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This multicenter open-label randomized controlled trial is set up to evaluate the effect of fetoscopic laser surgery on the gestational age at birth for monochorionic twin pregnancies diagnosed with twin anemia-polycythemia sequence. Half op the patients will be treated with fetoscopic laser surgery, while the other half will be managed with standard treatment. The hypothesis is that fetoscopic laser therapy will improve neonatal outcome by prolonging pregnancy.
Rationale: Monochorionic twins share one placenta and are connected to each other via vascular anastomoses at the placental surface, allowing the blood to transfer bi-directionally between the two fetuses. Unbalanced inter-twin blood transfusion can result in twin anemia-polycythemia sequence (TAPS). Management options include: fetoscopic laser surgery, intrauterine blood transfusion (IUT) with or without partial exchange transfusion (PET), preterm delivery, selective feticide and expectant management. The optimal treatment for TAPS is not clear. Fetoscopic laser surgery is the only causative treatment option, but data on the feasibility of this procedure are mainly based on case reports and small cohort studies. A large randomized controlled trial is needed to evaluate the possible beneficial effect of fetoscopic laser surgery and to determine the optimal treatment option for TAPS.
Objective: The aim of this trial is to investigate whether fetoscopic laser surgery improves the outcome for TAPS twins as compared to the control group (standard care consisting of expectant management, IUT, preterm delivery). The hypothesis is that fetoscopic laser therapy will improve neonatal outcome by prolonging pregnancy.
Study design: International multi-centered open-label randomized controlled trial to assess whether fetoscopic laser surgery (experimental group) improves the outcome of TAPS twins compared to standard care (control group).
Study population: Monochorionic twin pregnancies with TAPS stage ≥ 2 (spontaneous or post-laser) diagnosed between 20 and 28 weeks of gestation.
Intervention: In the experimental group fetoscopic laser surgery is performed, whereas the control group is treated with standard care (expectant management, IUT (with PET), selective feticide and/or preterm delivery, depending on the opinion of the fetal surgeon).
Main study endpoints: The primary outcome is gestational age at birth. Secondary outcomes include: perinatal mortality or severe neonatal morbidity, hematological complication, procedure related complications and long-term neurodevelopmental outcome at 2 years.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Fetoscopic Laser Surgery | Experimental | fetoscopic laser coagulation of the vascular anastomoses at the placental surface |
|
| Standard Treatment | Other | Expectant management, IUT (with or without PET), preterm delivery |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fetoscopic Laser Surgery | Procedure | Fetoscopic Photocoagulation of the connecting vascular anastomoses on the surface of the placenta. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Gestational Age at Birth | Gestational age: completed weeks + additional days since the first day of the last menstruational period of the mother. | 2 weeks after expected date of birth |
| Measure | Description | Time Frame |
|---|---|---|
| Number of patients with perinatal mortality | Perinatal mortality is defined as fetal death or neonatal death (demise of a liveborn child within 28 days after birth) | 42 days (28 days neonatal period+2 weeks postdates) after expected date of birth |
| Number of patients with severe neonatal morbidity |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Femke Slaghekke, MD PhD | Contact | +31 71 52 97211 | f.slaghekke@lumc.nl | |
| Lisanne Tollenaar, BSc | Contact | +31653413875 | l.s.a.tollenaar@lumc.nl |
| Name | Affiliation | Role |
|---|---|---|
| Dick Oepkes, MD PhD | Leiden University Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Yale University | Not yet recruiting | New Haven | Connecticut | 208327 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 16516289 | Background | Lopriore E, Middeldorp JM, Oepkes D, Kanhai HH, Walther FJ, Vandenbussche FP. Twin anemia-polycythemia sequence in two monochorionic twin pairs without oligo-polyhydramnios sequence. Placenta. 2007 Jan;28(1):47-51. doi: 10.1016/j.placenta.2006.01.010. Epub 2006 Mar 3. | |
| 16522415 | Background | Robyr R, Lewi L, Salomon LJ, Yamamoto M, Bernard JP, Deprest J, Ville Y. Prevalence and management of late fetal complications following successful selective laser coagulation of chorionic plate anastomoses in twin-to-twin transfusion syndrome. Am J Obstet Gynecol. 2006 Mar;194(3):796-803. doi: 10.1016/j.ajog.2005.08.069. |
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| ID | Term |
|---|---|
| D005330 | Fetofetal Transfusion |
| ID | Term |
|---|---|
| D000751 | Anemia, Neonatal |
| D000740 | Anemia |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| D053685 | Laser Therapy |
| ID | Term |
|---|---|
| D013812 | Therapeutics |
| D055011 | Ablation Techniques |
| D013514 | Surgical Procedures, Operative |
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| Standard Treatment | Other | In the control group, the choices of treatment include expectant management, intrauterine transfusion (IUT) (with or without partial exchange transfusion (PET)) or preterm delivery, depending on the judgment of the fetal surgeon with regard to the gestational age and state of the disease.
|
|
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 |
| Number of patients with hematological complications | Hematological complications are defined as the presence of at least one of the following:
| 2 weeks after expected date of birth |
| Number of patients with procedure-related complications | Procedure-related complications are defined as at least one of the following:
| 2 weeks after expected date of birth |
| Number of patient with mild neurodevelopmental impairment | Mild neurodevelopmental impairment is defined as at least one of the following:
| 2 years after expected date of birth |
| Number of patients with severe neurodevelopmental impairment | Severe neurodevelopmental impairment is defined as at least one of the following:
| 2 years after expected date of birth |
| Number of patients with behavioral problems | Behavioral problems are defined as a T-score ≥ 64 for one of the following broad band scales: total problem score, Internalizing problems (anxious/depressed, withdrawn, somatic complaints), Externalizing problems (rule-breaking, aggressive behavior) as measured with the Child Behaviour Checklist 1.5-5 years | 2 years after expected date of birth |
| Vittore Buzzi Children's Hospital | Recruiting | Milan | Lombardy | 20154 | Italy |
|
| Leiden University Medical Center | Recruiting | Leiden | South Holland | 2333ZA | Netherlands |
|
| Vall d'Hebron University Hospital | Recruiting | Barcelona | 08035 | Spain |
|
| Karolinska University Hospital | Not yet recruiting | Stockholm | Södermanland County | 141 86 | Sweden |
|
| 25790745 | Background | Sananes N, Veujoz M, Severac F, Barthoulot M, Meyer N, Weingertner AS, Kohler M, Guerra F, Gaudineau A, Nisand I, Favre R. Evaluation of the Utility of in utero Treatment of Twin Anemia-Polycythemia Sequence. Fetal Diagn Ther. 2015;38(3):170-8. doi: 10.1159/000380822. Epub 2015 Mar 17. |
| 24706478 | Background | Slaghekke F, Favre R, Peeters SH, Middeldorp JM, Weingertner AS, van Zwet EW, Klumper FJ, Oepkes D, Lopriore E. Laser surgery as a management option for twin anemia-polycythemia sequence. Ultrasound Obstet Gynecol. 2014 Sep;44(3):304-10. doi: 10.1002/uog.13382. Epub 2014 Aug 4. |
| D007232 |
| Infant, Newborn, Diseases |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |