main reason for postnatal problems, leading to respiratory failure and&#xD;
                pulmonary hypertension (PHT) in the neonatal period. Although prenatal referral to&#xD;
                specialist centers, high throughput and advanced neonatal care has improved&#xD;
                survival, still 20-30% of all cases die. Besides, survivors experience ongoing&#xD;
                pulmonary and nutritional morbidity.&#xD;
&#xD;
                Therapy, risks and (long-term) outcome In fetuses with poor prognosis, fetal lung&#xD;
                growth can be stimulated by fetoscopic endoluminal tracheal occlusion (FETO) with a&#xD;
                balloon. The fetal lung is a net secretor of fluid into the amniotic cavity and the&#xD;
                lungs are maintained at a small positive pressure in normal development. Fetal&#xD;
                tracheal occlusion (TO) prevents egress of lung liquid, leading to increased back&#xD;
                pressure, in turn promoting stretch-induced growth of airways and vessels. TO&#xD;
                appears to trigger sufficient lung growth to protect the lung from developing&#xD;
                pulmonary hypoplasia. In utero reversal of the occlusion prompts pulmonary&#xD;
                maturation. Experimentally an endoscopic technique of tracheal occlusion using a&#xD;
                balloon was developed. In 2004, it was first applied clinically and referred to as&#xD;
                Fetoscopic Endoluminal Tracheal Occlusion (FETO).&#xD;
&#xD;
                The major risk following the procedure is spontaneous pre-labour rupture of&#xD;
                membranes before 37 weeks (PPROM). Gestational age at delivery logically is an&#xD;
                important predictor of survival and morbidity in CDH fetuses, also when undergoing&#xD;
                fetal therapy.&#xD;
&#xD;
                A meta-analysis suggests that FETO improves survival, but the procedure remains to&#xD;
                be considered investigational and is therefore currently evaluated within a&#xD;
                randomized controlled clinical trial (www.totaltrial.eu).&#xD;
&#xD;
             3. Acceptability For an intervention to be effective it also needs to be acceptable to&#xD;
                women and their families. &quot;Acceptability&quot; can be defined as a multi-faceted&#xD;
                construct that reflects the extent to which people delivering or receiving a&#xD;
                healthcare intervention consider it to be appropriate, based on anticipated or&#xD;
                experienced cognitive and emotional responses to the intervention. Based on this&#xD;
                definition a theoretical framework of acceptability comprising seven components has&#xD;
                been developed: affective attitude, burden, perceived effectiveness, ethicality,&#xD;
                intervention coherence, opportunity costs, and self-efficacy. Successful&#xD;
                implementation of an intervention means that it is acceptable for both recipients&#xD;
                and deliverers. This study focuses on the recipients; measurement of acceptability&#xD;
                for deliverers will be considered as other facets of the wider GIFT-Surg project.&#xD;
&#xD;
           Timing is an important factor in the assessment as the relationship to perceived and&#xD;
           actual experiences may differ. Acceptability is therefore assessed in two or three&#xD;
           moments in time: prospective acceptability, concurrent acceptability and retrospective&#xD;
           acceptability.&#xD;
&#xD;
        2. Trial objectives&#xD;
&#xD;
           Primary objective: to assess how women (and their partners) perceive the acceptability&#xD;
           of a fetal surgical intervention for MMC and CDH. Participants will be asked to share&#xD;
           their thoughts, views, feelings and experiences with regards to the decision to&#xD;
           participate in fetal surgery.&#xD;
&#xD;
        3. Trial Design&#xD;
&#xD;
           This is a qualitative in-depth interview study, to include approximately 48&#xD;
           women/couples at University Hospital Leuven for two fetal conditions (MMC and CDH),&#xD;
           given all data on these 48 patients are complete. An estimated dropout rate of 50% means&#xD;
           that in total 4 patients per treatment option (fetal surgery, expectant management,&#xD;
           termination), and per condition (MMC or CDH) will be available for analysis.&#xD;
&#xD;
           As not all parents opt for fetal surgery, after referral and counselling for prenatal&#xD;
           diagnosed isolated spinal defects and congenital diaphragmatic hernia, patients fall&#xD;
           into three groups: 1. Parents opting for fetal surgery, 2. Parents opting for&#xD;
           termination of pregnancy and 3. Parents opting for expectant management. To assess&#xD;
           acceptability of the intervention, it is of value to assess acceptability of the&#xD;
           intervention in all three groups. In particular, knowledge of non-acceptability&#xD;
           important.&#xD;
&#xD;
        4. Trial Intervention&#xD;
&#xD;
           Data collection will take place by executing face-to-face interviews. The interviews&#xD;
           will be held in three moments in time: before, during (i.e. shortly after the&#xD;
           intervention) and after the intervention. Prospective acceptability will be assessed,&#xD;
           after patients have been first counselled and assessed, but before the intervention at&#xD;
           stake. Concurrent acceptability, patients will be interviewed shortly after the&#xD;
           intervention while still admitted for post-surgery observation, and retrospective&#xD;
           acceptability three months after delivery.&#xD;
&#xD;
           The interviews assessing prospective and concurrent acceptability will always be planned&#xD;
           along visits to the treatment hospital so parents never have to come on purpose to the&#xD;
           hospital for an interview, and will be held in Dutch or English. The interviews are&#xD;
           expected to last approximately 30-60 minutes and will follow an interview guide. As it&#xD;
           is acknowledged women (and their partners) go through an intensive and emotionally&#xD;
           upsetting process, interviews will only be carried out if the patient is capable of&#xD;
           participating in an interview, based on the patient's personal assessment as well as&#xD;
           their doctor's assessment. For retrospective acceptability, depending on participant's&#xD;
           preference, the interview can take place through teleconference or phone.&#xD;
