NCT05347238

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

Dopamine vs. Norepinephrine for Hypotension in Very Preterm Infants With Late-onset Sepsis: An International Comparative Effectiveness Research Project

• Status: Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 550 (estimated)
• Sponsor: Mount Sinai Hospital, Canada · Academic / Other
• Sex: All
• Age: 21 Weeks – 32 Weeks
• Healthy volunteers: Not accepted

Summary

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

Detailed description

In this study, we will use real world data (RWD; defined as data generated during routine clinical practice) collected by our national Canadian Neonatal Network (CNN), which will be further expanded for this project. The CNN is a well-established patient registry that includes members from 31 hospitals and 17 universities across Canada. The Network maintains a standardized NICU database and provides a unique opportunity for researchers to participate in collaborative projects. We will use the framework of Hypotheses Evaluating Treatment Effectiveness (HETE) research a form of comparative effectiveness research (CER). Patient registries are emerging as a new method for assessment of treatments under the framework of CER. We will evaluate treatment effectiveness of two routinely used primary therapies for hypotension management in very preterm neonates with suspected LOS after standardizing treatment strategies and with a priori hypothesis.

Conditions

• Late-Onset Neonatal Sepsis
• Extreme Prematurity
• Neonatal Hypotension

Interventions

Type	Name	Description
DRUG	Dopamine	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.
DRUG	Norepinephrine	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

Timeline

• Start date: 2023-02-06
• Primary completion: 2026-06-30
• Completion: 2027-03-31
• First posted: 2022-04-26
• Last updated: 2025-07-08

Locations

23 sites across 5 countries: United States, Canada, Ireland, Israel, Spain