<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/NCT04432168</url>
  </required_header>
  <id_info>
    <org_study_id>NL6442700018</org_study_id>
    <nct_id>NCT04432168</nct_id>
  </id_info>
  <brief_title>The TAPS Trial - Fetoscopic Laser Surgery for Twin Anemia Polycythemia Sequence</brief_title>
  <official_title>The TAPS Trial - Fetoscopic Laser Surgery for Twin Anemia-Polycythemia Sequence - a Multicenter Open-Label Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Leiden University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Leiden University Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</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 multicenter open-label randomized controlled trial is set up to evaluate the effect of&#xD;
      fetoscopic laser surgery on the gestational age at birth for monochorionic twin pregnancies&#xD;
      diagnosed with twin anemia-polycythemia sequence. Half op the patients will be treated with&#xD;
      fetoscopic laser surgery, while the other half will be managed with standard treatment. The&#xD;
      hypothesis is that fetoscopic laser therapy will improve neonatal outcome by prolonging&#xD;
      pregnancy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Rationale: Monochorionic twins share one placenta and are connected to each other via&#xD;
      vascular anastomoses at the placental surface, allowing the blood to transfer&#xD;
      bi-directionally between the two fetuses. Unbalanced inter-twin blood transfusion can result&#xD;
      in twin anemia-polycythemia sequence (TAPS). Management options include: fetoscopic laser&#xD;
      surgery, intrauterine blood transfusion (IUT) with or without partial exchange transfusion&#xD;
      (PET), preterm delivery, selective feticide and expectant management. The optimal treatment&#xD;
      for TAPS is not clear. Fetoscopic laser surgery is the only causative treatment option, but&#xD;
      data on the feasibility of this procedure are mainly based on case reports and small cohort&#xD;
      studies. A large randomized controlled trial is needed to evaluate the possible beneficial&#xD;
      effect of fetoscopic laser surgery and to determine the optimal treatment option for TAPS.&#xD;
&#xD;
      Objective: The aim of this trial is to investigate whether fetoscopic laser surgery improves&#xD;
      the outcome for TAPS twins as compared to the control group (standard care consisting of&#xD;
      expectant management, IUT, preterm delivery). The hypothesis is that fetoscopic laser therapy&#xD;
      will improve neonatal outcome by prolonging pregnancy.&#xD;
&#xD;
      Study design: International multi-centered open-label randomized controlled trial to assess&#xD;
      whether fetoscopic laser surgery (experimental group) improves the outcome of TAPS twins&#xD;
      compared to standard care (control group).&#xD;
&#xD;
      Study population: Monochorionic twin pregnancies with TAPS stage ≥ 2 (spontaneous or&#xD;
      post-laser) diagnosed between 20 and 28 weeks of gestation.&#xD;
&#xD;
      Intervention: In the experimental group fetoscopic laser surgery is performed, whereas the&#xD;
      control group is treated with standard care (expectant management, IUT (with PET), selective&#xD;
      feticide and/or preterm delivery, depending on the opinion of the fetal surgeon).&#xD;
&#xD;
      Main study endpoints: The primary outcome is gestational age at birth. Secondary outcomes&#xD;
      include: perinatal mortality or severe neonatal morbidity, hematological complication,&#xD;
      procedure related complications and long-term neurodevelopmental outcome at 2 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 30, 2019</start_date>
  <completion_date type="Anticipated">April 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">April 30, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Gestational Age at Birth</measure>
    <time_frame>2 weeks after expected date of birth</time_frame>
    <description>Gestational age: completed weeks + additional days since the first day of the last menstruational period of the mother.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of patients with perinatal mortality</measure>
    <time_frame>42 days (28 days neonatal period+2 weeks postdates) after expected date of birth</time_frame>
    <description>Perinatal mortality is defined as fetal death or neonatal death (demise of a liveborn child within 28 days after birth)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with severe neonatal morbidity</measure>
    <time_frame>42 days (28 days neonatal period+2 weeks postdates) after expected date of birth</time_frame>
    <description>Severe neonatal morbidity is defined as the presence of at least one of the following:&#xD;
Respiratory distress syndrome requiring surfactant or mechanical ventilation&#xD;
