Randomized Controlled Trial Comparing a Conservative Management and Laser Surgery (TTTS1)

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

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.

Study Overview

• Status: Completed
• Conditions: Infant, Newborn, Diseases; Anemia, Neonatal; Hematologic Disease; Blood and Blood Disorders
• Intervention / Treatment: Procedure: Fetoscopic laser surgery

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 Type: Interventional
• Enrollment (Actual): 179
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, ON M5X 1X5
      • Mount Sinai Hospital, University of Toronto
  • Quebec
    • Montreal, Quebec, Canada, H3T 1R2
      • Hospital Ste-Justine
• France
  • Paris, France, 75006
    • Necker Enfants Malades
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado and Colorado Fetal Care Center
  • Maryland
    • Baltimore, Maryland, United States, 21000
      • University of MD /Department of Obstetrics, Gynecology & Reproductive Sciences
  • Ohio
    • Cincinnati, Ohio, United States, 45229-3026
      • Fetal Care Center of Cincinnati, Cincinnati Children's Hospital Medical Center
    • Columbus, Ohio, United States, 43221
      • The Ohio State University / OSU Fetal Therapy Program
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Fetal Diagnosis and Treatment, The Children's Hospital of Philadelphia
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Fetal Treatment Program of New England, Hasbro Children's Hospital, The Warren Alpert Medical School of Brown University.
  • Texas
    • Houston, Texas, United States, 77030
      • The Texas Fetal Center, Children's Memorial Hermann Hospital, University of Texas Medical School
  • Washington
    • Kirkland, Washington, United States, 98034
      • Fetal Therapy Program, Evergrenn Hospital Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NO INTERVENTION	Procedure: Fetoscopic laser surgery; Fetoscopic laser surgery
Active Comparator: fetoscopic laser	Procedure: Fetoscopic laser surgery; Fetoscopic laser surgery

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2011
• Primary Completion (Actual): September 30, 2018
• Study Completion (Actual): March 31, 2019

Study Registration Dates

• First Submitted: October 11, 2010
• First Submitted That Met QC Criteria: October 11, 2010
• First Posted (Estimate): October 13, 2010

Study Record Updates

• Last Update Posted (Actual): July 20, 2020
• Last Update Submitted That Met QC Criteria: July 17, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Fetoscopic Laser surgery; Stage 1 Twin - twin transfusion syndrome
• Additional Relevant MeSH Terms: Anemia; Hematologic Diseases; Anemia, Neonatal; Infant, Newborn, Diseases
• Other Study ID Numbers: K090601; ID RCB : 2010-A00026-33 (Other Identifier: AFSSAPS)