Real-world data-enabled, 2-randomisation, adaptive trial to determine the clinical efficacy and safety of widely used enteral feeds in preterm babies: the COLLABORATE trial – protocol
12 affiliations
- 1Imperial Clinical Trials Unit, Imperial College London, London, UK
- 2Centre for Reproductive Health, University of Edinburgh Centre for Reproductive Biology, Edinburgh, UK
- 3Department of Neonatology, NHS Lothian, Edinburgh, UK
- 4School of Public Health, Imperial College London, London, UK
- 5School of Medicine, University of Nottingham, Nottingham, UK
- 6Department of Paediatrics, University of Cambridge, Cambridge, UK
- 7Adult Preemie Advocacy Network, London, UK
- 8Bliss, London, UK
- 9Population Health Sciences Institute, Newcastle University Population Health Sciences Institute, Newcastle upon Tyne, UK
- 10Centre for Public Health, Queen’s University Belfast, Belfast, UK
- 11Health Economics Research Centre, University of Oxford, Oxford, UK
- 12Health Data Research UK, London, UK
Abstract
Introduction: Enteral feed type is widely believed to affect brain growth and development directly as well as influencing the risk of necrotising enterocolitis (NEC), a leading cause of death and neuro-impairment in extremely preterm babies. Own mother’s milk (OMM) enhances neurodevelopment and reduces NEC. However, most babies born below 29 weeks gestation require some supplementary feeds during their neonatal unit stay because their mothers are unable to express sufficient milk. The available options, pasteurised human donor milk (pHDM) and preterm formula (PTF), differ markedly in nutrient and non-nutrient composition and cost. Non-definitive data suggest superiority of pHDM over PTF in relation to NEC risk, but no benefits have been shown in important corroboratory outcomes: surgical NEC, death, blood stream infection and neurodevelopmental impairment.
Human milk macronutrient content is variable and often low, hence some clinicians practise routine protein-carbohydrate fortification. Others fear that cow-milk derived fortifiers may increase NEC risk or may provide excessively high protein intakes dangerous to neurodevelopment and metabolic health. These uncertainties compromise patient care and safety and are strong justification for randomised evaluation.
Methods and analysis: COLLABORATE is an efficient UK-wide, real-world data-enabled, 2-randomisation, group-sequential adaptive trial embedded in routine clinical practice. The primary outcome is survival to 34 weeks postmenstrual age without NEC surgery. The aim is to resolve two longstanding nutritional uncertainties for babies born below 29 weeks gestation: whether pHDM or PTF is the optimal supplement should there be an insufficiency of OMM; and whether OMM and pHDM require routine protein-carbohydrate fortification. Based on the assumption that 50% of participants will take part in both randomisations, total recruitment is targeted at 3252 (5% between-arm primary outcome difference; α=0.05; minimum 87% power).
Ethics and dissemination: COLLABORATE is funded by the UK National Institute for Health and Care Research, sponsored by Imperial College London and approved by the UK Health Research Authority (reference 25/LO/0697). Recruitment commenced in April 2026. Results will be shared through academic and lay publications, conferences, workshops, social media and strong personal networks.
Trial registration number: ISRCTN10443084 .
Related
- Efficacy of a personalized, response-based transdiagnostic intervention for emotional disorders delivered via the Internet: a protocol for an adaptive randomized controlled trial
- Metabolic syndrome and colorectal cancer share GPAT3 and PLAU as candidate genes: Mendelian randomisation, machine learning, single-cell knockout and docking
- Distinguishing clinical efficacy from vagal target engagement in perioperative transcutaneous auricular vagus nerve stimulation.
- Evaluation of the clinical efficacy of endoscopic endonasal dacryocystorhinostomy in treating chronic dacryocystitis
- Efficacy and Clinical Predictors of Topical NSAIDs as Bridging Therapy for Diabetic Macular Edema: A Systematic Review and Meta-Analysis
BibTeX
@article{cornelius2026realworld,
title = {{Real-world data-enabled, 2-randomisation, adaptive trial to determine the clinical efficacy and safety of widely used enteral feeds in preterm babies: the COLLABORATE trial – protocol}},
author = {Victoria Cornelius and James P Boardman and David Quine and Sabita Uthaya and Shalini Ojha and Hilary S Wong and Annemarie Lodder and Lauren Ingledow and Peter Bradley and James M S Wason and John Norrie and Ramon Luengo-Fernandez and Andrew Morris and Alex Baker and Ricardo Ribas and Daphne Babalis and Neena Modi},
journal = {BMJ Open},
year = {2026},
month = oct,
doi = {10.1136/bmjopen-2026-125163},
url = {https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2026-125163},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Real-world data-enabled, 2-randomisation, adaptive trial to determine the clinical efficacy and safety of widely used enteral feeds in preterm babies: the COLLABORATE trial – protocol
AU - Victoria Cornelius
AU - James P Boardman
AU - David Quine
AU - Sabita Uthaya
AU - Shalini Ojha
AU - Hilary S Wong
AU - Annemarie Lodder
AU - Lauren Ingledow
AU - Peter Bradley
AU - James M S Wason
AU - John Norrie
AU - Ramon Luengo-Fernandez
AU - Andrew Morris
AU - Alex Baker
AU - Ricardo Ribas
AU - Daphne Babalis
AU - Neena Modi
PY - 2026
DA - 2026/10/06
JO - BMJ Open
DO - 10.1136/bmjopen-2026-125163
UR - https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2026-125163
AB - Introduction: Enteral feed type is widely believed to affect brain growth and development directly as well as influencing the risk of necrotising enterocolitis (NEC), a leading cause of death and neuro-impairment in extremely preterm babies. Own mother’s milk (OMM) enhances neurodevelopment and reduces NEC. However, most babies born below 29 weeks gestation require some supplementary feeds during their neonatal unit stay because their mothers are unable to express sufficient milk. The available options, pasteurised human donor milk (pHDM) and preterm formula (PTF), differ markedly in nutrient and non-nutrient composition and cost. Non-definitive data suggest superiority of pHDM over PTF in relation to NEC risk, but no benefits have been shown in important corroboratory outcomes: surgical NEC, death, blood stream infection and neurodevelopmental impairment. Human milk macronutrient content is variable and often low, hence some clinicians practise routine protein-carbohydrate fortification. Others fear that cow-milk derived fortifiers may increase NEC risk or may provide excessively high protein intakes dangerous to neurodevelopment and metabolic health. These uncertainties compromise patient care and safety and are strong justification for randomised evaluation. Methods and analysis: COLLABORATE is an efficient UK-wide, real-world data-enabled, 2-randomisation, group-sequential adaptive trial embedded in routine clinical practice. The primary outcome is survival to 34 weeks postmenstrual age without NEC surgery. The aim is to resolve two longstanding nutritional uncertainties for babies born below 29 weeks gestation: whether pHDM or PTF is the optimal supplement should there be an insufficiency of OMM; and whether OMM and pHDM require routine protein-carbohydrate fortification. Based on the assumption that 50% of participants will take part in both randomisations, total recruitment is targeted at 3252 (5% between-arm primary outcome difference; α=0.05; minimum 87% power). Ethics and dissemination: COLLABORATE is funded by the UK National Institute for Health and Care Research, sponsored by Imperial College London and approved by the UK Health Research Authority (reference 25/LO/0697). Recruitment commenced in April 2026. Results will be shared through academic and lay publications, conferences, workshops, social media and strong personal networks. Trial registration number: ISRCTN10443084 .
SN - 2044-6055
SN - 2044-6055
ER -