Proven early onset neonatal sepsis with positive blood cultures within 72 hours postpartum&#xD;
Retinopathy of prematurity stage 3 or higher&#xD;
Necrotizing enterocolitis stage 2 or higher&#xD;
Patent ductus arteriosus requiring medical therapy or surgical closure&#xD;
Severe cerebral injury (defined as intraventricular hemorrhage grade 3 or higher, cystic periventricular leukomalacia grade 2 or higher, ventricular dilatation greater than the 97th centile, porencephalic or parenchymal cysts or other severe cerebral lesions)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with hematological complications</measure>
    <time_frame>2 weeks after expected date of birth</time_frame>
    <description>Hematological complications are defined as the presence of at least one of the following:&#xD;
Anemia in donor requiring a blood transfusion within 24 hours after birth&#xD;
Polycythemia in recipient requiring a partial exchange transfusion within 24 hours after birth&#xD;
necrotic skin injury&#xD;
limb ischemia&#xD;
platelet count &lt; 150,000/microL&#xD;
albumin levels &lt; 20 g/L&#xD;
protein levels &lt; 40 g/L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with procedure-related complications</measure>
    <time_frame>2 weeks after expected date of birth</time_frame>
    <description>Procedure-related complications are defined as at least one of the following:&#xD;
amniotic band syndrome&#xD;
iatrogenic monoamnionicity&#xD;
Preterm premature rupture of the membranes&#xD;
Placental abruption&#xD;
clinical chorioamnionitis&#xD;
histological chorioamnionitis and/or funisitis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patient with mild neurodevelopmental impairment</measure>
    <time_frame>2 years after expected date of birth</time_frame>
    <description>Mild neurodevelopmental impairment is defined as at least one of the following:&#xD;
cerebral palsy (spastic bilateral, spastic unilateral, or mixed)&#xD;
Impaired cognitive or motor development defined as Score &lt; 85 (1 standard deviation (SD) below the mean) as assessed by Bayley Scales of Infant and Toddler Development version 3 (BSID-III)&#xD;
Impaired functioning in communication, fine and gross motor, problem solving, personal and social functioning defined as Score &gt; 1 SD below the mean as assessed by Ages and Stages Questionnaire version 3 (ASQ-III)&#xD;
severe visual loss (blind or partially sighted)&#xD;
severe hearing loss (needing hearing aids)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with severe neurodevelopmental impairment</measure>
    <time_frame>2 years after expected date of birth</time_frame>
    <description>Severe neurodevelopmental impairment is defined as at least one of the following:&#xD;
cerebral palsy defined as a gross motor function classification system (CMFCS) grade &gt; 1&#xD;
Impaired cognitive or motor development defined as a score &lt; 70 (2 SD below the mean) as assessed by the Bayley Scales of Infant and Toddler Development version 3 (BSID-III)&#xD;
Impaired functioning in communication, fine and gross motor, problem solving, personal and social functioning defined as a score &gt; 2 SD below the mean as assessed by Ages and Stages Questionnaire version 3 (ASQ-III)&#xD;
Bilateral blindness defined as visual acuity of less than 3/60 in the better eye&#xD;
Bilateral deafness defined as severe or profound hearing loss in both ears (severe hearing loss: a person can only hear sounds &gt; 70-89 decibel , profound hearing loss: a person can only hear sounds &gt; 90 decibel</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with behavioral problems</measure>
    <time_frame>2 years after expected date of birth</time_frame>
    <description>Behavioral problems are defined as a T-score ≥ 64 for one of the following broad band scales: total problem score, Internalizing problems (anxious/depressed, withdrawn, somatic complaints), Externalizing problems (rule-breaking, aggressive behavior) as measured with the Child Behaviour Checklist 1.5-5 years</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">44</enrollment>
  <condition>Twin Anemia Polycythemia Sequence</condition>
  <arm_group>
    <arm_group_label>Fetoscopic Laser Surgery</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>fetoscopic laser coagulation of the vascular anastomoses at the placental surface</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard Treatment</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Expectant management, IUT (with or without PET), preterm delivery</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Fetoscopic Laser Surgery</intervention_name>
    <description>Fetoscopic Photocoagulation of the connecting vascular anastomoses on the surface of the placenta.</description>
    <arm_group_label>Fetoscopic Laser Surgery</arm_group_label>
    <other_name>Fetoscopic Laser Coagulation</other_name>
    <other_name>Laser therapy</other_name>
