Long term Follow-up of the TREOCAPA (Prophylactic TREatment Of the duCtus Arteriosus in Preterm infants by Acetaminophen) Study (TREOCAPA-LT): protocol and statistical analysis plan
- 1INSERM
Abstract
IntroductionThe TREOCAPA (Prophylactic TREatment Of the duCtus Arteriosus in Preterm infants by Acetaminophen) trial was a pan-European, multi-centre, phase II/III trial investigating the impact of prophylactic paracetamol (also known as acetaminophen) given during the first 5 days of life for children born before 29 weeks gestational age (GA) on survival to 36 weeks post-menstrual age without severe neonatal morbidities. However, due to time restrictions, long-term follow-up was not planned as part of the initial trial despite recommendations for neonatal trials to include endpoints measuring efficacy after discharge from the neonatal unit and on-going debate about the long-term effects of paracetamol in the neonatal period. This protocol describes a study to follow-up participants in the TREOCAPA trial at 2 years corrected age initiated after the trials onset.
Methods and analysisThe TREOCAPA Long Term (TREOCAPA-LT) study population consists of all children included in the TREOCAPA phase III trial in centres in countries participating in the follow-up study who are aged between 23.5 and 27.5 months corrected age during the study period. Families are contacted by the clinical teams and a parent or guardian is invited to complete an internet-based (online) questionnaire. The primary outcome is cognition, as measured by the non-verbal Cognitive Scale standard score from the Parent Report of Childrens Abilities-Revised (PARCA-R) questionnaire. Secondary outcomes are moderate to severe neurodevelopment, health service use and costs. Data will be analysed according to the study groups to which children were randomised in the original TREOCAPA RCT.
Ethics and DisseminationThe TREOCAPA-LT protocol was first approved by ethics committees in France (the studys sponsor) and subsequently by all participating countries. Results from TREOCAPA-LT will be published in open access journals in accordance with the funders regulations.
Registrationhttps://clinicaltrials.gov/study/NCT06064825
Strengths and limitationsO_LIThis follow-up study of a large multi-country randomised controlled trial of paracetamol use in preterm children born below 29 weeks of gestation is the first to examine long term effects of paracetamol without the influence of potential confounding factors in this vulnerable population. C_LIO_LIThe study builds on an existing questionnaire in multiple European languages to assess cognition at 2 years of corrected age (PARCA-R) using newly developed questions to permit assessment of overall neurodevelopmental abilities as well as health economic analyses. C_LIO_LISupport in designing the study by the Global Foundation for Care of Newborn Infants (GFCNI) ensures that the study is relevant to patients and their families, and promotes knowledge sharing and public understanding of innovative research in neonatal care and preterm health. C_LIO_LIDespite differing regulatory and ethical requirements for participation between countries which caused some delays in study initiation, the number of eligible children is on target to achieve >80% power to detect a difference of 4.5 IQ points on a standardised scale - below the threshold of 6 which is considered clinically important. C_LI
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BibTeX
@misc{morgan2026long,
title = {{Long term Follow-up of the TREOCAPA (Prophylactic TREatment Of the duCtus Arteriosus in Preterm infants by Acetaminophen) Study (TREOCAPA-LT): protocol and statistical analysis plan}},
author = {A. S. Morgan and J.-C. Roze and M. Ursino and C. Alberti and V. Desplebin and M. Durox and R. Hankard and M. Hamrit and S. J. Johnson and R. Kemper and Y. Marcon and M. Michel and J. Zeitlin and G. Cambonie},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.30.26364424},
url = {https://www.medrxiv.org/content/10.64898/2026.09.30.26364424v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Long term Follow-up of the TREOCAPA (Prophylactic TREatment Of the duCtus Arteriosus in Preterm infants by Acetaminophen) Study (TREOCAPA-LT): protocol and statistical analysis plan
AU - A. S. Morgan
AU - J.-C. Roze
AU - M. Ursino
AU - C. Alberti
AU - V. Desplebin
AU - M. Durox
AU - R. Hankard
AU - M. Hamrit
AU - S. J. Johnson
AU - R. Kemper
AU - Y. Marcon
AU - M. Michel
AU - J. Zeitlin
AU - G. Cambonie
PY - 2026
DA - 2026/09/30
PB - medRxiv
DO - 10.64898/2026.09.30.26364424
UR - https://www.medrxiv.org/content/10.64898/2026.09.30.26364424v1
AB - IntroductionThe TREOCAPA (Prophylactic TREatment Of the duCtus Arteriosus in Preterm infants by Acetaminophen) trial was a pan-European, multi-centre, phase II/III trial investigating the impact of prophylactic paracetamol (also known as acetaminophen) given during the first 5 days of life for children born before 29 weeks gestational age (GA) on survival to 36 weeks post-menstrual age without severe neonatal morbidities. However, due to time restrictions, long-term follow-up was not planned as part of the initial trial despite recommendations for neonatal trials to include endpoints measuring efficacy after discharge from the neonatal unit and on-going debate about the long-term effects of paracetamol in the neonatal period. This protocol describes a study to follow-up participants in the TREOCAPA trial at 2 years corrected age initiated after the trials onset. Methods and analysisThe TREOCAPA Long Term (TREOCAPA-LT) study population consists of all children included in the TREOCAPA phase III trial in centres in countries participating in the follow-up study who are aged between 23.5 and 27.5 months corrected age during the study period. Families are contacted by the clinical teams and a parent or guardian is invited to complete an internet-based (online) questionnaire. The primary outcome is cognition, as measured by the non-verbal Cognitive Scale standard score from the Parent Report of Childrens Abilities-Revised (PARCA-R) questionnaire. Secondary outcomes are moderate to severe neurodevelopment, health service use and costs. Data will be analysed according to the study groups to which children were randomised in the original TREOCAPA RCT. Ethics and DisseminationThe TREOCAPA-LT protocol was first approved by ethics committees in France (the studys sponsor) and subsequently by all participating countries. Results from TREOCAPA-LT will be published in open access journals in accordance with the funders regulations. Registrationhttps://clinicaltrials.gov/study/NCT06064825 Strengths and limitationsO_LIThis follow-up study of a large multi-country randomised controlled trial of paracetamol use in preterm children born below 29 weeks of gestation is the first to examine long term effects of paracetamol without the influence of potential confounding factors in this vulnerable population. C_LIO_LIThe study builds on an existing questionnaire in multiple European languages to assess cognition at 2 years of corrected age (PARCA-R) using newly developed questions to permit assessment of overall neurodevelopmental abilities as well as health economic analyses. C_LIO_LISupport in designing the study by the Global Foundation for Care of Newborn Infants (GFCNI) ensures that the study is relevant to patients and their families, and promotes knowledge sharing and public understanding of innovative research in neonatal care and preterm health. C_LIO_LIDespite differing regulatory and ethical requirements for participation between countries which caused some delays in study initiation, the number of eligible children is on target to achieve >80% power to detect a difference of 4.5 IQ points on a standardised scale - below the threshold of 6 which is considered clinically important. C_LI
ER -