Clinical trial NCT01220011: Randomized Controlled Trial Comparing a Conservative Management and Laser Surgery
Official title: A Cluster Randomized Trial Comparing a Conservative Management and Primary Laser Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Blood and Blood Disorders
Anemia, Neonatal
Hematologic Disease
Infant, Newborn, Diseases
Keywords: Fetoscopic Laser surgery
Stage 1 Twin - twin transfusion syndrome
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2010-10-13
Enrollment: 179
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this trial is to compare both strategies (Expectative Vs Fetoscopic laser surgery) for patients with stage 1 TTTS and favorable obstetrical parameters in an international randomized controlled trial. This trial will answer an important question and will help in the management and tailoring of surgical indications in stage 1 TTTS.

Detailed description: Although we demonstrated the overall benefit of fetoscopic laser surgery as first-line treatment in twin-twin transfusion syndrome (TTTS), indications in early stage TTTS are controversial. Indeed, a conservative management with close follow-up is offered in some centers as first-line management for QUINTERO stage 1 TTTS, although this strategy has not been formally compared to first-line fetoscopic placental surgery. The objective of this trial is to compare both strategies for patients with stage 1 TTTS and favorable obstetrical parameters in an international randomized controlled trial. Patients randomized to a conservative management will be followed on a weekly basis as long as the syndrome remains stable using obstetrical and fetal parameters and until an adequate gestational age is reached allowing delivery. Cases progressing to stage ≥ 2 or with a worsening of obstetrical parameters during follow-up in this group will be actively treated by percutaneous laser coagulation. Patients allocated to the "immediate laser" group will be treated by fetoscopic laser surgery within 24 h following randomization. The primary end-point encompasses survival and neurological morbidity at the age of 6 months for each foetus randomized. Analyses and power computations use a cluster-trial methodology that accounts for the inter-twin correlation, with many benefits over more traditional designs using a per-pregnancy outcome. With proportions of 60% and 75% meaning a clinically relevant difference of 15% between the groups, 200 fetuses or equivalently 100 pregnancies would be needed in each arm to reach a power of 80% with an alpha-risk of 5%, allowing 2 interim analyses based upon LAN-DEMETS boundaries and an O'Brien-Fleming function. Inclusion criteria, interventions and randomisation were investigated through a preliminary survey across potential participating centers. Based on this survey, it is anticipated that 3 years will be needed to achieve the requested number of patients. This trial will answer an important question and will help in the management and tailoring of surgical indications in stage 1 TTTS.

Eligibility criteria: Inclusion Criteria:

* TTTS stage 1 (Euro foetus criteria)
* Gestational age \> 16 and \< 26 weeks
* Age \> 18
* Informed consent

Exclusion Criteria:

* Therapeutic amniocentesis prior to referral
* Short cervix \< 15 mm on transvaginal US
* Severe maternal discomfort:Dyspnea and orthopnea, Abdominal pain \> 4 on a 10-level visual analogic pain scale, Contractions \> 1 per hour
* PPROM
* Fetal malformations unrelated to TTTS
* Follow-up is impossible

Primary outcomes:
measure: survival and neurological morbidity at the age of 6 months for each foetus randomized
timeFrame: 6 MONTHS
Secondary outcomes:
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Children's Hospital Colorado and Colorado Fetal Care Center
state: Colorado
city: Baltimore
country: United States
facility: University of MD /Department of Obstetrics, Gynecology & Reproductive Sciences
state: Maryland
city: Cincinnati
country: United States
facility: Fetal Care Center of Cincinnati, Cincinnati Children's Hospital Medical Center
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University / OSU Fetal Therapy Program
state: Ohio
city: Philadelphia
country: United States
facility: Fetal Diagnosis and Treatment, The Children's Hospital of Philadelphia
state: Pennsylvania
city: Providence
country: United States
facility: Fetal Treatment Program of New England, Hasbro Children's Hospital, The Warren Alpert Medical School of Brown University.
state: Rhode Island
city: Houston
country: United States
facility: The Texas Fetal Center, Children's Memorial Hermann Hospital, University of Texas Medical School
state: Texas
city: Kirkland
country: United States
facility: Fetal Therapy Program, Evergrenn Hospital Medical Center
state: Washington
city: Toronto
country: Canada
facility: Mount Sinai Hospital, University of Toronto
state: Ontario
city: Montreal
country: Canada
facility: Hospital Ste-Justine
state: Quebec
city: Paris
country: France
facility: Necker Enfants Malades
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Yves VILLE, PUPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Stirnemann J, Slaghekke F, Khalek N, Winer N, Johnson A, Lewi L, Massoud M, Bussieres L, Aegerter P, Hecher K, Senat MV, Ville Y. Intrauterine fetoscopic laser surgery versus expectant management in stage 1 twin-to-twin transfusion syndrome: an international randomized trial. Am J Obstet Gynecol. 2021 May;224(5):528.e1-528.e12. doi: 10.1016/j.ajog.2020.11.031. Epub 2020 Nov 26.