&#xD;
           Data-collection Data are collected by the use of in-depth interviews. In-depth&#xD;
           interviews are used to understand the participant's perspectives and perceptions of a&#xD;
           situation they are in. It explicitly includes participants interpretation and&#xD;
           understanding of an event. The style of interviewing will be 'responsive'; this style&#xD;
           emphasises on the importance of building a relationship of trust between interviewer and&#xD;
           interviewee. This is done by creating a quiet and calm environment, an empathically&#xD;
           neutral position of the interviewer and an open approach by using verbal and non-verbal&#xD;
           communication. There will not be a set list of questions, but an interview guide based&#xD;
           on one main-question, with different themes for probing, based on the seven components&#xD;
           of the framework of acceptability. The interview will follow six stages as described by&#xD;
           Yeo et al.: arrival and introduction: establish rapport, 'host' the interaction(stage&#xD;
           1); introducing the research (aims and objectives, confidentiality, voluntary, scope of&#xD;
           interview (participant in control), no right or wrong answers(stage 2); beginning of the&#xD;
           interview: discuss contextual background information for reference and set the tone&#xD;
           (stage 3); during the interview (start recording: breadth and depth of subject)(stage&#xD;
           4); ending the interview: advance notice of end and opportunity for respondent to raise&#xD;
           anything important not yet discussed (stage 5); and after the interview: thanking and&#xD;
           emphasize on value of sharing their experience, how information is treated and used,&#xD;
           follow up and further meetings to be scheduled (stage 6)(interview guide).&#xD;
&#xD;
           The interviews will be recorded digitally with an audio recorder. Subsequently,&#xD;
           interviews will be transcribed and coded transcripts will be translated into English and&#xD;
           used for analysis. Back-translation will be used for a sample of 5 transcripts in Dutch&#xD;
           to ensure accuracy.&#xD;
&#xD;
        5. Sample size&#xD;
&#xD;
           Intended sample size in Belgium is 12 women for MMC and 12 for CDH at study completion;&#xD;
           in the UK the investigators expect to include 10 women for MMC and 5 for CDH. This&#xD;
           sample size has been determined from interviewing clinical stakeholders. Sample size in&#xD;
           qualitative research are usually small, as in analysis there will be at some point a&#xD;
           moment in which no new information is obtained from additional interviews. This is also&#xD;
           called saturation. The aim of this research is not to determine statistically&#xD;
           significant discriminatory variables, but to get an in-depth understanding of the views&#xD;
           and preferences of the participants, and to assess acceptability of the intervention.&#xD;
           Exact sample size will depend on saturation&#xD;
&#xD;
        6. Analysis&#xD;
&#xD;
      The analysis is purely qualitative. The interviews will be transcribed verbatim by the&#xD;
      researcher. Content analyses will be performed by using the qualitative software programme.&#xD;
      First, initial content and subjects of interest are identified, the so-called familiarization&#xD;
      with the data. This first step is followed by the initial construct of a framework. The&#xD;
      framework constructs the headings under which respondent's views, feelings, experiences and&#xD;
      perceptions can be organized. The framework is than used for labelling the data: quotes or&#xD;
      pieces of text are ordered according to the different themes to fit in. The next step will be&#xD;
      further refinement of the framework by making connections between categories and placing them&#xD;
      in a broader context related to the framework of acceptability. To improve the quality of the&#xD;
      analysis, at various moments interim analyses will be discussed among co-authors with a&#xD;
      background in psychology and qualitative analysis. Thereafter, all previously analyzed&#xD;
      transcripts will be reviewed to check that the content is consistent with this concept&#xD;
      (thematic analysis).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">July 1, 2018</start_date>
  <completion_date type="Anticipated">March 2020</completion_date>
  <primary_completion_date type="Anticipated">March 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Prospective acceptability of fetal surgery in the context of Myelomeningocele and Congenital Diaphragmatic Hernia.</measure>
    <time_frame>After evaluation and counseling, if applicable, before undergoing fetal surgery.</time_frame>
    <description>Qualitative methodology. Prospective acceptability, as perceived by prospective parents eligible for fetal surgery, assessed by in-depth face-to face interviews.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Concurrent acceptability of fetal surgery in the context of Myelomeningocele and Congenital Diaphragmatic Hernia.</measure>
    <time_frame>After fetal surgery, within 7 days after surgery.</time_frame>
    <description>Qualitative methodology. Concurrent acceptability, as perceived by prospective parents eligible for fetal surgery, assessed by in-depth face-to face interviews.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Retrospective acceptability of fetal surgery in the context of Myelomeningocele and Congenital Diaphragmatic Hernia.</measure>
    <time_frame>Three months after birth of the baby, or three months after termination of the pregnancy.</time_frame>
    <description>Qualitative methodology. Retrospective acceptability, as perceived by prospective parents eligible for fetal surgery, assessed by in-depth face-to face interviews.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Fetal Surgery</condition>
  <condition>Myelomeningocele</condition>
  <condition>Congenital Diaphragmatic Hernia</condition>
  <arm_group>
    <arm_group_label>Parents eligible for fetal surgery</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Parents eligible for fetal surgery will undergo two or three in-depth face-tot-face interviews, to determine their perception of acceptability of fetal surgery.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>In-depth interview</intervention_name>
    <description>The 'intervention' administered to this group of participants are two or three in-depth interviews (average 30-60 m minutes per interview) on their experiences, views, feelings and thoughts (perceptions) regarding acceptability of the fetal surgery.</description>
