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

NCT ID: NCT05347238

Last Updated: 2025-07-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

550 participants

Study Classification

OBSERVATIONAL

Study Start Date

2023-02-06

Study Completion Date

2027-03-31

Brief Summary

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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

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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

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Late-Onset Neonatal Sepsis Extreme Prematurity Neonatal Hypotension

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Dopamine Units

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

Dopamine

Intervention Type 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 Units

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

Norepinephrine

Intervention Type 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

Interventions

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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.

Intervention Type 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

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

21 Weeks

Maximum Eligible Age

32 Weeks

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sunnybrook Health Sciences Centre

OTHER

Sponsor Role collaborator

The Hospital for Sick Children

OTHER

Sponsor Role collaborator

London Health Sciences Centre

OTHER

Sponsor Role collaborator

Windsor Regional Hospital

OTHER

Sponsor Role collaborator

Foothills Medical Centre

OTHER

Sponsor Role collaborator

Health Sciences Centre, Winnipeg, Manitoba

OTHER

Sponsor Role collaborator

St. Boniface Hospital

OTHER

Sponsor Role collaborator

Jewish General Hospital

OTHER

Sponsor Role collaborator

St. Justine's Hospital

OTHER

Sponsor Role collaborator

IWK Health Centre

OTHER

Sponsor Role collaborator

University College Cork

OTHER

Sponsor Role collaborator

Coombe Women and Infants University Hospital

OTHER

Sponsor Role collaborator

Island Health, Victoria, BC

OTHER

Sponsor Role collaborator

Assaf-Harofeh Medical Center

OTHER_GOV

Sponsor Role collaborator

Dayton Children's Hospital

OTHER

Sponsor Role collaborator

Banner University Medical Center

OTHER

Sponsor Role collaborator

Methodist Healthcare

OTHER

Sponsor Role collaborator

Hospital Universitario La Paz

OTHER

Sponsor Role collaborator

McMaster Children's Hospital

OTHER

Sponsor Role collaborator

Children's Hospital of Eastern Ontario

OTHER

Sponsor Role collaborator

BC Women's Hospital & Health Centre

OTHER

Sponsor Role collaborator

Stony Brook University

OTHER

Sponsor Role collaborator

The Children's Hospital at Montefiore

OTHER

Sponsor Role collaborator

Golisano Children's Hospital

UNKNOWN

Sponsor Role collaborator

Mount Sinai Hospital, Canada

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Amish Jain, MBBS, MRCPCH, PhD

Role: PRINCIPAL_INVESTIGATOR

Mount Sinai Hospital, Canada

Locations

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Banner-University Medical Center Phoenix

Phoenix, Arizona, United States

Site Status NOT_YET_RECRUITING

Dayton Children's Hospital

Dayton, Ohio, United States

Site Status RECRUITING

Methodist Healthcare

San Antonio, Texas, United States

Site Status RECRUITING

Foothill's Medical Centre

Calgary, Alberta, Canada

Site Status RECRUITING

BC Women's Hospital

Vancouver, British Columbia, Canada

Site Status RECRUITING

Victoria General Hospital

Victoria, British Columbia, Canada

Site Status RECRUITING

St.Boniface Hospital

Winnipeg, Manitoba, Canada

Site Status NOT_YET_RECRUITING

Winnipeg Health Sciences Centre

Winnipeg, Manitoba, Canada

Site Status RECRUITING

IWK Health Centre

Halifax, Nova Scotia, Canada

Site Status RECRUITING

McMaster Children's Hospital

Hamilton, Ontario, Canada

Site Status RECRUITING

London Health Sciences Centre

London, Ontario, Canada

Site Status RECRUITING

Children's Hospital of Eastern Ontario

Ottawa, Ontario, Canada

Site Status RECRUITING

Hospital for Sick Children

Toronto, Ontario, Canada

Site Status RECRUITING

Mount Sinai Hospital

Toronto, Ontario, Canada

Site Status RECRUITING

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Site Status RECRUITING

Windsor Regional Hospital

Windsor, Ontario, Canada

Site Status RECRUITING

CHU Sainte- Justine

Montreal, Quebec, Canada

Site Status RECRUITING

Jewish General Hospital

Montreal, Quebec, Canada

Site Status RECRUITING

Montreal Children's Hospital

Montreal, Quebec, Canada

Site Status RECRUITING

University Cork College

Cork, , Ireland

Site Status RECRUITING

Coombe Women & Infants University Hospital

Dublin, , Ireland

Site Status NOT_YET_RECRUITING

Shamir Medical Center

Be’er Ya‘aqov, , Israel

Site Status RECRUITING

La Paz University Hospital

Madrid, , Spain

Site Status RECRUITING

Countries

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United States Canada Ireland Israel Spain

Central Contacts

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Amish Jain, MBBS, MRCPCH, PhD

Role: CONTACT

416-586-4800 ext. 5459

Laura Thomas, MSc

Role: CONTACT

416-586-4800 ext. 172060

Facility Contacts

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Suma Rao

Role: primary

Shreyas Arya

Role: primary

Melissa Althouse, MD

Role: primary

Amuchou Soraisham

Role: primary

Michael Castaldo

Role: primary

Thevanisha Pillay

Role: primary

Yasser ElSayed

Role: primary

Deepak Louis

Role: primary

Walid El Naggar

Role: primary

Amneet Sidhu

Role: primary

Soume Bhattacharya

Role: primary

Laurent Renesme

Role: primary

Bonny Jasani

Role: primary

Laura Thomas, MSc

Role: primary

Stephanie Fevrier, MSc

Role: primary

Sajit Augustine

Role: primary

Anie Lapointe

Role: primary

Nina Nouraeyan

Role: primary

Gabriel Altit

Role: primary

Eugene Dempsey

Role: primary

Jan Miletin

Role: primary

Sagee Nissimov

Role: primary

María Carmen Bravo, MD

Role: primary

Other Identifiers

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CTO 4009

Identifier Type: -

Identifier Source: org_study_id

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