Randomized Controlled Trial Comparing a Conservative Management and Laser Surgery

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Cluster Randomized Trial Comparing a Conservative Management and Primary Laser Surgery

Conditions
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Blood and Blood Disorders, Anemia, Neonatal, Hematologic Disease, Infant, Newborn, Diseases

Intervention / Treatment
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* Procedure: Fetoscopic laser surgery


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NO INTERVENTION<br> | Procedure: Fetoscopic laser surgery<br>* Fetoscopic laser surgery<br>|
| Active Comparator: fetoscopic laser<br> | Procedure: Fetoscopic laser surgery<br>* Fetoscopic laser surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| survival and neurological morbidity at the age of 6 months for each foetus randomized |  | 6 MONTHS | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fetoscopic Laser surgery, Stage 1 Twin - twin transfusion syndrome