Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| St. George's Hospital, University of London (UK sponsor) | UNKNOWN |
| Leiden University Medical Center | OTHER |
| Ospedalo Maggiore Policlinico di Milano, Italy | UNKNOWN |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Early intervention | Experimental | Intervention between 12.0 and 14.0 weeks. Early selective reduction of TRAP mass. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Early selective reduction of TRAP mass | Procedure | Ultrasound-guided intrafetal ablation using an 18 Gauge to 20 Gauge needle |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Number of patients with maternal morbidity |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Isabel Couck, MD | Contact | +32 16 342294 | isabel.couck@uzleuven.be | |
| Liesbeth Lewi, MD PhD | Contact | +32 16 342862 | liesbeth.lewi@uzleuven.be |
| Name | Affiliation | Role |
|---|---|---|
| Liesbeth Lewi, MD PhD | UZ Leuven | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Memorial Hermann Hospital | Recruiting | Houston | Texas | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 2206078 | Background | 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. | |
| 23640771 | Background | 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. |
Not provided
Not provided
Not provided
| Hospital Universitari Vall d'hebron Barcelona, Spain |
| UNKNOWN |
| Centro Médico-Chirurgical et Obstétrical (CMCO) Schiltigheim, France | UNKNOWN |
| Universitätsklinik für Frauenheilkunde und Geburtshilfe Graz, Austria | UNKNOWN |
| Ospedale dei Bambini "Vittore Buzzi" Milano, Italy | UNKNOWN |
| Birmingham Women's Hospital, UK | UNKNOWN |
| Sheba Medical Center | OTHER_GOV |
| Children's Memorial Hermann Hospital Houston Texas, USA | UNKNOWN |
| Universitätsklinikum Hamburg-Eppendorf | OTHER |
| Mount Sinai Hospital, Canada | OTHER |
| University of Pittsburgh | OTHER |
| University Hospital Innsbruck, Austria | UNKNOWN |
| Spedali Civili, University of Brescia, Italy | UNKNOWN |
Not provided
Not provided
Not provided
Not provided
Not provided
| Late selective reduction of TRAP mass | 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 18 to 20 Gauge needle | 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 | Device |
|
Maternal morbidity is defined as presence of one or more of the following events:
|
| 2 weeks after expected date of birth |
| Number of patients with miscarriage | 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) | 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 | Number of patients delivering before 28 weeks | 2 weeks after expected date of birth |
| Number of patients with preterm birth prior to 32 weeks | Number of patients delivering before 32 weeks | 2 weeks after expected date of birth |
| Number of patients with preterm birth prior to 37 weeks | Number of patients delivering before 37 weeks | 2 weeks after expected date of birth |
| Time from randomization to delivery | Number of weeks between randomization and the time of delivery | 2 weeks after expected date of birth |
| 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 |
| Birth weight in grams | 42 days (28 days neonatal period+2 weeks postdates) after expected date of birth |
| 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 |
| 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 |
| Number of patients with severe neonatal morbidity | Severe neonatal morbidity is defined as the presence of at least one of the following:
| 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 | 2 weeks after expected date of birth |
| 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 |
| 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 |
| Universitätsklinik für Frauenheilkunde und Geburtshilfe | Recruiting | Graz | Austria |
|
| Universitaire Ziekenhuizen Leuven | Recruiting | Leuven | Belgium |
|
| Mount Sinai Hospital | Recruiting | Toronto | Canada |
|
| Centre Médico-Chirurgical et Obstétrical | Recruiting | Schiltigheim | France |
|
| Universitätsklinikum Hamburg-Eppendorf | Recruiting | Hamburg | Germany |
|
| Sheba Medical Center | Recruiting | Tel Litwinsky | Israel |
|
| Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico | Recruiting | Milan | Italy |
|
| Ospedale dei Bambini Vittore Buzzi | Recruiting | Milan | Italy |
|
| Leiden University Medical Center | Recruiting | Leiden | Netherlands |
|
| Hospital Universitari Vall d'Hebron | Recruiting | Barcelona | Spain |
|
| Birmingham Women's Hospital | Recruiting | Birmingham | United Kingdom |
|
| King's College | Recruiting | London | United Kingdom |
|
| St. George's Hospital, University of London (UK sponsor) | Recruiting | London | United Kingdom |
|
| 16958150 | Background | 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. |
| 24751835 | Background | 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. |
| 20522408 | Background | 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. |
| 18509857 | Background | 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. |
| 22204966 | Background | 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. |
| 23908075 | Background | 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. |
| 20215730 | Background | 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. |
| 16522413 | Background | 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. |
| 26193474 | Background | 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. |