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

NCT ID: NCT02621645

Last Updated: 2024-07-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

126 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-05-31

Study Completion Date

2025-06-30

Brief Summary

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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

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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.

Conditions

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Twin Reversal Arterial Perfusion Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Early intervention

Intervention between 12.0 and 14.0 weeks. Early selective reduction of TRAP mass.

Group Type EXPERIMENTAL

Early selective reduction of TRAP mass

Intervention Type PROCEDURE

Ultrasound-guided intrafetal ablation using an 18 Gauge to 20 Gauge needle

Ultrasound-guided intrafetal ablation using a 18 to 20 Gauge needle

Intervention Type DEVICE

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.

Group Type ACTIVE_COMPARATOR

Late selective reduction of TRAP mass

Intervention Type PROCEDURE

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.

Ultrasound-guided intrafetal ablation using a 17 to 20 Gauge needle

Intervention Type 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

Intervention Type DEVICE

Interventions

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Early selective reduction of TRAP mass

Ultrasound-guided intrafetal ablation using an 18 Gauge to 20 Gauge needle

Intervention Type 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.

Intervention Type PROCEDURE

Ultrasound-guided intrafetal ablation using a 18 to 20 Gauge needle

Intervention Type DEVICE

Ultrasound-guided intrafetal ablation using a 17 to 20 Gauge needle

Intervention Type 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

Intervention Type DEVICE

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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St. George's Hospital, University of London (UK sponsor)

UNKNOWN

Sponsor Role collaborator

Leiden University Medical Center

OTHER

Sponsor Role collaborator

Ospedalo Maggiore Policlinico di Milano, Italy

UNKNOWN

Sponsor Role collaborator

Hospital Universitari Vall d'hebron Barcelona, Spain

UNKNOWN

Sponsor Role collaborator

Centro Médico-Chirurgical et Obstétrical (CMCO) Schiltigheim, France

UNKNOWN

Sponsor Role collaborator

Universitätsklinik für Frauenheilkunde und Geburtshilfe Graz, Austria

UNKNOWN

Sponsor Role collaborator

Ospedale dei Bambini "Vittore Buzzi" Milano, Italy

UNKNOWN

Sponsor Role collaborator

Birmingham Women's Hospital, UK

UNKNOWN

Sponsor Role collaborator

Sheba Medical Center

OTHER_GOV

Sponsor Role collaborator

Children's Memorial Hermann Hospital Houston Texas, USA

UNKNOWN

Sponsor Role collaborator

Universitätsklinikum Hamburg-Eppendorf, Germany

UNKNOWN

Sponsor Role collaborator

Mount Sinai Hospital, Canada

OTHER

Sponsor Role collaborator

University of Pittsburgh

OTHER

Sponsor Role collaborator

University Hospital Innsbruck, Austria

UNKNOWN

Sponsor Role collaborator

Spedali Civili, University of Brescia, Italy

UNKNOWN

Sponsor Role collaborator

Universitaire Ziekenhuizen KU Leuven

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Liesbeth Lewi, MD PhD

Role: STUDY_CHAIR

UZ Leuven

Locations

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Children's Memorial Hermann Hospital

Houston, Texas, United States

Site Status RECRUITING

Universitätsklinik für Frauenheilkunde und Geburtshilfe

Graz, , Austria

Site Status RECRUITING

Universitaire Ziekenhuizen Leuven

Leuven, , Belgium

Site Status RECRUITING

Mount Sinai Hospital

Toronto, , Canada

Site Status RECRUITING

Centre Médico-Chirurgical et Obstétrical

Schiltigheim, , France

Site Status RECRUITING

Universitätsklinikum Hamburg-Eppendorf

Hamburg, , Germany

Site Status RECRUITING

Sheba Medical Center

Tel Litwinsky, , Israel

Site Status RECRUITING

Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Milan, , Italy

Site Status RECRUITING

Ospedale dei Bambini Vittore Buzzi

Milan, , Italy

Site Status RECRUITING

Leiden University Medical Center

Leiden, , Netherlands

Site Status RECRUITING

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Site Status RECRUITING

Birmingham Women's Hospital

Birmingham, , United Kingdom

Site Status RECRUITING

King's College

London, , United Kingdom

Site Status RECRUITING

St. George's Hospital, University of London (UK sponsor)

London, , United Kingdom

Site Status RECRUITING

Countries

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United States Austria Belgium Canada France Germany Israel Italy Netherlands Spain United Kingdom

