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

September 19, 2017 updated by: Universitaire Ziekenhuizen KU Leuven

Early Versus Late Intervention for Twin Reversed Arterial Perfusion Sequence: an Open-label Randomized Controlled Trial: TRAPIST - TRAP Intervention STudy

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Anticipated)

126

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Graz, Austria
        • Recruiting
        • Universitätsklinik für Frauenheilkunde und Geburtshilfe
        • Contact:
          • Philipp Klaritsch
  • Belgium
      • Leuven, Belgium
        • Recruiting
        • Universitaire Ziekenhuizen Leuven
        • Contact:
          • Liesbeth Lewi
  • Canada
      • Toronto, Canada
        • Recruiting
        • Mount Sinai Hospital
        • Contact:
          • Tim Van Mieghem
        • Contact:
          • Greg Ryan
  • France
      • Schiltigheim, France
        • Recruiting
        • Centre Médico-Chirurgical et Obstétrical
        • Contact:
          • Romain Favre
  • Germany
      • Hamburg, Germany
        • Recruiting
        • Universitätsklinikum Hamburg-Eppendorf
        • Contact:
          • Christian Bamberg
  • Israel
      • Tel Hashomer, Israel
        • Recruiting
        • Sheba Medical Center
        • Contact:
          • Yoav Yinon
  • Italy
      • Milan, Italy
        • Recruiting
        • Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
        • Contact:
          • Nicola Persico
      • Milan, Italy
        • Recruiting
        • Ospedale dei Bambini Vittore Buzzi
        • Contact:
          • Mariano Lanna
  • Netherlands
      • Leiden, Netherlands
        • Recruiting
        • Leiden University Medical Center
        • Contact:
          • Dick Oepkes
        • Contact:
          • Monique Haak
  • Spain
      • Barcelona, Spain
        • Recruiting
        • Hospital Universitari Vall d'Hebron
        • Contact:
          • Carlota Rodo
  • United Kingdom
      • Birmingham, United Kingdom
        • Recruiting
        • Birmingham Women's Hospital
        • Contact:
          • Mark Kilby
      • London, United Kingdom
        • Recruiting
        • King's College
        • Contact:
          • Sarah Bower
      • London, United Kingdom
        • Recruiting
        • St. George's Hospital, University of London (UK sponsor)
        • Contact:
          • Asma Khalil
        • Contact:
          • Sarah Davies
  • United States
    • Texas
      • Houston, Texas, United States
        • Recruiting
        • Children's Memorial Hermann Hospital
        • Contact:
          • Anthony Johnson
        • Contact:
          • Noemi Boring

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Early intervention
Intervention between 12.0 and 14.0 weeks. Early selective reduction of TRAP mass.
Procedure: Early selective reduction of TRAP mass
Ultrasound-guided intrafetal ablation using an 18 Gauge to 20 Gauge needle
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.
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 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
2 weeks after expected date of birth

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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...
2 weeks after expected date of birth
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
2 weeks after expected date of birth
Number of patients with miscarriage
Time Frame: 2 weeks after expected date of birth
Number of patients with miscarriage before 24 weeks
2 weeks after expected date of birth
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
2 weeks after expected date of birth
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
2 weeks after expected date of birth
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
2 weeks after expected date of birth
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
2 weeks after expected date of birth
Time from randomization to delivery
Time Frame: 2 weeks after expected date of birth
Number of weeks between randomization and the time of delivery
2 weeks after expected date of birth
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
2 weeks after expected date of birth
Birth weight in grams
Time Frame: 42 days (28 days neonatal period+2 weeks postdates) after expected date of birth
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
42 days (28 days neonatal period+2 weeks postdates) after expected date of birth
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
42 days (28 days neonatal period+2 weeks postdates) after expected date of birth
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).
42 days (28 days neonatal period+2 weeks postdates) after expected date of birth
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
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.
2 years after expected date of birth
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
2 years after expected date of birth

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Universitaire Ziekenhuizen KU Leuven

Collaborators

University of Pittsburgh
Sheba Medical Center
Mount Sinai Hospital, Canada
Leiden University Medical Center
St. George's Hospital, University of London (UK sponsor)
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
Children's Memorial Hermann Hospital Houston Texas, USA
Universitätsklinikum Hamburg-Eppendorf, Germany
University Hospital Innsbruck, Austria
Spedali Civili, University of Brescia, Italy

Investigators

  • Study Chair: Liesbeth Lewi, MD PhD, UZ Leuven

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2016

Primary Completion (Anticipated)

June 1, 2020

Study Completion (Anticipated)

June 1, 2022

Study Registration Dates

First Submitted

November 12, 2015

First Submitted That Met QC Criteria

December 2, 2015

First Posted (Estimate)

December 3, 2015

Study Record Updates

Last Update Posted (Actual)

September 21, 2017

Last Update Submitted That Met QC Criteria

September 19, 2017

Last Verified

January 1, 2017

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • S58224

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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