Clinical trial NCT02621645: TRAP Intervention STudy: Early Versus Late Intervention for Twin Reversed Arterial Perfusion Sequence
Official title: Early Versus Late Intervention for Twin Reversed Arterial Perfusion Sequence: an Open-label Randomized Controlled Trial: TRAPIST - TRAP Intervention STudy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Twin Reversal Arterial Perfusion Syndrome
Keywords: monochorionic
TRAP
acardiac twin
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
Collaborators: name: St. George's Hospital, University of London (UK sponsor)
name: Leiden University Medical Center
name: Ospedalo Maggiore Policlinico di Milano, Italy
name: Hospital Universitari Vall d'hebron Barcelona, Spain
name: Centro Médico-Chirurgical et Obstétrical (CMCO) Schiltigheim, France
name: Universitätsklinik für Frauenheilkunde und Geburtshilfe Graz, Austria
name: Ospedale dei Bambini "Vittore Buzzi" Milano, Italy
name: Birmingham Women's Hospital, UK
name: Sheba Medical Center
name: Children's Memorial Hermann Hospital Houston Texas, USA
name: Universitätsklinikum Hamburg-Eppendorf, Germany
name: Mount Sinai Hospital, Canada
name: University of Pittsburgh
name: University Hospital Innsbruck, Austria
name: Spedali Civili, University of Brescia, Italy
First posted: 2015-12-03
Enrollment: 126
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of patients with neonatal survival and birth at or after 34.0 weeks of the pump twin
timeFrame: 2 weeks after expected date of birth
Secondary outcomes:
measure: Number of patients with need for re-intervention
timeFrame: 2 weeks after expected date of birth
measure: Number of patients with maternal morbidity
timeFrame: 2 weeks after expected date of birth
measure: Number of patients with miscarriage
timeFrame: 2 weeks after expected date of birth
measure: Number of patients with preterm prelabor rupture of membranes (PPROM)
timeFrame: 2 weeks after expected date of birth
measure: Number of patients with preterm birth prior to 28 weeks
timeFrame: 2 weeks after expected date of birth
measure: Number of patients with preterm birth prior to 32 weeks
timeFrame: 2 weeks after expected date of birth
measure: Number of patients with preterm birth prior to 37 weeks
timeFrame: 2 weeks after expected date of birth
measure: Time from randomization to delivery
timeFrame: 2 weeks after expected date of birth
measure: Time from randomization to PPROM
timeFrame: 2 weeks after expected date of birth
measure: Birth weight in grams
timeFrame: 42 days (28 days neonatal period+2 weeks postdates) after expected date of birth
measure: Number of patients with stillbirth
timeFrame: 42 days (28 days neonatal period+2 weeks postdates) after expected date of birth
measure: Number of patients with neonatal death
timeFrame: 42 days (28 days neonatal period+2 weeks postdates) after expected date of birth
measure: Number of patients with severe neonatal morbidity
timeFrame: 42 days (28 days neonatal period+2 weeks postdates) after expected date of birth
measure: 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
timeFrame: 2 weeks after expected date of birth
measure: Number of patients with intact survival rate
timeFrame: 2 years after expected date of birth
measure: Number of patients with normal Bayley III score
timeFrame: 2 years after expected date of birth
Other outcomes:
Locations:
city: Houston
country: United States
facility: Children's Memorial Hermann Hospital
state: Texas
city: Graz
country: Austria
facility: Universitätsklinik für Frauenheilkunde und Geburtshilfe
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen Leuven
city: Toronto
country: Canada
facility: Mount Sinai Hospital
city: Schiltigheim
country: France
facility: Centre Médico-Chirurgical et Obstétrical
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: Tel Hashomer
country: Israel
facility: Sheba Medical Center
city: Milan
country: Italy
facility: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
city: Milan
country: Italy
facility: Ospedale dei Bambini Vittore Buzzi
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Birmingham
country: United Kingdom
facility: Birmingham Women's Hospital
city: London
country: United Kingdom
facility: King's College
city: London
country: United Kingdom
facility: St. George's Hospital, University of London (UK sponsor)
Study officials:
affiliation: UZ Leuven
name: Liesbeth Lewi, MD PhD
role: STUDY_CHAIR
References:
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citation: Jelin E, Hirose S, Rand L, Curran P, Feldstein V, Guevara-Gallardo S, Jelin A, Gonzales K, Goldstein R, Lee H. Perinatal outcome of conservative management versus fetal intervention for twin reversed arterial perfusion sequence with a small acardiac twin. Fetal Diagn Ther. 2010;27(3):138-41. doi: 10.1159/000295176. Epub 2010 Mar 9.
citation: Lewi L, Gratacos E, Ortibus E, Van Schoubroeck D, Carreras E, Higueras T, Perapoch J, Deprest J. Pregnancy and infant outcome of 80 consecutive cord coagulations in complicated monochorionic multiple pregnancies. Am J Obstet Gynecol. 2006 Mar;194(3):782-9. doi: 10.1016/j.ajog.2005.09.013.
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