    <other_name>Fetoscopic Laser Ablation</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Standard Treatment</intervention_name>
    <description>In the control group, the choices of treatment include expectant management, intrauterine transfusion (IUT) (with or without partial exchange transfusion (PET)) or preterm delivery, depending on the judgment of the fetal surgeon with regard to the gestational age and state of the disease.&#xD;
Expectant management will consist of close monitoring with ultrasound including Doppler measurements of the middle cerebral artery peak systolic velocity (MCA-PSV), at least every week.&#xD;
IUT: the intrauterine infusion of red blood cells into the circulation of the donor twin treat anemia.&#xD;
PET: the intrauterine infusion of saline into the circulation of the recipient twin to treat polycythemia.&#xD;
Preterm delivery: Induction of labor or cesarean section before 36 weeks of gestation.</description>
    <arm_group_label>Standard Treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Monochorionic twin pregnancy complicated by either spontaneous or post-laser twin&#xD;
             anemia polycythemia sequence (TAPS), stage ≥ 2, diagnosed between 20+0 and till 28+0&#xD;
             weeks of gestation&#xD;
&#xD;
          -  Women aged 18 years or more, who are able to consent.&#xD;
&#xD;
          -  Written informed consent to participate in this randomized controlled trial, forms&#xD;
             being approved by the Ethical Committees.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  TAPS stage 1&#xD;
&#xD;
          -  TAPS stage≥ 2, diagnosed within 1 week after laser surgery for twin-twin transfusion&#xD;
             syndrome (TTTS) (a large inter-twin middle cerebral artery peak systolic velocity&#xD;
             difference within a week after laser for TTTS is likely to related to hemodynamic&#xD;
             reequilibration, and is usually not based on TAPS)&#xD;
&#xD;
          -  Triplet pregnancies, or higher order multiple pregnancies&#xD;
&#xD;
          -  TAPS cases that already underwent an intrauterine treatment (with the exception of&#xD;
             laser surgery for TTTS in post-laser TAPS cases)&#xD;
&#xD;
          -  Congenital abnormalities (including severe cerebral injury) in one or both twins&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dick Oepkes, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Leiden University Medical Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Femke Slaghekke, MD PhD</last_name>
    <phone>+31 71 52 97211</phone>
    <email>f.slaghekke@lumc.nl</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Lisanne Tollenaar, BSc</last_name>
    <phone>+31653413875</phone>
    <email>l.s.a.tollenaar@lumc.nl</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Yale University</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>208327</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Ozan Bahtiyar, MD PhD</last_name>
    </contact>
    <investigator>
      <last_name>Ozan Bahtiyar, MD PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Vittore Buzzi Children's Hospital</name>
      <address>
        <city>Milan</city>
        <state>Lombardy</state>
        <zip>20154</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mariano Lanna, MD PhD</last_name>
      <email>info@terapiafetale.it</email>
    </contact>
    <investigator>
      <last_name>Mariano Lanna, MD PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Leiden University Medical Center</name>
      <address>
        <city>Leiden</city>
        <state>South-Holland</state>
        <zip>2333ZA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dick Oepkes, MD PhD</last_name>
      <phone>+31715261688</phone>
      <email>d.oepkes@lumc.nl</email>
    </contact>
    <contact_backup>
      <last_name>Femke Slaghekke, MD PhD</last_name>
      <phone>+31715297211</phone>
      <email>f.slaghekke@lumc.nl</email>
    </contact_backup>
    <investigator>
      <last_name>Dick Oepkes, MD PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Enrico Lopriore, MD PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Femke Slaghekke, MD PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Lisanne Tollenaar, BSc</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Vall d'Hebron University Hospital</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Carlota Rodo, MD PhD</last_name>
      <email>crodo@vhebron.net</email>
    </contact>
    <contact_backup>
      <last_name>Silivia Arevalo, MD PhD</last_name>
      <email>siareval@vhebron.net</email>
    </contact_backup>
    <investigator>
      <last_name>Carlota Rodo, MD PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Silivia Arevalo, MD PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Pablo Garcia-Manau, MD PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Karolinska University Hospital</name>
      <address>
