Clinical trial NCT04432168: The TAPS Trial - Fetoscopic Laser Surgery for Twin Anemia Polycythemia Sequence
Official title: The TAPS Trial - Fetoscopic Laser Surgery for Twin Anemia-Polycythemia Sequence - a Multicenter Open-Label Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Twin Anemia Polycythemia Sequence
Keywords: Monochorionic Twins
Twin-Twin Transfusion Syndrome
Fetoscopic Laser Surgery
Intrauterine Transfusion
Partial Exchange Transfusion
Lead sponsor: Leiden University Medical Center
Sponsor class: OTHER
First posted: 2020-06-16
Enrollment: 44
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Monochorionic twin pregnancy complicated by either spontaneous or post-laser twin anemia polycythemia sequence (TAPS), stage ≥ 2, diagnosed between 20+0 and till 28+0 weeks of gestation
* Women aged 18 years or more, who are able to consent.
* Written informed consent to participate in this randomized controlled trial, forms being approved by the Ethical Committees.

Exclusion Criteria:

* TAPS stage 1
* TAPS stage≥ 2, diagnosed within 1 week after laser surgery for twin-twin transfusion syndrome (TTTS) (a large inter-twin middle cerebral artery peak systolic velocity difference within a week after laser for TTTS is likely to related to hemodynamic reequilibration, and is usually not based on TAPS)
* Triplet pregnancies, or higher order multiple pregnancies
* TAPS cases that already underwent an intrauterine treatment (with the exception of laser surgery for TTTS in post-laser TAPS cases)
* Congenital abnormalities (including severe cerebral injury) in one or both twins

Primary outcomes:
measure: Gestational Age at Birth
timeFrame: 2 weeks after expected date of birth
Secondary outcomes:
measure: Number of patients with perinatal mortality
timeFrame: 42 days (28 days neonatal period+2 weeks postdates) after expected date of birth
measure: Number of patients with severe neonatal morbidity
timeFrame: 42 days (28 days neonatal period+2 weeks postdates) after expected date of birth
measure: Number of patients with hematological complications
timeFrame: 2 weeks after expected date of birth
measure: Number of patients with procedure-related complications
timeFrame: 2 weeks after expected date of birth
measure: Number of patient with mild neurodevelopmental impairment
timeFrame: 2 years after expected date of birth
measure: Number of patients with severe neurodevelopmental impairment
timeFrame: 2 years after expected date of birth
measure: Number of patients with behavioral problems
timeFrame: 2 years after expected date of birth
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Milan
country: Italy
facility: Vittore Buzzi Children's Hospital
state: Lombardy
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
state: South-Holland
city: Barcelona
country: Spain
facility: Vall d'Hebron University Hospital
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
state: Södermanland
Study officials:
affiliation: Leiden University Medical Center
name: Dick Oepkes, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.