The PROTECT-HIE Pilot Trial: Prophylactic Therapy to Enhance Cardiovascular Treatment in Neonatal Hypoxemic Ischemic Encephalopathy
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Feasibility/Safety
研究概览
简要总结
Some babies experience a lack of oxygen and blood flow around the time of birth. This can lead to a serious condition called hypoxic-ischemic encephalopathy (HIE), which can injure the brain and other organs, including the heart. To reduce brain injury, babies with HIE are treated with therapeutic hypothermia, a standard treatment in which the baby's body temperature is carefully lowered for several days. While cooling helps protect the brain, many babies with HIE still develop heart problems and low blood flow, which may worsen outcomes.
Doctors often use medications to support the heart and circulation in these babies, but there is no clear agreement on which medication works best or when it should be started. One commonly used medication is dobutamine, which helps the heart pump more effectively. Dobutamine is already used in newborn intensive care units when babies show signs of heart weakness, but it is usually started only after problems develop.
The PROTECT-HIE trial aims to find out whether it is possible and safe to start dobutamine early, before clear signs of heart failure appear, in newborns with HIE who are receiving therapeutic hypothermia. The idea is that early support of the heart may improve blood flow to vital organs, including the brain, and potentially reduce injury.
In this study, 40 newborns with HIE will take part at a single neonatal intensive care unit. Babies will be randomly assigned to one of two groups. One group will receive a low, preventative dose of dobutamine within the first four hours after cooling begins. The other group will receive a placebo (an inactive fluid that looks the same). Neither the families nor the medical team assessing outcomes will know which treatment the baby received.
The main goal of this study is to determine feasibility-that is, whether starting dobutamine early during cooling can be done reliably and safely in this setting. Researchers will also collect information on important health outcomes, such as signs of brain injury on MRI, seizures, need for additional heart medications, heart function on ultrasound, recovery of blood markers, urine output, length of hospital stay, and survival.
Because HIE is an emergency condition and treatment must start very soon after birth, parents will be approached for consent after the baby has been stabilized. This approach is commonly used in neonatal emergency research and has been approved in similar studies.
The results of this study will help determine whether a larger trial should be done in the future. Ultimately, this research aims to improve care and outcomes for babies affected by HIE by optimizing support for the heart during a critical period after birth.
详细描述
Purpose
The purpose of this study is to evaluate the feasibility and safety of initiating prophylactic dobutamine infusion in newborns with hypoxic-ischemic encephalopathy (HIE) who are undergoing therapeutic hypothermia (TH). Infants with HIE frequently experience cardiovascular instability during the early postnatal period, which may negatively affect cerebral perfusion and overall outcomes. This study aims to determine whether early, preventive cardiovascular support can be reliably implemented and whether it may be associated with improved short-term clinical outcomes.
Hypothesis
The primary hypothesis is that initiating prophylactic dobutamine infusion within the first four hours of therapeutic hypothermia in newborns with HIE is feasible and safe.
The secondary hypothesis is that early dobutamine prophylaxis may be associated with improved short-term in-hospital outcomes, including reduced severity of brain injury, improved cardiac function, and reduced need for escalation of cardiovascular support.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 1 Day 至 1 Day（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Newborns with hypoxemic ischemic encephalopathy (HIE) receiving therapeutic hypothermia (TH).
排除标准
- •Congenital abnormality
- •known contraindication of dobutamine
- •Left ventricular outflow tract dynamic obstruction
- •Hypersensitivity to dobutamine
- •Uncorrected tachyarrhythmias or ventricular fibrillation
- •Newborns who are already started on inotropes at the time of randomization.
- •Parental refusal to consent to participate
研究组 & 干预措施
Dobutamine group
If randomized to the prophylaxis/dobutamine arm, dobutamine will be administered at a dose of 10 mcg/kg/min via intravenous access within 4 hours of initiating TH. As a part of standard care for HIE, a central umbilical venous access is routinely acquired whenever possible. We will use the dobutamine concentration of 2000 mcg/ml. The infusion will be prepared in dextrose 5% solution in 50 mL bags. Dobutamine monograph is attached to the protocol as well (Appendix F). The infusion will be continued until either weaned by the clinical team, escalation of inotropic support, or improvement of clinical situation to allow weaning of dobutamine.
干预措施: Dobutamine (Drug)
Dobutamine group
If randomized to the prophylaxis/dobutamine arm, dobutamine will be administered at a dose of 10 mcg/kg/min via intravenous access within 4 hours of initiating TH. As a part of standard care for HIE, a central umbilical venous access is routinely acquired whenever possible. We will use the dobutamine concentration of 2000 mcg/ml. The infusion will be prepared in dextrose 5% solution in 50 mL bags. Dobutamine monograph is attached to the protocol as well (Appendix F). The infusion will be continued until either weaned by the clinical team, escalation of inotropic support, or improvement of clinical situation to allow weaning of dobutamine.
干预措施: TnECHO (Diagnostic Test)
Control group
Infants randomized to the placebo arm will receive an inert preparation containing no active pharmacologic agent. The placebo will be identical in appearance, volume, and method of administration to the active intervention and will be administered according to the same dosing schedule and duration. We will use dextrose 5% (as placebo), which will be started within 4 hours of initiating TH. The infusion will be continued until either weaned by the clinical team, escalation of inotropic support, or improvement of clinical situation to allow weaning of dobutamine.
干预措施: TnECHO (Diagnostic Test)
结局指标
主要结局
Feasibility/Safety
时间窗: At 24 hours of age
Proportion of eligible infants receiving the intervention (or placebo) within 4 hours of initiating TH
次要结局
- Brain injury(through study completion, an average of 1 month)
- Severity and type of brain injury(through study completion, an average of 1 month)
- Mortality(through study completion, an average of 1 month)
- Seizure activity(through study completion, an average of 1 month)
- Need for escalation the inotropic support(through study completion, an average of 1 month)
- TAPSE in mm(through study completion, an average of 1 month)
- RV FAC in %(through study completion, an average of 1 month)
- LV EF in %(through study completion, an average of 1 month)
- Urine output in cc/k/hour(through study completion, an average of 1 month)
- Length of hospital stay in days(through study completion, an average of 1 month)
- Time to normalizing lactate in hours(through study completion, an average of 1 month)
- Duration of inhaled nitric oxide in hours(through study completion, an average of 1 month)
研究者
Aimann Surak
Principal Investigator
University of Alberta