Dopamine vs. Norepinephrine for Hypotension in Very Preterm Infants With Late-onset Sepsis
1 other identifier
observational
550
5 countries
23
Brief 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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for all trials
Started Feb 2023
Longer than P75 for all trials
23 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 12, 2022
CompletedFirst Posted
Study publicly available on registry
April 26, 2022
CompletedStudy Start
First participant enrolled
February 6, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 30, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
March 31, 2027
July 8, 2025
July 1, 2025
3.4 years
April 12, 2022
July 3, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
All cause in-hospital mortality
Death before discharge
From illness onset to discharge (home or to another hospital) - assessed up to a maximum of 36 weeks after date of birth
Secondary Outcomes (6)
Episode-related death
<14 days from illness onset
Treatment failure rate
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
From illness onset to discharge (home or to another hospital) - assessed up to a maximum of 36 weeks after date of birth
Bronchopulmonary dysplasia
Assessed at 36 weeks PMA
Retinopathy of prematurity
From illness onset to discharge (home or to another hospital) - assessed up to a maximum of 36 weeks after date of birth
- +1 more secondary outcomes
Study Arms (2)
Dopamine Units
Units who have standardized their practice with the use of Dopamine as a first line agent.
Norepinephrine Units
Units who have standardized their practice with the use of Norepinephrine as a first line agent.
Interventions
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.
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
Eligibility Criteria
All preterm infants born ≤32 weeks gestational age and \> 48 hours of life with suspected sepsis with systemic hypotension admitted to the participating sites and meeting the above eligibility criteria will be included in the study.
You may qualify if:
- ≤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)
You may not qualify if:
- Known chromosomal or genetic anomalies
- Receiving primary therapy with agents other than Dopamine or Norepinephrine
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Mount Sinai Hospital, Canadalead
- Sunnybrook Health Sciences Centrecollaborator
- The Hospital for Sick Childrencollaborator
- London Health Sciences Centrecollaborator
- Windsor Regional Hospitalcollaborator
- Foothills Medical Centrecollaborator
- Health Sciences Centre, Winnipeg, Manitobacollaborator
- St. Boniface Hospitalcollaborator
- Jewish General Hospitalcollaborator
- St. Justine's Hospitalcollaborator
- IWK Health Centrecollaborator
- University College Corkcollaborator
- Coombe Women and Infants University Hospitalcollaborator
- Island Health, Victoria, BCcollaborator
- Assaf-Harofeh Medical Centercollaborator
- Dayton Children's Hospitalcollaborator
- Banner University Medical Centercollaborator
- Methodist Healthcarecollaborator
- Hospital Universitario La Pazcollaborator
- McMaster Children's Hospitalcollaborator
- Children's Hospital of Eastern Ontariocollaborator
- BC Women's Hospital & Health Centrecollaborator
- Stony Brook Universitycollaborator
- The Children's Hospital at Montefiorecollaborator
- Golisano Children's Hospitalcollaborator
Study Sites (23)
Banner-University Medical Center Phoenix
Phoenix, Arizona, 85006, United States
Dayton Children's Hospital
Dayton, Ohio, 45404, United States
Methodist Healthcare
San Antonio, Texas, 78229, United States
Foothill's Medical Centre
Calgary, Alberta, Canada
BC Women's Hospital
Vancouver, British Columbia, Canada
Victoria General Hospital
Victoria, British Columbia, V8Z 6R5, Canada
St.Boniface Hospital
Winnipeg, Manitoba, Canada
Winnipeg Health Sciences Centre
Winnipeg, Manitoba, Canada
IWK Health Centre
Halifax, Nova Scotia, Canada
McMaster Children's Hospital
Hamilton, Ontario, Canada
London Health Sciences Centre
London, Ontario, Canada
Children's Hospital of Eastern Ontario
Ottawa, Ontario, Canada
Hospital for Sick Children
Toronto, Ontario, Canada
Mount Sinai Hospital
Toronto, Ontario, Canada
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada
Windsor Regional Hospital
Windsor, Ontario, Canada
CHU Sainte- Justine
Montreal, Quebec, Canada
Jewish General Hospital
Montreal, Quebec, Canada
Montreal Children's Hospital
Montreal, Quebec, Canada
University Cork College
Cork, Ireland
Coombe Women & Infants University Hospital
Dublin, Ireland
Shamir Medical Center
Be’er Ya‘aqov, Israel
La Paz University Hospital
Madrid, 28046, Spain
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Amish Jain, MBBS, MRCPCH, PhD
Mount Sinai Hospital, Canada
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- COHORT
- Time Perspective
- PROSPECTIVE
- Target Duration
- 36 Weeks
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 12, 2022
First Posted
April 26, 2022
Study Start
February 6, 2023
Primary Completion (Estimated)
June 30, 2026
Study Completion (Estimated)
March 31, 2027
Last Updated
July 8, 2025
Record last verified: 2025-07
Data Sharing
- IPD Sharing
- Will not share