Safety and Outcomes in Infants Born to Mothers Participating in Retosiban Treatment Trials: ARIOS Follow-Up Study

Marcy Powell, George Saade, Steve Thornton, Jeanne M. Pimenta, Nazneen Haque, Diane Miller, Kathleen J. Beach, Jerry Snidow, Erika Ochoa Correa, Rhona Scott

Research output: Contribution to journalArticlepeer-review

Abstract

Objective  Retosiban, an oxytocin receptor antagonist, was developed for treating spontaneous preterm labor (sPTL) in women with intact membranes. This ARIOS follow-up study aimed to characterize clinical safety, morbidity, and mortality of infants exposed to retosiban or comparator over 2 years. Study Design  ARIOS prospectively assessed outcomes in infants whose mothers received at least one dose of retosiban or comparator (placebo/atosiban) in two Phase 3 sPTL trials. Both trials were terminated prematurely owing to poor enrolment. Infants could be enrolled into ARIOS from 28 days after estimated due date until hospital discharge or up to 9 months (corrected age). An internally developed questionnaire detailing medical conditions, mortality and resource use (Child Health Inventory; CHI), Ages and Stages Questionnaire-3 (ASQ-3), Modified Checklist for Autism in Toddlers-Revised with Follow-Up, and Child Behavior Checklist for Ages 1.5 to 5 were completed remotely by parents or legal guardians at prespecified intervals. Serious adverse events (SAEs) were primarily captured via CHI. No comparative statistical analysis was conducted between treatment arms. Results  A total of 49 (86%) infants who had received retosiban and 49 (78%) infants who had received a comparator were enrolled in ARIOS. No deaths occurred during the study. Nine infants experienced SAEs: 6/49 (12.2%) infants in the comparators group and 3/49 (6.1%) in the retosiban group. Of the nine SAEs, seven were due to infections, three, and four in the retosiban and comparators groups, respectively. Based on ASQ-3 score, the incidence of neurodevelopmental delay at 18 and 24 months were 0/18 (0%) and 2/25 (8%) with retosiban and 7/22 (31.8%) and 3/21 (14.3%) with comparator, respectively. Conclusion  The current study showed no unexpected adverse outcome or impairment with retosiban based on safety monitoring and neurodevelopment assessments. No further follow-up is intended owing to the discontinuation of clinical development of retosiban. Key Points There is a need for an effective and safe treatment for sPTL. ARIOS was a follow-up study of two Phase 3 trials in sPTL. There were no safety concerns with retosiban treatment. Slow recruitment led to termination of the Phase 3 trials.

Original languageEnglish (US)
JournalAmerican Journal of Perinatology
DOIs
StateAccepted/In press - 2021
Externally publishedYes

Keywords

  • neurodevelopment
  • oxytocin receptor antagonists
  • preterm birth
  • retosiban

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Obstetrics and Gynecology

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