NCT02621645

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.

Trial Health

68
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
126

participants targeted

Target at P50-P75 for phase_4

Timeline
Completed

Started May 2016

Longer than P75 for phase_4

Geographic Reach
11 countries

14 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 12, 2015

Completed
21 days until next milestone

First Posted

Study publicly available on registry

December 3, 2015

Completed
5 months until next milestone

Study Start

First participant enrolled

May 1, 2016

Completed
9.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2025

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2025

Completed
Last Updated

July 10, 2024

Status Verified

July 1, 2024

Enrollment Period

9.1 years

First QC Date

November 12, 2015

Last Update Submit

July 9, 2024

Conditions

Twin Reversal Arterial Perfusion Syndrome

Keywords

monochorionicTRAPacardiac twin

Outcome Measures

Primary Outcomes (1)

  • Number of patients with neonatal survival and birth at or after 34.0 weeks of the pump twin

    2 weeks after expected date of birth

Secondary Outcomes (16)

  • Number of patients with need for re-intervention

    2 weeks after expected date of birth

  • Number of patients with maternal morbidity

    2 weeks after expected date of birth

  • Number of patients with miscarriage

    2 weeks after expected date of birth

  • Number of patients with preterm prelabor rupture of membranes (PPROM)

    2 weeks after expected date of birth

  • Number of patients with preterm birth prior to 28 weeks

    2 weeks after expected date of birth

  • +11 more secondary outcomes

Study Arms (2)

Early intervention

EXPERIMENTAL

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

Procedure: Early selective reduction of TRAP massDevice: Ultrasound-guided intrafetal ablation using a 18 to 20 Gauge needle

Late intervention

ACTIVE COMPARATOR

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 massDevice: Ultrasound-guided intrafetal ablation using a 17 to 20 Gauge needleDevice: 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

Interventions

Early selective reduction of TRAP massPROCEDURE

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

Early intervention
Late selective reduction of TRAP massPROCEDURE

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.

Late intervention
Ultrasound-guided intrafetal ablation using a 18 to 20 Gauge needleDEVICE
Early intervention
Ultrasound-guided intrafetal ablation using a 17 to 20 Gauge needleDEVICE
Late intervention
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 fiberDEVICE
Late intervention

Eligibility Criteria

Age18 Years+
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (14)

Children's Memorial Hermann Hospital

Houston, Texas, United States

RECRUITING

Universitätsklinik für Frauenheilkunde und Geburtshilfe

Graz, Austria

RECRUITING

Universitaire Ziekenhuizen Leuven

Leuven, Belgium

RECRUITING

Mount Sinai Hospital

Toronto, Canada

RECRUITING

Centre Médico-Chirurgical et Obstétrical

Schiltigheim, France

RECRUITING

Universitätsklinikum Hamburg-Eppendorf

Hamburg, Germany

RECRUITING

Sheba Medical Center

Tel Litwinsky, Israel

RECRUITING

Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Milan, Italy

RECRUITING

Ospedale dei Bambini Vittore Buzzi

Milan, Italy

RECRUITING

Leiden University Medical Center

Leiden, Netherlands

RECRUITING

Hospital Universitari Vall d'Hebron

Barcelona, Spain

RECRUITING

Birmingham Women's Hospital

Birmingham, United Kingdom

RECRUITING

King's College

London, United Kingdom

RECRUITING

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

London, United Kingdom

RECRUITING

Related Publications (11)

  • 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.

    PMID: 2206078BACKGROUND

  • 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.

    PMID: 23640771BACKGROUND

  • 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.

    PMID: 16958150BACKGROUND

  • 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.

    PMID: 24751835BACKGROUND

  • 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.

    PMID: 20522408BACKGROUND

  • 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.

    PMID: 18509857BACKGROUND

  • 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.

    PMID: 22204966BACKGROUND

  • 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.

    PMID: 23908075BACKGROUND

  • 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.

    PMID: 20215730BACKGROUND

  • 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.

    PMID: 16522413BACKGROUND

  • 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.

    PMID: 26193474BACKGROUND

Study Officials

  • Liesbeth Lewi, MD PhD

    UZ Leuven

    STUDY CHAIR

Central Study Contacts

Isabel Couck, MD

CONTACT

+32 16 342294isabel.couck@uzleuven.be

Liesbeth Lewi, MD PhD

CONTACT

+32 16 342862liesbeth.lewi@uzleuven.be

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 12, 2015

First Posted

December 3, 2015

Study Start

May 1, 2016

Primary Completion

June 1, 2025

Study Completion

June 1, 2025

Last Updated

July 10, 2024

Record last verified: 2024-07

Locations

ES(1)AU(1)CA(1)US(1)DE(1)FR(1)GB(3)IL(1)BE(1)IT(2)NL(1)