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

Twin Reversal Arterial Perfusion Syndrome Clinical Trial

— TRAPIST  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02621645
• Other study ID #: S58224
• Status: Recruiting
• Phase: Phase 4
• First received: November 12, 2015
• Last updated: September 19, 2017
• Start date: May 2016
• Est. completion date: June 2022

Study information

• Verified date: January 2017
• Source: Universitaire Ziekenhuizen Leuven
• Contact: Isabel Couck, MD
• Phone: +32 16 342294
• Email: isabel.couck[@]uzleuven.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 126
• Est. completion date: June 2022
• Est. primary completion date: June 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Twin Reversal Arterial Perfusion Syndrome

Intervention

Procedure:
• Early selective reduction of TRAP mass
Ultrasound-guided intrafetal ablation using an 18 Gauge to 20 Gauge needle
• 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

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

• 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

Locations

Country	Name	City	State
Austria	Universitätsklinik für Frauenheilkunde und Geburtshilfe	Graz
Belgium	Universitaire Ziekenhuizen Leuven	Leuven
Canada	Mount Sinai Hospital	Toronto
France	Centre Médico-Chirurgical et Obstétrical	Schiltigheim
Germany	Universitätsklinikum Hamburg-Eppendorf	Hamburg
Israel	Sheba Medical Center	Tel Hashomer
Italy	Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico	Milan
Italy	Ospedale dei Bambini Vittore Buzzi	Milan
Netherlands	Leiden University Medical Center	Leiden
Spain	Hospital Universitari Vall d'Hebron	Barcelona
United Kingdom	Birmingham Women's Hospital	Birmingham
United Kingdom	King's College	London
United Kingdom	St. George's Hospital, University of London (UK sponsor)	London
United States	Children's Memorial Hermann Hospital	Houston	Texas

Sponsors (16)

Lead Sponsor

Collaborator

Universitaire Ziekenhuizen Leuven

Birmingham Women's Hospital, UK, Centro Médico-Chirurgical et Obstétrical (CMCO) Schiltigheim, France, Children's Memorial Hermann Hospital Houston Texas, USA, Hospital Universitari Vall d'hebron Barcelona, Spain, Leiden University Medical Center, Mount Sinai Hospital, Canada, Ospedale dei Bambini "Vittore Buzzi" Milano, Italy, Ospedalo Maggiore Policlinico di Milano, Italy, Sheba Medical Center Tel-Hashomer, Israel, Spedali Civili, University of Brescia, Italy, St. George's Hospital, University of London (UK sponsor), Universitätsklinik für Frauenheilkunde und Geburtshilfe Graz, Austria, Universitätsklinikum Hamburg-Eppendorf, Germany, University Hospital Innsbruck, Austria, University of Pittsburgh School of Medicine, USA

Countries where clinical trial is conducted

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

References & Publications (11)

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. — View Citation

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. — View Citation

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. — View 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. — View Citation

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. — View 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Number of patients with need for re-intervention	This means any kind of fetal intervention, such as repeated intrafetal coagulation, intra-uterine transfusion cord-occlusion...	2 weeks after expected date of birth
Secondary	Number of patients with maternal morbidity	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
Secondary	Number of patients with miscarriage	Number of patients with miscarriage before 24 weeks	2 weeks after expected date of birth
Secondary	Number of patients with preterm prelabor rupture of membranes (PPROM)	Number of patients with rupture of membranes before onset of labor and before 37 weeks	2 weeks after expected date of birth
Secondary	Number of patients with preterm birth prior to 28 weeks	Number of patients delivering before 28 weeks	2 weeks after expected date of birth
Secondary	Number of patients with preterm birth prior to 32 weeks	Number of patients delivering before 32 weeks	2 weeks after expected date of birth
Secondary	Number of patients with preterm birth prior to 37 weeks	Number of patients delivering before 37 weeks	2 weeks after expected date of birth
Secondary	Time from randomization to delivery	Number of weeks between randomization and the time of delivery	2 weeks after expected date of birth
Secondary	Time from randomization to PPROM	Number of weeks between randomization and rupture of membranes in patients with PPROM	2 weeks after expected date of birth
Secondary	Birth weight in grams		42 days (28 days neonatal period+2 weeks postdates) after expected date of birth
Secondary	Number of patients with stillbirth	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
Secondary	Number of patients with neonatal death	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
Secondary	Number of patients with severe neonatal morbidity	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
Secondary	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		2 weeks after expected date of birth
Secondary	Number of patients with intact survival rate	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
Secondary	Number of patients with normal Bayley III score	Number of patients with normal Bayley III score at two years of age corrected for prematurity	2 years after expected date of birth