    <arm_group_label>Parents eligible for fetal surgery</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Women/partners eligible for one of the two fetal surgery procedures studied (open&#xD;
             fetal surgery for spina bifida closure, tracheal balloon occlusion for congenital&#xD;
             diaphragmatic hernia (Fetoscopic Endoluminal Tracheal Occlusion, FETO), as clinical&#xD;
             care&#xD;
&#xD;
          -  Have given written informed consent for participation&#xD;
&#xD;
        Exclusion:&#xD;
&#xD;
          -  Women less than 18 years or over 65 years of age&#xD;
&#xD;
          -  Partners less than 18 years or over 65 years of age&#xD;
&#xD;
          -  Women or their partners who are unable to communicate in either English or the local&#xD;
             language (if different)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jan Deprest, Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Universitaire Ziekenhuizen KU Leuven</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Neil Marlow</last_name>
    <role>Principal Investigator</role>
    <affiliation>University College London Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jan Deprest, Professor</last_name>
    <phone>+3216 34 42 11</phone>
    <phone_ext>44211</phone_ext>
    <email>jan.deprest@uzleuven.be</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Neeltje Crombag, Dr</last_name>
    <phone>+3216 34 52 22</phone>
    <phone_ext>45222</phone_ext>
    <email>neeltje.crombag@kuleuven.be</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University Hospital Leuven</name>
      <address>
        <city>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jan Deprest, Professor</last_name>
      <phone>+3216 34 42 11</phone>
      <email>jan.deprest@uzleuven.be</email>
    </contact>
    <contact_backup>
      <last_name>Neeltje Crombag, Dr</last_name>
      <phone>+3216 34 52 22</phone>
      <email>neeltje.crombag@kuleuven.be</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>University College London Hospital</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Neil Marlow, Professor</last_name>
      <phone>+44(0)2076790834</phone>
      <email>n.marlow@ucl.ac.uk</email>
    </contact>
    <contact_backup>
      <last_name>Anna David, Professor</last_name>
      <phone>+44(0)2076796060</phone>
      <email>a.david@ucl.ac.uk</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>United Kingdom</country>
  </location_countries>
  <reference>
    <citation>Cohen AR, Couto J, Cummings JJ, Johnson A, Joseph G, Kaufman BA, Litman RS, Menard MK, Moldenhauer JS, Pringle KC, Schwartz MZ, Walker WO Jr, Warf BC, Wax JR; MMC Maternal-Fetal Management Task Force. Position statement on fetal myelomeningocele repair. Am J Obstet Gynecol. 2014 Feb;210(2):107-11. doi: 10.1016/j.ajog.2013.09.016. Epub 2013 Sep 18.</citation>
    <PMID>24055581</PMID>
  </reference>
  <reference>
    <citation>Deprest J, Nicolaides K, Done' E, Lewi P, Barki G, Largen E, DeKoninck P, Sandaite I, Ville Y, Benachi A, Jani J, Amat-Roldan I, Gratacos E. Technical aspects of fetal endoscopic tracheal occlusion for congenital diaphragmatic hernia. J Pediatr Surg. 2011 Jan;46(1):22-32. doi: 10.1016/j.jpedsurg.2010.10.008.</citation>
    <PMID>21238635</PMID>
  </reference>
  <reference>
    <citation>Ville Y. Fetal therapy: practical ethical considerations. Prenat Diagn. 2011 Jul;31(7):621-7. doi: 10.1002/pd.2808. Epub 2011 Jun 10.</citation>
    <PMID>21660998</PMID>
  </reference>
  <reference>
    <citation>Adzick NS, Thom EA, Spong CY, Brock JW 3rd, Burrows PK, Johnson MP, Howell LJ, Farrell JA, Dabrowiak ME, Sutton LN, Gupta N, Tulipan NB, D'Alton ME, Farmer DL; MOMS Investigators. A randomized trial of prenatal versus postnatal repair of myelomeningocele. N Engl J Med. 2011 Mar 17;364(11):993-1004. doi: 10.1056/NEJMoa1014379. Epub 2011 Feb 9.</citation>
    <PMID>21306277</PMID>
  </reference>
  <reference>
    <citation>Al-Maary J, Eastwood MP, Russo FM, Deprest JA, Keijzer R. Fetal Tracheal Occlusion for Severe Pulmonary Hypoplasia in Isolated Congenital Diaphragmatic Hernia: A Systematic Review and Meta-analysis of Survival. Ann Surg. 2016 Dec;264(6):929-933. doi: 10.1097/SLA.0000000000001675.</citation>
    <PMID>26910202</PMID>
  </reference>
  <reference>
    <citation>Sekhon M, Cartwright M, Francis JJ. Acceptability of healthcare interventions: an overview of reviews and development of a theoretical framework. BMC Health Serv Res. 2017 Jan 26;17(1):88. doi: 10.1186/s12913-017-2031-8.</citation>
    <PMID>28126032</PMID>
  </reference>
  <reference>
    <citation>Farmer DL, Thom EA, Brock JW 3rd, Burrows PK, Johnson MP, Howell LJ, Farrell JA, Gupta N, Adzick NS; Management of Myelomeningocele Study Investigators. The Management of Myelomeningocele Study: full cohort 30-month pediatric outcomes. Am J Obstet Gynecol. 2018 Feb;218(2):256.e1-256.e13. doi: 10.1016/j.ajog.2017.12.001. Epub 2017 Dec 12.</citation>
    <PMID>29246577</PMID>
  </reference>
  <reference>
    <citation>Johnson MP, Bennett KA, Rand L, Burrows PK, Thom EA, Howell LJ, Farrell JA, Dabrowiak ME, Brock JW 3rd, Farmer DL, Adzick NS; Management of Myelomeningocele Study Investigators. The Management of Myelomeningocele Study: obstetrical outcomes and risk factors for obstetrical complications following prenatal surgery. Am J Obstet Gynecol. 2016 Dec;215(6):778.e1-778.e9. doi: 10.1016/j.ajog.2016.07.052. Epub 2016 Aug 2.</citation>
    <PMID>27496687</PMID>
  </reference>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>December 13, 2018</study_first_submitted>
  <study_first_submitted_qc>December 21, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 27, 2018</study_first_posted>
  <last_update_submitted>December 21, 2018</last_update_submitted>
  <last_update_submitted_qc>December 21, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 27, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Acceptability</keyword>
  <keyword>Qualitative research</keyword>
  <keyword>Patient Perspectives</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Meningomyelocele</mesh_term>
    <mesh_term>Spina Bifida Cystica</mesh_term>
    <mesh_term>Hernias, Diaphragmatic, Congenital</mesh_term>
    <mesh_term>Hernia, Diaphragmatic</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03788122
org study id: S61586
nct id: NCT03788122
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Open maternal-fetal surgery is currently used on fetuses with myelomeningocele (MMC).
      Fetoscopic or minimal access fetal surgery is also being used to treat fetuses with
      congenital diaphragmatic hernia (CDH).