Central Contacts

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Isabel Couck, MD

Role: CONTACT

+32 16 342294

Liesbeth Lewi, MD PhD

Role: CONTACT

+32 16 342862

Facility Contacts

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Anthony Johnson

Role: primary

Noemi Boring

Role: backup

Philipp Klaritsch

Role: primary

Liesbeth Lewi

Role: primary

Tim Van Mieghem

Role: primary

Greg Ryan

Role: backup

Romain Favre

Role: primary

Christian Bamberg

Role: primary

Yoav Yinon

Role: primary

Nicola Persico

Role: primary

Mariano Lanna

Role: primary

Dick Oepkes

Role: primary

Monique Haak

Role: backup

Carlota Rodo

Role: primary

Mark Kilby

Role: primary

Sarah Bower

Role: primary

Asma Khalil

Role: primary

Sarah Davies

Role: backup

References

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Moore TR, Gale S, Benirschke K. Perinatal outcome of forty-nine pregnancies complicated by acardiac twinning. Am J Obstet Gynecol. 1990 Sep;163(3):907-12. doi: 10.1016/0002-9378(90)91094-s.

Reference Type BACKGROUND
PMID: 2206078 (View on PubMed)

Pagani G, D'Antonio F, Khalil A, Papageorghiou A, Bhide A, Thilaganathan B. Intrafetal laser treatment for twin reversed arterial perfusion sequence: cohort study and meta-analysis. Ultrasound Obstet Gynecol. 2013 Jul;42(1):6-14. doi: 10.1002/uog.12495.

Reference Type BACKGROUND
PMID: 23640771 (View on PubMed)

Hecher K, Lewi L, Gratacos E, Huber A, Ville Y, Deprest J. Twin reversed arterial perfusion: fetoscopic laser coagulation of placental anastomoses or the umbilical cord. Ultrasound Obstet Gynecol. 2006 Oct;28(5):688-91. doi: 10.1002/uog.3816.

Reference Type BACKGROUND
PMID: 16958150 (View on PubMed)

Chaveeva P, Poon LC, Sotiriadis A, Kosinski P, Nicolaides KH. Optimal method and timing of intrauterine intervention in twin reversed arterial perfusion sequence: case study and meta-analysis. Fetal Diagn Ther. 2014;35(4):267-79. doi: 10.1159/000358593. Epub 2014 Apr 16.

Reference Type BACKGROUND
PMID: 24751835 (View on PubMed)

Lewi L, Valencia C, Gonzalez E, Deprest J, Nicolaides KH. The outcome of twin reversed arterial perfusion sequence diagnosed in the first trimester. Am J Obstet Gynecol. 2010 Sep;203(3):213.e1-4. doi: 10.1016/j.ajog.2010.04.018. Epub 2010 Jun 3.

Reference Type BACKGROUND
PMID: 20522408 (View on PubMed)

O'Donoghue K, Barigye O, Pasquini L, Chappell L, Wimalasundera RC, Fisk NM. Interstitial laser therapy for fetal reduction in monochorionic multiple pregnancy: loss rate and association with aplasia cutis congenita. Prenat Diagn. 2008 Jun;28(6):535-43. doi: 10.1002/pd.2025.

Reference Type BACKGROUND
PMID: 18509857 (View on PubMed)

Scheier M, Molina FS. Outcome of twin reversed arterial perfusion sequence following treatment with interstitial laser: a retrospective study. Fetal Diagn Ther. 2012;31(1):35-41. doi: 10.1159/000334156. Epub 2011 Dec 23.

Reference Type BACKGROUND
PMID: 22204966 (View on PubMed)

Berg C, Holst D, Mallmann MR, Gottschalk I, Gembruch U, Geipel A. Early vs late intervention in twin reversed arterial perfusion sequence. Ultrasound Obstet Gynecol. 2014 Jan;43(1):60-4. doi: 10.1002/uog.12578.

Reference Type BACKGROUND
PMID: 23908075 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20215730 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16522413 (View on PubMed)

Kerstjens JM, Nijhuis A, Hulzebos CV, van Imhoff DE, van Wassenaer-Leemhuis AG, van Haastert IC, Lopriore E, Katgert T, Swarte RM, van Lingen RA, Mulder TL, Laarman CR, Steiner K, Dijk PH. The Ages and Stages Questionnaire and Neurodevelopmental Impairment in Two-Year-Old Preterm-Born Children. PLoS One. 2015 Jul 20;10(7):e0133087. doi: 10.1371/journal.pone.0133087. eCollection 2015.

Reference Type BACKGROUND
PMID: 26193474 (View on PubMed)

Other Identifiers

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S58224

Identifier Type: -

Identifier Source: org_study_id

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