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

Conditions

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

Eligibility Criteria

Sex

ALL

Age

21 Weeks - 32 Weeks

Healthy Volunteers

Not accepted

Interventions

• Dopamine — DRUG
  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 — DRUG
  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

Study Details

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

Key Dates

Start date

Feb 6, 2023

Status verified

Jul 2025

Primary completion

Jun 30, 2026

Completion

Mar 31, 2027

Study Design

Enrollment

550 participants (estimated)

Arms

• Arm: Dopamine Units
  Units who have standardized their practice with the use of Dopamine as a first line agent.
• Arm: Norepinephrine Units
  Units who have standardized their practice with the use of Norepinephrine as a first line agent.

Primary Outcome Measure

All cause in-hospital mortality [ Time Frame: From illness onset to discharge (home or to another hospital) - assessed up to a maximum of 36 weeks after date of birth ]

Central Contacts

• Amish Jain, MBBS, MRCPCH, PhD
  416-586-4800
  [email protected]
• Laura Thomas, MSc
  416-586-4800
  [email protected]

Locations (3)

Find similar trials in Phoenix, AZ

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