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TRAP Intervention STudy: Early Versus Late Intervention for Twin Reversed Arterial Perfusion Sequence (TRAPIST)

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ClinicalTrials.gov Identifier: NCT02621645
Recruitment Status : Recruiting
First Posted : December 3, 2015
Last Update Posted : September 21, 2017
Sponsor:
Collaborators:
St. George's Hospital, University of London (UK sponsor)
Leiden University Medical Center
Ospedalo Maggiore Policlinico di Milano, Italy
Hospital Universitari Vall d'hebron Barcelona, Spain
Centro Médico-Chirurgical et Obstétrical (CMCO) Schiltigheim, France
Universitätsklinik für Frauenheilkunde und Geburtshilfe Graz, Austria
Ospedale dei Bambini "Vittore Buzzi" Milano, Italy
Birmingham Women's Hospital, UK
Sheba Medical Center Tel-Hashomer, Israel
Children's Memorial Hermann Hospital Houston Texas, USA
Universitätsklinikum Hamburg-Eppendorf, Germany
Mount Sinai Hospital, Canada
University of Pittsburgh
University Hospital Innsbruck, Austria
Spedali Civili, University of Brescia, Italy
Information provided by (Responsible Party):
Universitaire Ziekenhuizen Leuven

Tracking Information
First Submitted Date  ICMJE November 12, 2015
First Posted Date  ICMJE December 3, 2015
Last Update Posted Date September 21, 2017
Study Start Date  ICMJE May 2016
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 2, 2015)
Number of patients with neonatal survival and birth at or after 34.0 weeks of the pump twin [ Time Frame: 2 weeks after expected date of birth ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02621645 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 17, 2015)
  • Number of patients with need for re-intervention [ Time Frame: 2 weeks after expected date of birth ]
    This means any kind of fetal intervention, such as repeated intrafetal coagulation, intra-uterine transfusion cord-occlusion...
  • Number of patients with maternal morbidity [ Time Frame: 2 weeks after expected date of birth ]
    Maternal morbidity is defined as presence of one or more of the following events:
    • Need for transfusion for hemorrhage
    • Abruption
    • Chorioamnionitis as defined on pathology
    • Sepsis
    • Bowel perforation
    • Other serious maternal morbidity requiring admission to ICU
  • Number of patients with miscarriage [ Time Frame: 2 weeks after expected date of birth ]
    Number of patients with miscarriage before 24 weeks
  • Number of patients with preterm prelabor rupture of membranes (PPROM) [ Time Frame: 2 weeks after expected date of birth ]
    Number of patients with rupture of membranes before onset of labor and before 37 weeks
  • Number of patients with preterm birth prior to 28 weeks [ Time Frame: 2 weeks after expected date of birth ]
    Number of patients delivering before 28 weeks
  • Number of patients with preterm birth prior to 32 weeks [ Time Frame: 2 weeks after expected date of birth ]
    Number of patients delivering before 32 weeks
  • Number of patients with preterm birth prior to 37 weeks [ Time Frame: 2 weeks after expected date of birth ]
    Number of patients delivering before 37 weeks
  • Time from randomization to delivery [ Time Frame: 2 weeks after expected date of birth ]
    Number of weeks between randomization and the time of delivery
  • Time from randomization to PPROM [ Time Frame: 2 weeks after expected date of birth ]
    Number of weeks between randomization and rupture of membranes in patients with PPROM
  • Birth weight in grams [ Time Frame: 42 days (28 days neonatal period+2 weeks postdates) after expected date of birth ]
  • Number of patients with stillbirth [ Time Frame: 42 days (28 days neonatal period+2 weeks postdates) after expected date of birth ]
    Stillbirth refers to all patients with antepartum or intrapartum demise of the fetus
  • Number of patients with neonatal death [ Time Frame: 42 days (28 days neonatal period+2 weeks postdates) after expected date of birth ]
    Demise of a live-born child within the first 28 days of life
  • Number of patients with severe neonatal morbidity [ Time Frame: 42 days (28 days neonatal period+2 weeks postdates) after expected date of birth ]
    Severe neonatal morbidity is defined as the presence of at least one of the following:
    • chronic lung disease (defined as oxygen dependency at 36 weeks gestational age)
    • patent ductus arteriosus needing medical therapy or surgical closure
    • necrotizing enterocolitis stage 2 or higher
    • retinopathy of prematurity stage 3 or higher
    • ischemic limb injury
    • amniotic band syndrome
    • severe cerebral injury (includes at least one of the following: 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).
  • High volume vs low volume centers of neonatal survival and birth at or after 34.0 weeks of the pump twin and maternal morbidity parameters [ Time Frame: 2 weeks after expected date of birth ]
  • Number of patients with intact survival rate [ Time Frame: 2 years after expected date of birth ]
    Intact survival rate defined as the number of surviving infants with normal development at two years corrected for prematurity as assessed by the ASQ® score for infant development (Ages & Stages Questionnaire). A score of more than 2 standard deviations below the mean score for term-born children will be considered abnormal.