      Following accurate diagnosis of a congenital malformation such as MMC or CDH, prospective
      parents face a range of uncertainties regarding the future of their unborn child, and the
      options provided require major ethical considerations. In the situation under study,
      termination of pregnancy may be for some parents an alternative option to expectant prenatal
      management. Fetal therapy provides a tantalising third option for some, where procedures are
      undertaken to reduce the likelihood of a more complicated neonatal course, potentially
      improving long term outcome, but at risk of amniotic fluid leakage, infection and most
      importantly very preterm delivery, itself associated with significant neonatal mortality and
      morbidity and long-term consequences. Balancing these competing risks is challenging.

      For an intervention to be effective it also needs to be acceptable to women and their
      families. "Acceptability" can be defined as a multi-faceted construct that reflects the
      extent to which people delivering or receiving a healthcare intervention consider it to be
      appropriate, based on anticipated or experienced cognitive and emotional responses to the
      intervention.

      With this study it is the aim to assess how women (and their partners) perceive the
      acceptability of a fetal surgical intervention for MMC and CDH. Participants will be asked to
      share their thoughts, views, feelings and experiences with regards to the decision to
      participate in fetal surgery. Data are collected by the use of in-depth face-to-face
      interviews. In-depth interviews are used to understand the participant's perspectives and
      perceptions of a situation they are in. It explicitly includes participants interpretation
      and understanding of an event