        <city>Stockholm</city>
        <state>Södermanland</state>
        <zip>141 86</zip>
        <country>Sweden</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Lotta Herling, MD PhD</last_name>
      <email>lotta.herling@sll.se</email>
    </contact>
    <investigator>
      <last_name>Lotta Herling, MD PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Italy</country>
    <country>Netherlands</country>
    <country>Spain</country>
    <country>Sweden</country>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Lopriore E, Middeldorp JM, Oepkes D, Kanhai HH, Walther FJ, Vandenbussche FP. Twin anemia-polycythemia sequence in two monochorionic twin pairs without oligo-polyhydramnios sequence. Placenta. 2007 Jan;28(1):47-51. doi: 10.1016/j.placenta.2006.01.010. Epub 2006 Mar 3.</citation>
    <PMID>16516289</PMID>
  </reference>
  <reference>
    <citation>Robyr R, Lewi L, Salomon LJ, Yamamoto M, Bernard JP, Deprest J, Ville Y. Prevalence and management of late fetal complications following successful selective laser coagulation of chorionic plate anastomoses in twin-to-twin transfusion syndrome. Am J Obstet Gynecol. 2006 Mar;194(3):796-803. doi: 10.1016/j.ajog.2005.08.069.</citation>
    <PMID>16522415</PMID>
  </reference>
  <reference>
    <citation>Sananes N, Veujoz M, Severac F, Barthoulot M, Meyer N, Weingertner AS, Kohler M, Guerra F, Gaudineau A, Nisand I, Favre R. Evaluation of the Utility of in utero Treatment of Twin Anemia-Polycythemia Sequence. Fetal Diagn Ther. 2015;38(3):170-8. doi: 10.1159/000380822. Epub 2015 Mar 17.</citation>
    <PMID>25790745</PMID>
  </reference>
  <reference>
    <citation>Slaghekke F, Favre R, Peeters SH, Middeldorp JM, Weingertner AS, van Zwet EW, Klumper FJ, Oepkes D, Lopriore E. Laser surgery as a management option for twin anemia-polycythemia sequence. Ultrasound Obstet Gynecol. 2014 Sep;44(3):304-10. doi: 10.1002/uog.13382. Epub 2014 Aug 4.</citation>
    <PMID>24706478</PMID>
  </reference>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>May 11, 2020</study_first_submitted>
  <study_first_submitted_qc>June 11, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 16, 2020</study_first_posted>
  <last_update_submitted>June 11, 2020</last_update_submitted>
  <last_update_submitted_qc>June 11, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 16, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Leiden University Medical Center</investigator_affiliation>
    <investigator_full_name>DickOepkes</investigator_full_name>
    <investigator_title>Prof. dr. D. Oepkes</investigator_title>
  </responsible_party>
  <keyword>Monochorionic Twins</keyword>
  <keyword>Twin-Twin Transfusion Syndrome</keyword>
  <keyword>Fetoscopic Laser Surgery</keyword>
  <keyword>Intrauterine Transfusion</keyword>
  <keyword>Partial Exchange Transfusion</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anemia</mesh_term>
    <mesh_term>Polycythemia</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/NCT04432168
org study id: NL6442700018
nct id: NCT04432168
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This multicenter open-label randomized controlled trial is set up to evaluate the effect of
      fetoscopic laser surgery on the gestational age at birth for monochorionic twin pregnancies
      diagnosed with twin anemia-polycythemia sequence. Half op the patients will be treated with
      fetoscopic laser surgery, while the other half will be managed with standard treatment. The
      hypothesis is that fetoscopic laser therapy will improve neonatal outcome by prolonging
      pregnancy.
Rationale: Monochorionic twins share one placenta and are connected to each other via
      vascular anastomoses at the placental surface, allowing the blood to transfer
      bi-directionally between the two fetuses. Unbalanced inter-twin blood transfusion can result
      in twin anemia-polycythemia sequence (TAPS). Management options include: fetoscopic laser
      surgery, intrauterine blood transfusion (IUT) with or without partial exchange transfusion
      (PET), preterm delivery, selective feticide and expectant management. The optimal treatment
      for TAPS is not clear. Fetoscopic laser surgery is the only causative treatment option, but
      data on the feasibility of this procedure are mainly based on case reports and small cohort
      studies. A large randomized controlled trial is needed to evaluate the possible beneficial
      effect of fetoscopic laser surgery and to determine the optimal treatment option for TAPS.

      Objective: The aim of this trial is to investigate whether fetoscopic laser surgery improves
      the outcome for TAPS twins as compared to the control group (standard care consisting of
      expectant management, IUT, preterm delivery). The hypothesis is that fetoscopic laser therapy
      will improve neonatal outcome by prolonging pregnancy.