  • Number of patients with normal Bayley III score [ Time Frame: 2 years after expected date of birth ]
    Number of patients with normal Bayley III score at two years of age corrected for prematurity
Original Secondary Outcome Measures  ICMJE
 (submitted: December 2, 2015)
  • Number of patients with need for re-intervention [ Time Frame: 2 weeks after expected date of birth ]
    This means any kind of fetal intervention, such as repeated intrafetal coagulation, intra-uterine transfusion cord-occlusion...
  • Number of patients with maternal morbidity [ Time Frame: 2 weeks after expected date of birth ]
    Maternal morbidity is defined as presence of one or more of the following events:
    • Need for transfusion for hemorrhage
    • Abruption
    • Chorioamnionitis as defined on pathology
    • Sepsis
    • Bowel perforation
    • Other serious maternal morbidity requiring admission to ICU
  • Number of patients with miscarriage [ Time Frame: 2 weeks after expected date of birth ]
    Number of patients with miscarriage before 24 weeks
  • Number of patients with preterm prelabor rupture of membranes (PPROM) [ Time Frame: 2 weeks after expected date of birth ]
    Number of patients with rupture of membranes before onset of labor and before 37 weeks
  • Number of patients with preterm birth prior to 28 weeks [ Time Frame: 2 weeks after expected date of birth ]
    Number of patients delivering before 28 weeks
  • Number of patients with preterm birth prior to 32 weeks [ Time Frame: 2 weeks after expected date of birth ]
    Number of patients delivering before 32 weeks
  • Number of patients with preterm birth prior to 37 weeks [ Time Frame: 2 weeks after expected date of birth ]
    Number of patients delivering before 37 weeks
  • Time from radomization to delivery [ Time Frame: 2 weeks after expected date of birth ]
    Number of weeks between radomization and the time of delivery
  • Time from radomization to PPROM [ Time Frame: 2 weeks after expected date of birth ]
    Number of weeks between radomization and rupture of membranes in patients with PPROM
  • Birth weight in grams [ Time Frame: 42 days (28 days neonatal period+2 weeks postdates) after expected date of birth ]
  • Number of patients with stillbirth [ Time Frame: 42 days (28 days neonatal period+2 weeks postdates) after expected date of birth ]
    Stillbirth refers to all patients with antepartum or intrapartum demise of the fetus
  • Number of patients with neonatal death [ Time Frame: 42 days (28 days neonatal period+2 weeks postdates) after expected date of birth ]
    Demise of a live-born child within the first 28 days of life
  • Number of patients with severe neonatal morbidity [ Time Frame: 42 days (28 days neonatal period+2 weeks postdates) after expected date of birth ]
    Severe neonatal morbidity is defined as the presence of at least one of the following:
    • chronic lung disease (defined as oxygen dependency at 36 weeks gestational age)
    • patent ductus arteriosus needing medical therapy or surgical closure
    • necrotizing enterocolitis stage 2 or higher
    • retinopathy of prematurity stage 3 or higher
    • ischemic limb injury
    • amniotic band syndrome
    • severe serebral injury (includes at least one of the following: intraventricular hemorrhage grade 3 or higher, cystic periventricular leukomalacia grade 2 or higher, ventricular dilatation greater than the 97th centilen porencephalic or parenchymal cysts or other severe cerebral lesions).
  • High volume vs low volume centers of neonatal survival and birth at or after 34.0 weeks of the pump twin and maternal morbidity parameters [ Time Frame: 2 weeks after expected date of birth ]
  • Number of patients with intact survival rate [ Time Frame: 2 years after expected date of birth ]
    Intact survival rate defined as the number of surviving infants with normal development at two years corrected for prematurity as assessed by the ASQ® score for infant development (Ages & Stages Questionnaire). A score of more than 2 standard deviations below the mean score for term-born children will be considered abnormal.
  • Number of patients with normal Bayley III score [ Time Frame: 2 years after expected date of birth ]
    Number of patients with normal Bayley III score at two years of age corrected for prematurity
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE TRAP Intervention STudy: Early Versus Late Intervention for Twin Reversed Arterial Perfusion Sequence
Official Title  ICMJE Early Versus Late Intervention for Twin Reversed Arterial Perfusion Sequence: an Open-label Randomized Controlled Trial: TRAPIST - TRAP Intervention STudy
Brief Summary Multi-center open-label randomized controlled trial to assess if early intervention (12.0-14.0 weeks) (study group) improves the outcome of TRAP sequence as compared to late intervention (16.0-19.0 weeks) (control group). The investigators will randomly assign women diagnosed with TRAP sequence diagnosed between 12.0 and 13.6 weeks to an early or late intervention group (1:1), using a web-based application and a computer-generated list with random permuted blocks of sizes 2 or 4 (www.sealedenvelope.com), stratified by gestational age (GA) at inclusion (11.6 -12.6 weeks versus 13.0-13.6 weeks). Analysis will be by intention to treat.
Detailed Description