      The interviews will be held in two or three moments in time (for parents opting for fetal
      surgery, there will be one additional interview, after the intervention while admitted in
      hospital): after counselling for options, but before eventual intervention; for intervention
      group shortly after the intervention, and 12 weeks after birth of the baby, or termination of
      pregnancy.
1. Background and rationale Fetal surgery is a highly technical procedure carried out by
           only a few specialised teams around the world. Fetal surgery improves outcomes for key
           conditions, but at significant procedure related fetal and maternal risk. Open
           maternal-fetal surgery is currently used on fetuses with myelomeningocele (MMC).
           Fetoscopic or minimal access fetal surgery is also being used to treat fetuses with
           congenital diaphragmatic hernia (CDH). By combining improved instrumentation, imaging,
           clinical training and public engagement The Guided Instrumentation for Fetal Therapy and
           Surgery (GIFT-Surg) project aims to provide fetal surgeons with tools to make fetal
           surgery safer and more efficient. The UZ and KU Leuven team participates in this
           engineering project.

           Following accurate diagnosis of a congenital malformation such as MMC or CDH,
           prospective parents face a range of uncertainties regarding the future of their unborn
           child, and the options provided require major ethical considerations. In the situation
           under study, termination of pregnancy may be for some parents an alternative option to
           expectant prenatal management. Fetal therapy provides a tantalising third option for
           some, where procedures are undertaken to reduce the likelihood of a more complicated
           neonatal course, potentially improving long term outcome, but at risk of amniotic fluid
           leakage, infection and most importantly very preterm delivery, associated with
           significant neonatal mortality and morbidity and long-term consequences. Balancing these
           competing risks is challenging.

             1. Myelomeningocele Prevalence, incidence, clinical presentation Myelomeningocele
                (MMC) or spina bifida is a congenital abnormality arising 28 days post-conception
                when part of the neural tube fails to close. Open spina bifida can present either
                with a flat defect without a fluid filled sac covering (myeloschisis), or
                membranous covering with extrusion of the cord into the sac (myelomeningocele). Its
                prevalence is approximately 4.9 per 10,000 live births in Europe. Myelomeningocele
                is a severe, yet non-lethal congenital abnormality affecting the central nervous
                system, with complex physical and neurodevelopmental sequelae. In most cases it is
                also associated with the Chiari Type II malformation (hindbrain herniation) and
                ventriculomegaly.

                Therapy, risks and (long-term) outcome Until recently, the only options available
                to parents, once a diagnosis was made prenatally, were expectant management with
                delivery and postnatal surgery, or a pregnancy termination. But over the last
                thirty years, it became obvious that the condition is progressive in utero, as is
                suggested by the "two-hit" hypothesis; an initial embryonic failure in neurulation
                followed by secondary changes because of continuous exposure of the spinal cord to
                the intrauterine environment and the suction gradient on the hindbrain. This led to
                the concept of fetal intervention to arrest or reverse this natural course.
                Successful fetal coverage of MMC with improved functional outcome in the lamb model
                was first described in the late 1990s. This was translated clinically with
                encouraging early results in several case series and eventually led to the
                randomized controlled Management of Myelomeningocele Study (MOMS). This study
                demonstrated that mid-gestational layered repair reduces the need for
                ventriculoperitoneal shunting, improves the degree of hindbrain herniation, and
                preserves motor function better than postnatal surgery. However, fetal surgery for
                spina bifida comes with substantial maternal and fetal risks. The fetus is at
                increased risk of premature birth and its sequelae including sepsis,
                intraventricular haemorrhage, respiratory distress syndrome, necrotizing
                enterocolitis and death. Besides there is the risk for maternal complications and
                the corporeal scar compromises uterine integrity.

