Dopamine vs. Norepinephrine for Hypotension in Very Preterm Infants With Late-onset Sepsis: An International Comparative Effectiveness Research Project
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 550
- 试验地点
- 23
- 主要终点
- All cause in-hospital mortality
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 21 Weeks 至 32 Weeks（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≤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)
排除标准
- •Known chromosomal or genetic anomalies
- •Receiving primary therapy with agents other than Dopamine or Norepinephrine
研究组 & 干预措施
Dopamine Units
Units who have standardized their practice with the use of Dopamine as a first line agent.
干预措施: Dopamine (Drug)
Norepinephrine Units
Units who have standardized their practice with the use of Norepinephrine as a first line agent.
干预措施: Norepinephrine (Drug)
结局指标
主要结局
All cause in-hospital mortality
时间窗: From illness onset to discharge (home or to another hospital) - assessed up to a maximum of 36 weeks after date of birth
Death before discharge
次要结局
- Episode-related death(<14 days from illness onset)
- 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)
- Length of hospital stay(From admission date to discharge date - assessed up to a maximum of 36 weeks after date of birth)
- 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)
- Treatment failure rate(90 minutes after initial vasopressor initiation (or sooner if secondary dose added or primary agent replaced as per clinical discretion))