      Study design: International multi-centered open-label randomized controlled trial to assess
      whether fetoscopic laser surgery (experimental group) improves the outcome of TAPS twins
      compared to standard care (control group).

      Study population: Monochorionic twin pregnancies with TAPS stage ≥ 2 (spontaneous or
      post-laser) diagnosed between 20 and 28 weeks of gestation.

      Intervention: In the experimental group fetoscopic laser surgery is performed, whereas the
      control group is treated with standard care (expectant management, IUT (with PET), selective
      feticide and/or preterm delivery, depending on the opinion of the fetal surgeon).

      Main study endpoints: The primary outcome is gestational age at birth. Secondary outcomes
      include: perinatal mortality or severe neonatal morbidity, hematological complication,
      procedure related complications and long-term neurodevelopmental outcome at 2 years.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Gestational Age at Birth
time frame: 2 weeks after expected date of birth
description: Gestational age: completed weeks + additional days since the first day of the last menstruational period of the mother.
measure: Number of patients with perinatal mortality
time frame: 42 days (28 days neonatal period+2 weeks postdates) after expected date of birth
description: Perinatal mortality is defined as fetal death or neonatal death (demise of a liveborn child within 28 days after birth)
measure: Number of patients with severe neonatal morbidity
time frame: 42 days (28 days neonatal period+2 weeks postdates) after expected date of birth
description: Severe neonatal morbidity is defined as the presence of at least one of the following:
Respiratory distress syndrome requiring surfactant or mechanical ventilation
Proven early onset neonatal sepsis with positive blood cultures within 72 hours postpartum
Retinopathy of prematurity stage 3 or higher
Necrotizing enterocolitis stage 2 or higher
Patent ductus arteriosus requiring medical therapy or surgical closure
Severe cerebral injury (defined as intraventricular hemorrhage grade 3 or higher, cystic periventricular leukomalacia grade 2 or higher, ventricular dilatation greater than the 97th centile, porencephalic or parenchymal cysts or other severe cerebral lesions)
measure: Number of patients with hematological complications
time frame: 2 weeks after expected date of birth
description: Hematological complications are defined as the presence of at least one of the following:
Anemia in donor requiring a blood transfusion within 24 hours after birth
Polycythemia in recipient requiring a partial exchange transfusion within 24 hours after birth
necrotic skin injury
limb ischemia
platelet count < 150,000/microL
albumin levels < 20 g/L
protein levels < 40 g/L
measure: Number of patients with procedure-related complications
time frame: 2 weeks after expected date of birth
description: Procedure-related complications are defined as at least one of the following:
amniotic band syndrome
iatrogenic monoamnionicity
Preterm premature rupture of the membranes
Placental abruption
clinical chorioamnionitis
histological chorioamnionitis and/or funisitis
measure: Number of patient with mild neurodevelopmental impairment
time frame: 2 years after expected date of birth
description: Mild neurodevelopmental impairment is defined as at least one of the following:
cerebral palsy (spastic bilateral, spastic unilateral, or mixed)
Impaired cognitive or motor development defined as Score < 85 (1 standard deviation (SD) below the mean) as assessed by Bayley Scales of Infant and Toddler Development version 3 (BSID-III)
Impaired functioning in communication, fine and gross motor, problem solving, personal and social functioning defined as Score > 1 SD below the mean as assessed by Ages and Stages Questionnaire version 3 (ASQ-III)
severe visual loss (blind or partially sighted)
severe hearing loss (needing hearing aids)
measure: Number of patients with severe neurodevelopmental impairment
time frame: 2 years after expected date of birth
description: Severe neurodevelopmental impairment is defined as at least one of the following:
cerebral palsy defined as a gross motor function classification system (CMFCS) grade > 1
Impaired cognitive or motor development defined as a score < 70 (2 SD below the mean) as assessed by the Bayley Scales of Infant and Toddler Development version 3 (BSID-III)
Impaired functioning in communication, fine and gross motor, problem solving, personal and social functioning defined as a score > 2 SD below the mean as assessed by Ages and Stages Questionnaire version 3 (ASQ-III)
Bilateral blindness defined as visual acuity of less than 3/60 in the better eye
Bilateral deafness defined as severe or profound hearing loss in both ears (severe hearing loss: a person can only hear sounds > 70-89 decibel , profound hearing loss: a person can only hear sounds > 90 decibel
measure: Number of patients with behavioral problems
time frame: 2 years after expected date of birth
description: Behavioral problems are defined as a T-score ≥ 64 for one of the following broad band scales: total problem score, Internalizing problems (anxious/depressed, withdrawn, somatic complaints), Externalizing problems (rule-breaking, aggressive behavior) as measured with the Child Behaviour Checklist 1.5-5 years
arm group label: Fetoscopic Laser Surgery
arm group type: Experimental
description: fetoscopic laser coagulation of the vascular anastomoses at the placental surface
arm group label: Standard Treatment
arm group type: Other
description: Expectant management, IUT (with or without PET), preterm delivery
intervention type: Procedure
intervention name: Fetoscopic Laser Surgery
description: Fetoscopic Photocoagulation of the connecting vascular anastomoses on the surface of the placenta.