             2. Congenital diaphragmatic hernia Prevalence, incidence, clinical presentation Due to
                a defect in the diaphragm during embryonic development, abdominal organs herniate
                through the defect into the thoracic cavity, interfering with lung growth,
                resulting in developmental arrest of both airways and pulmonary vasculature.
                Congenital diaphragmatic hernia (CDH) occurs in 1/2500 to 1/5000 births, depending
                on whether stillbirths are included. Although the diaphragmatic defect is
                correctable after birth, the prenatal arrest of airway and vessel development is
                the main reason for postnatal problems, leading to respiratory failure and
                pulmonary hypertension (PHT) in the neonatal period. Although prenatal referral to
                specialist centers, high throughput and advanced neonatal care has improved
                survival, still 20-30% of all cases die. Besides, survivors experience ongoing
                pulmonary and nutritional morbidity.

                Therapy, risks and (long-term) outcome In fetuses with poor prognosis, fetal lung
                growth can be stimulated by fetoscopic endoluminal tracheal occlusion (FETO) with a
                balloon. The fetal lung is a net secretor of fluid into the amniotic cavity and the
                lungs are maintained at a small positive pressure in normal development. Fetal
                tracheal occlusion (TO) prevents egress of lung liquid, leading to increased back
                pressure, in turn promoting stretch-induced growth of airways and vessels. TO
                appears to trigger sufficient lung growth to protect the lung from developing
                pulmonary hypoplasia. In utero reversal of the occlusion prompts pulmonary
                maturation. Experimentally an endoscopic technique of tracheal occlusion using a
                balloon was developed. In 2004, it was first applied clinically and referred to as
                Fetoscopic Endoluminal Tracheal Occlusion (FETO).

                The major risk following the procedure is spontaneous pre-labour rupture of
                membranes before 37 weeks (PPROM). Gestational age at delivery logically is an
                important predictor of survival and morbidity in CDH fetuses, also when undergoing
                fetal therapy.

                A meta-analysis suggests that FETO improves survival, but the procedure remains to
                be considered investigational and is therefore currently evaluated within a
                randomized controlled clinical trial (www.totaltrial.eu).

             3. Acceptability For an intervention to be effective it also needs to be acceptable to
                women and their families. "Acceptability" can be defined as a multi-faceted
                construct that reflects the extent to which people delivering or receiving a
                healthcare intervention consider it to be appropriate, based on anticipated or
                experienced cognitive and emotional responses to the intervention. Based on this
                definition a theoretical framework of acceptability comprising seven components has
                been developed: affective attitude, burden, perceived effectiveness, ethicality,
                intervention coherence, opportunity costs, and self-efficacy. Successful
                implementation of an intervention means that it is acceptable for both recipients
                and deliverers. This study focuses on the recipients; measurement of acceptability
                for deliverers will be considered as other facets of the wider GIFT-Surg project.

           Timing is an important factor in the assessment as the relationship to perceived and
           actual experiences may differ. Acceptability is therefore assessed in two or three
           moments in time: prospective acceptability, concurrent acceptability and retrospective
           acceptability.

        2. Trial objectives

           Primary objective: to assess how women (and their partners) perceive the acceptability
           of a fetal surgical intervention for MMC and CDH. Participants will be asked to share
           their thoughts, views, feelings and experiences with regards to the decision to
           participate in fetal surgery.

        3. Trial Design

           This is a qualitative in-depth interview study, to include approximately 48
           women/couples at University Hospital Leuven for two fetal conditions (MMC and CDH),
           given all data on these 48 patients are complete. An estimated dropout rate of 50% means
           that in total 4 patients per treatment option (fetal surgery, expectant management,
           termination), and per condition (MMC or CDH) will be available for analysis.

           As not all parents opt for fetal surgery, after referral and counselling for prenatal
           diagnosed isolated spinal defects and congenital diaphragmatic hernia, patients fall
           into three groups: 1. Parents opting for fetal surgery, 2. Parents opting for
           termination of pregnancy and 3. Parents opting for expectant management. To assess
           acceptability of the intervention, it is of value to assess acceptability of the
           intervention in all three groups. In particular, knowledge of non-acceptability
           important.

        4. Trial Intervention

           Data collection will take place by executing face-to-face interviews. The interviews
           will be held in three moments in time: before, during (i.e. shortly after the
           intervention) and after the intervention. Prospective acceptability will be assessed,
           after patients have been first counselled and assessed, but before the intervention at
           stake. Concurrent acceptability, patients will be interviewed shortly after the
           intervention while still admitted for post-surgery observation, and retrospective
           acceptability three months after delivery.

