Dopamine vs. Norepinephrine for Hypotension in Very Preterm Infants With Late-onset Sepsis

Fluid-unresponsive hypotension needing cardiotropic drug treatment is a serious complication in very preterm neonates with suspected late-onset sepsis (LOS; defined as culture positive or negative bloodstream infection or necrotizing enterocolitis occurring \>48 hours of age). In Canada, \~250 very preterm neonates receive cardiotropic drugs for LOS related fluid-unresponsive hypotension every year; of these \~35-40% die. Unlike for adult patients, there is little evidence to inform practice. While several medications are used by clinicians, the most frequently used medications are Dopamine (DA) and Norepinephrine (NE). However, their relative impact on patient outcomes and safety is not known resulting in significant uncertainty and inter- and intra-unit variability in practice. Conducting large randomized trials in this subpopulation can be operationally challenging and expensive. Comparative effectiveness research (CER), is a feasible alternative which can generate high-quality real-world evidence using real-world data, by comparing the impact of different clinical practices. Aim: To conduct an international CER study, using a pragmatic clinical trial design, in conjunction with the existing infrastructure of the Canadian Neonatal Network to identify the optimal management of hypotension in very preterm neonates with suspected LOS. Objective: To compare the relative effectiveness and safety of pharmacologically equivalent dosages of DA versus NE for primary pharmacotherapy for fluid-unresponsive hypotension in preterm infants born ≤ 32 weeks gestational age with suspected LOS. Hypothesis: Primary treatment with NE will be associated with a lower mortality Methods: This CER project will compare management approach at the unit-level allowing inclusion of all eligible patients admitted during the study period. 16 centers in Canada, 2 centers in Ireland, 1 center in each of Israel, Spain and the UK, and 6 centers in the United States have agreed to standardize their practice. All eligible patients deemed circulatory insufficient will receive fluid therapy (minimum 10-20 cc/kg). If hypotension remains unresolved: Dopamine Units: start at 5mics/kg/min, increase every 16-30 minutes by 5 mics/kg/min to a maximum dose of 15 mics/kg/min or adequate response Norepinephrine Units: start at 0.05 mics/kg/min, increase every 16-30 minutes by 0.05 mics/kg/min to maximum dose of 0.15/mics/kg/min or adequate response

NCT Number	NCT05347238
Lead Sponsor	Mount Sinai Hospital, Canada Collaborators: Sunnybrook Health Sciences Centre, The Hospital for Sick Children, London Health Sciences Centre, Windsor Regional Hospital, Foothills Medical Centre, Health Sciences Centre, Winnipeg, Manitoba, St. Boniface Hospital, Jewish General Hospital, St. Justine's Hospital, IWK Health Centre, University College Cork, Coombe Women and Infants University Hospital, Island Health, Victoria, BC, Assaf-Harofeh Medical Center, Dayton Children's Hospital, Banner University Medical Center, Methodist Healthcare - Memphis, Hospital Universitario La Paz, McMaster Children's Hospital, Children's Hospital of Eastern Ontario, BC Women's Hospital & Health Centre, Stony Brook University, Children's Hospital at Montefiore, Golisano Children's Hospital
Conditions	Late-Onset Neonatal Sepsis, Extreme Prematurity, Neonatal Hypotension
Enrollment	550 participants
Start Date	2023-02-06
Primary Completion	2026-06-30 (estimated)
Study Completion	2027-03-31 (estimated)
Updated on ClinicalTrials.gov	2025-07-08