Late-Onset Neonatal SepsisNCT05347238
Dopamine vs. Norepinephrine for Hypotension in Very Preterm Infants With Late-onset Sepsis
An observational study of Late-Onset Neonatal Sepsis and Extreme Prematurity, run by Mount Sinai Hospital, Canada at 22 sites in 5 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 21 to 32 weeks
- Conditions the study is for
- Late-Onset Neonatal Sepsis, Extreme Prematurity, Neonatal Hypotension
- What is being tested?
- Dopamine and Norepinephrine
- How many people
- 550 participants
- Where
- 22 sitesin 5 countries
- Study dates
- 6 Feb 2023to 31 Mar 2028
- How long will I take part?
- 36 Weeks
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 32 weeks
- All sexes
- No healthy volunteers
- Child
Study population: 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.
Who may be able to join
- ≤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)
Who cannot join
- Known chromosomal or genetic anomalies
- Receiving primary therapy with agents other than Dopamine or Norepinephrine
Trial locations and contacts
22 sites in 5 countries. Contact the study team or a site near you to ask about taking part.
22 sites in 5 countries
Canada16 sites, 16 recruiting
- Recruiting
Foothill's Medical Centre
Calgary, Alberta
Amuchou Soraisham
Amuchou Soraisham
- Recruiting
IWK Health Centre
Halifax, Nova Scotia
Walid El Naggar
Walid El Naggar
- Recruiting
McMaster Children's Hospital
Hamilton, Ontario
Amneet Sidhu
Amneet Sidhu
- Recruiting
London Health Sciences Centre
London, Ontario
Soume Bhattacharya
Soume Bhattacharya
- Recruiting
CHU Sainte- Justine
Montreal, Quebec
Anie Lapointe
Anie Lapointe
- Recruiting
Jewish General Hospital
Montreal, Quebec
Nina Nouraeyan
Nina Nouraeyan
- Recruiting
Montreal Children's Hospital
Montreal, Quebec
Gabriel Altit
Gabriel Altit
- Recruiting
Children's Hospital of Eastern Ontario
Ottawa, Ontario
Laurent Renesme
Laurent Renesme
- Recruiting
Hospital for Sick Children
Toronto, Ontario
Bonny Jasani
Bonny Jasani
- Recruiting
Mount Sinai Hospital
Toronto, Ontario
Laura Thomas, MSc, laura.thomas@sinaihealth.ca
Amish Jain
- Recruiting
Sunnybrook Health Sciences Centre
Toronto, Ontario
Dany Weisz, MD, dany.weisz@sunnybrook.ca
Dany Weisz
- Recruiting
BC Women's Hospital
Vancouver, British Columbia
Michael Castaldo
Michael Castaldo
- Recruiting
Victoria General Hospital
Victoria, British Columbia, V8Z 6R5
Thevanisha Pillay, Thevanisha.Pillay@islandhealth.ca
- Recruiting
Windsor Regional Hospital
Windsor, Ontario
Sajit Augustine
Sajit Augustine
- Not yet recruiting
St.Boniface Hospital
Winnipeg, Manitoba
Yasser ElSayed
Yasser ElSayed
- Recruiting
Winnipeg Health Sciences Centre
Winnipeg, Manitoba
Deepak Louis
Deepak Louis
United States3 sites, 3 recruiting
- Recruiting
Dayton Children's Hospital
Dayton, Ohio, 45404
Shreyas Arya
- Not yet recruiting
Banner-University Medical Center Phoenix
Phoenix, Arizona, 85006
Suma Rao
- Recruiting
Methodist Healthcare
San Antonio, Texas, 78229
Melissa Althouse, MD
Ireland1 site, 1 recruiting
- Recruiting
University Cork College
Cork
Eugene Dempsey
Israel1 site, 1 recruiting
- Recruiting
Shamir Medical Center
Be’er Ya‘aqov
Sagee Nissimov
Sagee Nissimov, MD
Spain1 site, 1 recruiting
- Recruiting
La Paz University Hospital
Madrid, 28046
María Carmen Bravo, MD, mcarmen.bravo@salud.madrid.org
About this study
Official title: Dopamine vs. Norepinephrine for Hypotension in Very Preterm Infants With Late-onset Sepsis: An International Comparative Effectiveness Research Project
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.
Read more
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
Read the 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.
- Being tested
- Dopamine, Norepinephrine
- Medical subject headings
- Neonatal Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DopamineDrug
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.
NorepinephrineDrug
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 group | Role | What they receive |
|---|---|---|
| Dopamine Units | Units who have standardized their practice with the use of Dopamine as a first line agent. Receives: Drug: Dopamine | |
| Norepinephrine Units | Units who have standardized their practice with the use of Norepinephrine as a first line agent. Receives: Drug: Norepinephrine |
What is being measured
The primary outcome is the main question the study is designed to answer.
All cause in-hospital mortality
Death before discharge
Measured: 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
Episode-related death (yes or no- binary variable)
Measured: <14 days from illness onset
Treatment failure rate
Need for further dose escalation or use of additional agents (treatment failure = hypotension unresolved after reaching max dose (15mics/kg/min in Dopamine units and 0.15 mics/kg/min in Norepinephrine units)
Measured: 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
Grade III or Grade IV intraventricular hemorrhage or periventricular leukomalacia (yes or no- binary variable)
Measured: From illness onset to discharge (home or to another hospital) - assessed up to a maximum of 36 weeks after date of birth
Bronchopulmonary dysplasia
Need for oxygen or positive pressure respiratory support at 36 weeks postmenstrual age (PMA) (yes or no- binary variable)
Measured: Assessed at 36 weeks PMA
Retinopathy of prematurity
Diagnosis of retinopathy of prematurity - assessed by clinical staff (yes or no - binary variable)
Measured: 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
Length of entire neonatal intensive care unit stay from admission to discharge
Measured: From admission date to discharge date - assessed up to a maximum of 36 weeks after date of birth
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2022
- Study start6 Feb 2023
- Primary completion30 Jun 2027 (estimated)
- Study completion31 Mar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Late-Onset Neonatal SepsisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 550 participants (estimated)
- Target duration
- 36 Weeks
Sponsor and investigators
- Lead sponsor
- Mount Sinai Hospital, Canada
- Sponsor type
- University, hospital or other
- 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, 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
- Responsible party
- Sponsor
- Investigators
- Amish Jain, MBBS, MRCPCH, PhD, Principal investigator, Mount Sinai Hospital, Canada
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05347238
- Sponsor's protocol ID
- CTO 4009
- Status last verified
- Oct 2026
- First submitted
- 12 Apr 2022
- Last updated
- 16 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No