Randomized Controlled Trial Comparing a Conservative Management and Laser Surgery

Not Applicable

Completed

• Conditions: Infant, Newborn, Diseases; Blood and Blood Disorders; Anemia, Neonatal; Hematologic Disease
• Interventions: Procedure: Fetoscopic laser surgery

• Registration Number: NCT01220011
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

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.

Study Timeline

• Study First Submitted: 2010-10-11
• Study First Submitted QC: 2010-10-11
• Study First Posted: 2010-10-13
• Study Start: 2011-04-19
• Primary Completion: 2018-09-30
• Study Completion: 2019-03-31
• Status Verified: 2020-07
• Last Update Submitted: 2020-07-17
• Last Update Posted: 2020-07-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 179

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
fetoscopic laser	Fetoscopic laser surgery	-
NO INTERVENTION	Fetoscopic laser surgery	-

Primary Outcome Measures

Name	Time	Method
survival and neurological morbidity at the age of 6 months for each foetus randomized	6 MONTHS

Trial Locations

Locations (11)

Children's Hospital Colorado and Colorado Fetal Care Center; 🇺🇸 Aurora, Colorado, United States

University of MD /Department of Obstetrics, Gynecology & Reproductive Sciences; 🇺🇸 Baltimore, Maryland, United States

Fetal Care Center of Cincinnati, Cincinnati Children's Hospital Medical Center; 🇺🇸 Cincinnati, Ohio, United States

The Ohio State University / OSU Fetal Therapy Program; 🇺🇸 Columbus, Ohio, United States

Fetal Treatment Program of New England, Hasbro Children's Hospital, The Warren Alpert Medical School of Brown University.; 🇺🇸 Providence, Rhode Island, United States

Fetal Diagnosis and Treatment, The Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States

The Texas Fetal Center, Children's Memorial Hermann Hospital, University of Texas Medical School; 🇺🇸 Houston, Texas, United States

Fetal Therapy Program, Evergrenn Hospital Medical Center; 🇺🇸 Kirkland, Washington, United States

Necker Enfants Malades; 🇫🇷 Paris, France

Mount Sinai Hospital, University of Toronto; 🇨🇦 Toronto, Ontario, Canada

Hospital Ste-Justine; 🇨🇦 Montreal, Quebec, Canada