The investigators propose to conduct a multi-center open-label randomized controlled trial to assess if early intervention (12.0-14.0 weeks) (study group) improves the outcome of TRAP sequence as compared to late intervention (16.0-19.0 weeks) (control group). The investigators will randomly assign women diagnosed with TRAP sequence diagnosed between 11.6 and 13.6 weeks (1:1) to an early or late intervention group, using a web-based application (www.sealedenvelope.com) with a computer-generated list with random permuted blocks of sizes 2 or 4, stratified by gestational age at inclusion (11.6 -12.6 weeks versus 13.0-13.6 weeks). Analysis will be by intention-to-treat. Outcome will be adjudicated blinded to group allocation.

All interventions will be done under local anaesthesia and/or conscious sedation in sterile conditions by an experienced operator. They must be performed within 1 week after randomisation and at the latest at 14.0 weeks in the early group and 19.0 weeks in the late group. In the early group, only intrafetal coagulation will be used. Intrafetal ablation will be performed under ultrasound guidance using an 18-gauge (1.27 mm) to 20-gauge (0.91 mm) needle with a free-hand technique. The needle is introduced into the pelvis/abdomen of the TRAP mass close to the intra-abdominal portion of the feeding vessel, while avoiding puncture of the placenta and pump twin sac. The procedure is considered successful when there is complete cessation of reverse flow into the TRAP mass on intraoperative color-flow mapping.

In the late intervention/control group either intrafetal coagulation or fetoscopic laser coagulation will be performed of the cord and/or anastomosing vessels, unless the flow has stopped spontaneously or demise of the pump twin has occurred in the meantime. Intrafetal coagulation is done as described above by using a 17-gauge (1.47 mm) to 20-gauge needle. Alternatively, fetoscopic laser coagulation of the cord or anastomosing vessels can be performed through a 17-gauge to 7 French trocar with 1-1,3 mm fetoscope and 400 μm laser fiber. The rationale not to standardize the technique in the late intervention group is that several techniques have been reported for treatment after 16 weeks without any significant differences in outcome. Also, it is usual for the surgeon to adapt the technique to the requirements of each individual case, e.g. for a posterior placenta, the surgeon may prefer fetoscopic rather than intrafetal coagulation. Not restricting the technique to only 1 option will therefore more truly represent current practice and increase the generalizability of the trial's findings.