arm group label: Fetoscopic Laser Surgery
other name: Fetoscopic Laser Coagulation
other name: Laser therapy
other name: Fetoscopic Laser Ablation
intervention type: Other
intervention name: Standard Treatment
description: In the control group, the choices of treatment include expectant management, intrauterine transfusion (IUT) (with or without partial exchange transfusion (PET)) or preterm delivery, depending on the judgment of the fetal surgeon with regard to the gestational age and state of the disease.
Expectant management will consist of close monitoring with ultrasound including Doppler measurements of the middle cerebral artery peak systolic velocity (MCA-PSV), at least every week.
IUT: the intrauterine infusion of red blood cells into the circulation of the donor twin treat anemia.
PET: the intrauterine infusion of saline into the circulation of the recipient twin to treat polycythemia.
Preterm delivery: Induction of labor or cesarean section before 36 weeks of gestation.
arm group label: Standard Treatment
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: No
last name: Dick Oepkes, MD PhD
role: Principal Investigator
affiliation: Leiden University Medical Center
last name: Femke Slaghekke, MD PhD
phone: +31 71 52 97211
email: f.slaghekke@lumc.nl
last name: Lisanne Tollenaar, BSc
phone: +31653413875
email: l.s.a.tollenaar@lumc.nl
facility: 
status: Not yet recruiting
contact: 
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facility: 
status: Recruiting
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facility: 
status: Recruiting
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investigator: 
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facility: 
status: Recruiting
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status: Not yet recruiting
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country: Italy
country: Netherlands
country: Spain
country: Sweden
country: United States
citation: Lopriore E, Middeldorp JM, Oepkes D, Kanhai HH, Walther FJ, Vandenbussche FP. Twin anemia-polycythemia sequence in two monochorionic twin pairs without oligo-polyhydramnios sequence. Placenta. 2007 Jan;28(1):47-51. doi: 10.1016/j.placenta.2006.01.010. Epub 2006 Mar 3.
PMID: 16516289
citation: Robyr R, Lewi L, Salomon LJ, Yamamoto M, Bernard JP, Deprest J, Ville Y. Prevalence and management of late fetal complications following successful selective laser coagulation of chorionic plate anastomoses in twin-to-twin transfusion syndrome. Am J Obstet Gynecol. 2006 Mar;194(3):796-803. doi: 10.1016/j.ajog.2005.08.069.
PMID: 16522415
citation: Sananes N, Veujoz M, Severac F, Barthoulot M, Meyer N, Weingertner AS, Kohler M, Guerra F, Gaudineau A, Nisand I, Favre R. Evaluation of the Utility of in utero Treatment of Twin Anemia-Polycythemia Sequence. Fetal Diagn Ther. 2015;38(3):170-8. doi: 10.1159/000380822. Epub 2015 Mar 17.
PMID: 25790745
citation: Slaghekke F, Favre R, Peeters SH, Middeldorp JM, Weingertner AS, van Zwet EW, Klumper FJ, Oepkes D, Lopriore E. Laser surgery as a management option for twin anemia-polycythemia sequence. Ultrasound Obstet Gynecol. 2014 Sep;44(3):304-10. doi: 10.1002/uog.13382. Epub 2014 Aug 4.
PMID: 24706478
responsible party type: Principal Investigator
investigator affiliation: Leiden University Medical Center
investigator full name: DickOepkes
investigator title: Prof. dr. D. Oepkes
mesh term: Anemia
mesh term: Polycythemia
sharing ipd: No