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

Официальное название

Dopamine vs. Norepinephrine for Hypotension in Very Preterm Infants With Late-onset Sepsis: An International Comparative Effectiveness Research Project

Обзор

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

Подробное описание

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.

Вмешательства

• Препарат 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.
• Препарат 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

Первичные конечные точки

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

Вторичные конечные точки (6)

• Episode-related death [Срок оценки: <14 days from illness onset]
• Treatment failure rate [Срок оценки: 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 [Срок оценки: From illness onset to discharge (home or to another hospital) - assessed up to a maximum of 36 weeks after date of birth]
• Bronchopulmonary dysplasia [Срок оценки: Assessed at 36 weeks PMA]
• Retinopathy of prematurity [Срок оценки: 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 [Срок оценки: From admission date to discharge date - assessed up to a maximum of 36 weeks after date of birth]

Критерии участия

Критерии включения

• ≤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)

Критерии исключения

• Known chromosomal or genetic anomalies
• Receiving primary therapy with agents other than Dopamine or Norepinephrine

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Канада · 16 центров

• 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
• … и ещё 8 центров

США · 3 центра

• Banner-University Medical Center Phoenix — Phoenix
• Dayton Children's Hospital — Dayton
• Methodist Healthcare — San Antonio

Ирландия · 2 центра

• University Cork College — Cork
• Coombe Women & Infants University Hospital — Dublin

Израиль · 1 центр

• Shamir Medical Center — Be’er Ya‘aqov

Испания · 1 центр

• La Paz University Hospital — Madrid

Идентификаторы

NCT: NCT05347238 · CTO 4009

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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