Patients will be discharged the same day or 1 day after the procedure. Management and follow-up will be similar for the study and the control or current practice group. A follow-up scan is usually performed 1 week after the intervention to check for fetal well-being and exclude anemia. A detailed ultrasound scan will be arranged in a fetal medicine center at 20 and 30 weeks to assess the heart and brain anatomy. Some centers may offer an MRI scan at around 30 weeks as part of the protocol for monochorionic twin pregnancies that underwent an intrauterine intervention. Antenatal, peripartum and postnatal care of the mother will be similar to that of a singleton pregnancy and at the discretion of the referring physician. Intrauterine intervention for TRAP sequence is not an indication for cesarean or elective preterm birth.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Twin Reversal Arterial Perfusion Syndrome
Intervention  ICMJE
  • Procedure: Early selective reduction of TRAP mass
    Ultrasound-guided intrafetal ablation using an 18 Gauge to 20 Gauge needle
  • Procedure: Late selective reduction of TRAP mass
    Ultrasound-guided intrafetal ablation using a 17 Gauge to 20 Gauge needle OR fetoscopic laser coagulation of the cord or anastomising vessels through a 17 Gauge to 7 French trocar, with a 1-1,3 mm fetoscope and a 400 µm laser fiber. The treating physician can decide which technique will be used for the selective reduction.
  • Device: Ultrasound-guided intrafetal ablation using a 18 to 20 Gauge needle
  • Device: Ultrasound-guided intrafetal ablation using a 17 to 20 Gauge needle
  • Device: Laser coagulation of the cord or anastomising vessels through a 17 Gauge to 7 French trocar, with a 1-1,3 mm fetoscope and a 400 µm laser fiber
Study Arms  ICMJE
  • Experimental: Early intervention
    Intervention between 12.0 and 14.0 weeks. Early selective reduction of TRAP mass.
    Interventions:
    • Procedure: Early selective reduction of TRAP mass
    • Device: Ultrasound-guided intrafetal ablation using a 18 to 20 Gauge needle
  • Active Comparator: Late intervention
    Intervention between 16.0 and 19.0 weeks. Late selective reduction of TRAP mass. This is the standard timing of the intervention. One of two possible techniques for late reduction is chosen by the treating physician.
    Interventions:
    • Procedure: Late selective reduction of TRAP mass
    • Device: Ultrasound-guided intrafetal ablation using a 17 to 20 Gauge needle
    • Device: Laser coagulation of the cord or anastomising vessels through a 17 Gauge to 7 French trocar, with a 1-1,3 mm fetoscope and a 400 µm laser fiber
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 2, 2015)
126
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2022
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • TRAP sequence in a monochorionic diamniotic twin pregnancy diagnosed between 11.6 and 13.6 weeks, as determined by the crown-rump length of the pump twin in spontaneous conceptions and by the date of insemination or embryonic age at replacement in pregnancies resulting from subfertility treatment
  • Women aged 18 years or more, who are able to consent
  • Anatomically normal pump twin
  • Provide written informed consent to participate in this randomized controlled trial, forms being approved by the Ethical Committees

Exclusion Criteria:

  • Contraindication for an intervention due to a severe maternal medical condition or threatening miscarriage
  • Inaccessibility of the acardiac twin due to a retroverted uterus, severe maternal obesity, uterine fibroids, bowel or placental superposition
  • A major anomaly in the pump twin, requiring surgery or leading to infant death or severe handicap
  • Spontaneous arrest of the reverse flow and/or pump twin demise at diagnosis
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Isabel Couck, MD +32 16 342294 isabel.couck@uzleuven.be
Contact: Liesbeth Lewi, MD PhD +32 16 342862 liesbeth.lewi@uzleuven.be
Listed Location Countries  ICMJE Austria,   Belgium,   Canada,   France,   Germany,   Israel,   Italy,   Netherlands,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02621645
Other Study ID Numbers  ICMJE S58224
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Universitaire Ziekenhuizen Leuven
Study Sponsor  ICMJE Universitaire Ziekenhuizen Leuven
Collaborators  ICMJE
  • St. George's Hospital, University of London (UK sponsor)
  • Leiden University Medical Center
  • Ospedalo Maggiore Policlinico di Milano, Italy
  • Hospital Universitari Vall d'hebron Barcelona, Spain
  • Centro Médico-Chirurgical et Obstétrical (CMCO) Schiltigheim, France
  • Universitätsklinik für Frauenheilkunde und Geburtshilfe Graz, Austria
  • Ospedale dei Bambini "Vittore Buzzi" Milano, Italy
  • Birmingham Women's Hospital, UK
  • Sheba Medical Center Tel-Hashomer, Israel
  • Children's Memorial Hermann Hospital Houston Texas, USA
  • Universitätsklinikum Hamburg-Eppendorf, Germany
  • Mount Sinai Hospital, Canada
  • University of Pittsburgh
  • University Hospital Innsbruck, Austria
  • Spedali Civili, University of Brescia, Italy
Investigators  ICMJE
Study Chair: Liesbeth Lewi, MD PhD UZ Leuven
PRS Account Universitaire Ziekenhuizen Leuven
Verification Date January 2017

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