           The interviews assessing prospective and concurrent acceptability will always be planned
           along visits to the treatment hospital so parents never have to come on purpose to the
           hospital for an interview, and will be held in Dutch or English. The interviews are
           expected to last approximately 30-60 minutes and will follow an interview guide. As it
           is acknowledged women (and their partners) go through an intensive and emotionally
           upsetting process, interviews will only be carried out if the patient is capable of
           participating in an interview, based on the patient's personal assessment as well as
           their doctor's assessment. For retrospective acceptability, depending on participant's
           preference, the interview can take place through teleconference or phone.

           Data-collection Data are collected by the use of in-depth interviews. In-depth
           interviews are used to understand the participant's perspectives and perceptions of a
           situation they are in. It explicitly includes participants interpretation and
           understanding of an event. The style of interviewing will be 'responsive'; this style
           emphasises on the importance of building a relationship of trust between interviewer and
           interviewee. This is done by creating a quiet and calm environment, an empathically
           neutral position of the interviewer and an open approach by using verbal and non-verbal
           communication. There will not be a set list of questions, but an interview guide based
           on one main-question, with different themes for probing, based on the seven components
           of the framework of acceptability. The interview will follow six stages as described by
           Yeo et al.: arrival and introduction: establish rapport, 'host' the interaction(stage
           1); introducing the research (aims and objectives, confidentiality, voluntary, scope of
           interview (participant in control), no right or wrong answers(stage 2); beginning of the
           interview: discuss contextual background information for reference and set the tone
           (stage 3); during the interview (start recording: breadth and depth of subject)(stage
           4); ending the interview: advance notice of end and opportunity for respondent to raise
           anything important not yet discussed (stage 5); and after the interview: thanking and
           emphasize on value of sharing their experience, how information is treated and used,
           follow up and further meetings to be scheduled (stage 6)(interview guide).

           The interviews will be recorded digitally with an audio recorder. Subsequently,
           interviews will be transcribed and coded transcripts will be translated into English and
           used for analysis. Back-translation will be used for a sample of 5 transcripts in Dutch
           to ensure accuracy.

        5. Sample size

           Intended sample size in Belgium is 12 women for MMC and 12 for CDH at study completion;
           in the UK the investigators expect to include 10 women for MMC and 5 for CDH. This
           sample size has been determined from interviewing clinical stakeholders. Sample size in
           qualitative research are usually small, as in analysis there will be at some point a
           moment in which no new information is obtained from additional interviews. This is also
           called saturation. The aim of this research is not to determine statistically
           significant discriminatory variables, but to get an in-depth understanding of the views
           and preferences of the participants, and to assess acceptability of the intervention.
           Exact sample size will depend on saturation

