Dopamine vs. Norepinephrine for Hypotension in Very Preterm Infants With Late-onset Sepsis
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Dopamine, Norepinephrine.
- Who it may be relevant to
- Registry conditions: Late-Onset Neonatal Sepsis, Extreme Prematurity, Neonatal Hypotension. Basic parameters: 21 Weeks — 32 Weeks · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States, Canada, Ireland, Israel, Spain
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
Dopamine vs. Norepinephrine for Hypotension in Very Preterm Infants With Late-onset Sepsis: An International Comparative Effectiveness Research Project
Overview
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.
Interventions
- 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
Primary outcome measures
- 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]
Secondary outcome measures (6)
- Episode-related death [Time frame: <14 days from illness onset]
- Treatment failure rate [Time frame: 90 minutes after initial vasopressor initiation (or sooner if secondary dose added or primary agent replaced as per clinical discretion)]
- New diagnosis of severe neurological injury [Time frame: From illness onset to discharge (home or to another hospital) - assessed up to a maximum of 36 weeks after date of birth]
- Bronchopulmonary dysplasia [Time frame: Assessed at 36 weeks PMA]
- Retinopathy of prematurity [Time frame: From illness onset to discharge (home or to another hospital) - assessed up to a maximum of 36 weeks after date of birth]
- Length of hospital stay [Time frame: From admission date to discharge date - assessed up to a maximum of 36 weeks after date of birth]
Eligibility criteria
Inclusion criteria
- ≤32 weeks gestational age and > 48 hours of life
- Receiving primary vasopressor therapy with Dopamine or Norepinephrine in the context of suspected late-onset sepsis or necrotizing enterocolitis with systemic hypotension (defined as: culture positive or negative bloodstream infection)
Exclusion criteria
- Known chromosomal or genetic anomalies
- Receiving primary therapy with agents other than Dopamine or Norepinephrine
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Observational model
- Cohort
Study locations
Canada · 16 centers
- Foothill's Medical Centre — Calgary
- BC Women's Hospital — Vancouver
- Victoria General Hospital — Victoria
- St.Boniface Hospital — Winnipeg
- Winnipeg Health Sciences Centre — Winnipeg
- IWK Health Centre — Halifax
- McMaster Children's Hospital — Hamilton
- London Health Sciences Centre — London
- … and 8 more centers
United States · 3 centers
- Banner-University Medical Center Phoenix — Phoenix
- Dayton Children's Hospital — Dayton
- Methodist Healthcare — San Antonio
Ireland · 2 centers
- University Cork College — Cork
- Coombe Women & Infants University Hospital — Dublin
Israel · 1 center
- Shamir Medical Center — Be’er Ya‘aqov
Spain · 1 center
- La Paz University Hospital — Madrid
Identifiers
NCT: NCT05347238 · CTO 4009