        6. Analysis

      The analysis is purely qualitative. The interviews will be transcribed verbatim by the
      researcher. Content analyses will be performed by using the qualitative software programme.
      First, initial content and subjects of interest are identified, the so-called familiarization
      with the data. This first step is followed by the initial construct of a framework. The
      framework constructs the headings under which respondent's views, feelings, experiences and
      perceptions can be organized. The framework is than used for labelling the data: quotes or
      pieces of text are ordered according to the different themes to fit in. The next step will be
      further refinement of the framework by making connections between categories and placing them
      in a broader context related to the framework of acceptability. To improve the quality of the
      analysis, at various moments interim analyses will be discussed among co-authors with a
      background in psychology and qualitative analysis. Thereafter, all previously analyzed
      transcripts will be reviewed to check that the content is consistent with this concept
      (thematic analysis).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: Prospective acceptability of fetal surgery in the context of Myelomeningocele and Congenital Diaphragmatic Hernia.
time frame: After evaluation and counseling, if applicable, before undergoing fetal surgery.
description: Qualitative methodology. Prospective acceptability, as perceived by prospective parents eligible for fetal surgery, assessed by in-depth face-to face interviews.
measure: Concurrent acceptability of fetal surgery in the context of Myelomeningocele and Congenital Diaphragmatic Hernia.
time frame: After fetal surgery, within 7 days after surgery.
description: Qualitative methodology. Concurrent acceptability, as perceived by prospective parents eligible for fetal surgery, assessed by in-depth face-to face interviews.
measure: Retrospective acceptability of fetal surgery in the context of Myelomeningocele and Congenital Diaphragmatic Hernia.
time frame: Three months after birth of the baby, or three months after termination of the pregnancy.
description: Qualitative methodology. Retrospective acceptability, as perceived by prospective parents eligible for fetal surgery, assessed by in-depth face-to face interviews.
arm group label: Parents eligible for fetal surgery
arm group type: Other
description: Parents eligible for fetal surgery will undergo two or three in-depth face-tot-face interviews, to determine their perception of acceptability of fetal surgery.
intervention type: Other
intervention name: In-depth interview
description: The 'intervention' administered to this group of participants are two or three in-depth interviews (average 30-60 m minutes per interview) on their experiences, views, feelings and thoughts (perceptions) regarding acceptability of the fetal surgery.
arm group label: Parents eligible for fetal surgery
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Jan Deprest, Professor
role: Principal Investigator
affiliation: Universitaire Ziekenhuizen KU Leuven
last name: Neil Marlow
role: Principal Investigator
affiliation: University College London Hospital
last name: Jan Deprest, Professor
phone: +3216 34 42 11
phone ext: 44211
email: jan.deprest@uzleuven.be
last name: Neeltje Crombag, Dr
phone: +3216 34 52 22
phone ext: 45222
email: neeltje.crombag@kuleuven.be
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
contact backup: 
country: Belgium
country: United Kingdom
citation: Cohen AR, Couto J, Cummings JJ, Johnson A, Joseph G, Kaufman BA, Litman RS, Menard MK, Moldenhauer JS, Pringle KC, Schwartz MZ, Walker WO Jr, Warf BC, Wax JR; MMC Maternal-Fetal Management Task Force. Position statement on fetal myelomeningocele repair. Am J Obstet Gynecol. 2014 Feb;210(2):107-11. doi: 10.1016/j.ajog.2013.09.016. Epub 2013 Sep 18.
PMID: 24055581
citation: Deprest J, Nicolaides K, Done' E, Lewi P, Barki G, Largen E, DeKoninck P, Sandaite I, Ville Y, Benachi A, Jani J, Amat-Roldan I, Gratacos E. Technical aspects of fetal endoscopic tracheal occlusion for congenital diaphragmatic hernia. J Pediatr Surg. 2011 Jan;46(1):22-32. doi: 10.1016/j.jpedsurg.2010.10.008.
PMID: 21238635
citation: Ville Y. Fetal therapy: practical ethical considerations. Prenat Diagn. 2011 Jul;31(7):621-7. doi: 10.1002/pd.2808. Epub 2011 Jun 10.
PMID: 21660998
citation: Adzick NS, Thom EA, Spong CY, Brock JW 3rd, Burrows PK, Johnson MP, Howell LJ, Farrell JA, Dabrowiak ME, Sutton LN, Gupta N, Tulipan NB, D'Alton ME, Farmer DL; MOMS Investigators. A randomized trial of prenatal versus postnatal repair of myelomeningocele. N Engl J Med. 2011 Mar 17;364(11):993-1004. doi: 10.1056/NEJMoa1014379. Epub 2011 Feb 9.
PMID: 21306277
citation: Al-Maary J, Eastwood MP, Russo FM, Deprest JA, Keijzer R. Fetal Tracheal Occlusion for Severe Pulmonary Hypoplasia in Isolated Congenital Diaphragmatic Hernia: A Systematic Review and Meta-analysis of Survival. Ann Surg. 2016 Dec;264(6):929-933. doi: 10.1097/SLA.0000000000001675.
PMID: 26910202
citation: Sekhon M, Cartwright M, Francis JJ. Acceptability of healthcare interventions: an overview of reviews and development of a theoretical framework. BMC Health Serv Res. 2017 Jan 26;17(1):88. doi: 10.1186/s12913-017-2031-8.
PMID: 28126032
citation: Farmer DL, Thom EA, Brock JW 3rd, Burrows PK, Johnson MP, Howell LJ, Farrell JA, Gupta N, Adzick NS; Management of Myelomeningocele Study Investigators. The Management of Myelomeningocele Study: full cohort 30-month pediatric outcomes. Am J Obstet Gynecol. 2018 Feb;218(2):256.e1-256.e13. doi: 10.1016/j.ajog.2017.12.001. Epub 2017 Dec 12.
PMID: 29246577
citation: Johnson MP, Bennett KA, Rand L, Burrows PK, Thom EA, Howell LJ, Farrell JA, Dabrowiak ME, Brock JW 3rd, Farmer DL, Adzick NS; Management of Myelomeningocele Study Investigators. The Management of Myelomeningocele Study: obstetrical outcomes and risk factors for obstetrical complications following prenatal surgery. Am J Obstet Gynecol. 2016 Dec;215(6):778.e1-778.e9. doi: 10.1016/j.ajog.2016.07.052. Epub 2016 Aug 2.
PMID: 27496687
responsible party type: Sponsor
mesh term: Meningomyelocele
mesh term: Spina Bifida Cystica
mesh term: Hernias, Diaphragmatic, Congenital
mesh term: Hernia, Diaphragmatic
sharing ipd: Undecided