Intravenous Methylene Blue for Treating Fluid-refractory, Catecholamine-resistant, Neonatal Septic Shock: a Randomized, Placebo-controlled, Superiority Trial
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 130
- 试验地点
- 1
- 主要终点
- All-cause mortality within 7 days after randomization
研究概览
简要总结
Preterm infants (born at less than 37 weeks of pregnancy) sometimes develop a serious blood infection leading to low blood pressure, which does not respond to saline or to the standard medicines for increasing blood pressure, such as dopamine and epinephrine. The goal of this research study is to compare the effect of giving an injectable medicine called Methylene blue (MB) versus not giving MB to such preterm infants who are unresponsive to standard treatment. The main questions that this study aims to answer is:
- Whether MB treatment reduces death to any cause as compared to no MB treatment.
- Whether treatment with MB reduces the time to achieve normal blood pressure
- Whether treatment with MB reduces the time to stoppage of all blood pressure medications, steroids and normal saline.
- Whether treatment with MB improves heart function as measured by echocardiography at 24 and 48 hours.
详细描述
Preterm infants with definite or probable sepsis and fluid-refractory, catecholamine-resistant septic shock will be eligible for enrolment if they have no contraindication to receive MB. After obtaining parental consent, they will be stratified as per the first-line catecholamine used and randomly allocated to receive MB (bolus followed by infusion) or no MB for 24 hours. They will be observed for all-cause mortality (primary outcome), cause-specific mortality, time to achieve hemodynamic stability and adverse effects (secondary outcomes) over a 7-day period, all-cause mortality and cause-specific mortality hospital stay and duration of hospital stay.
The main questions it aims to answer are
- To determine whether treatment with intravenous MB therapy reduces all-cause mortality when compared to no MB treatment, among preterm neonates with catecholamine-resistant septic shock
- To compare the time to achieve therapeutic endpoints among preterm neonates with catecholamine-resistant septic shock treated with intravenous MB versus no MB
- To compare time to stoppage of all inotrope/vasopressor treatment among preterm neonates with catecholamine-resistant septic shock treated with intravenous MB versus no MB
- To compare echocardiographic parameters (at 24 hours after randomization) among preterm neonates with catecholamine-resistant septic shock treated with intravenous MB versus no MB
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Outcomes Assessor)
盲法说明
The random allocation will be concealed using serially numbered opaque sealed envelopes. After opening the envelope, a research nurse will administer a bolus of the study drug or placebo behind a screen, shielded from other staff. The infusion will be drawn up in an opaque syringe by the research nurse and infused through an intravenous tubing covered completely with aluminum foil. The research nurses will not be masked to the study drug. The parents of the subject, the regular staff nurses and doctors working in the unit and the project coordinator will be masked.
入排标准
- 年龄范围
- 0 Days 至 28 Days（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •excluded if ≥1 criterion positive:
- •G6PD deficient or family history of G6PD deficiency
- •Potentially lethal malformation
- •Congenital heart disease
- •Severe acute kidney injury
- •Family history of allergy to methylene blue or food dyes
研究组 & 干预措施
Methylene blue
Subjects in the intervention arm will receive a 1 mg/kg bolus of methylene blue over 30 minutes, followed by an infusion of 0.15 mg/kg/h. The infusion rate may be increased in steps of 0.15 mg/kg/h every 30 minutes until a maximum of 0.5 mg/kg/h.
干预措施: Methylene Blue (Drug)
Placebo infusion
Subjects in the control arm will receive a placebo infusion (normal saline) at the same volumetric rate.
干预措施: Placebo (Other)
结局指标
主要结局
All-cause mortality within 7 days after randomization
时间窗: 7 days
Mortality due to any cause over 7 days after randomization
次要结局
- Time taken to achieve therapeutic end-points within 7 days after randomization(7 days)
- Time taken to stop all inotrope/vasopressor treatment within 7 days after randomisation(7 days)
- Echocardiographic fractional shortening at 24 hour after randomization(24 hour)
- Septic shock-related mortality(7 days)
- Left ventricular end-systolic diameter (LVESD) by echocardiography at 24 hour after randomization(24 hour)
- Aortic diameter by echocardiography at 24 hour after randomization(24 hour)
- Mortality during hospital stay(100 days)
- Left ventricular end-diastolic diameter (LVEDD) by echocardiography at 24 hour after randomization(24 hour)
- Velocity time integral (LVI) by echocardiography at 24 hours after randomization(24 hour)
- Echocardiographic fractional shortening at 48 hour after randomization(48 hour)
- Left ventricular end-diastolic diameter (LVEDD) on echocardiography at 48 hour after randomization(48 hour)
- Aortic diameter by echocardiography at 48 hour after randomization(48 hour)
- Velocity time integral (LVI) by echocardiography at 48 hours after randomization(48 hour)
- Time taken to stop vasopressor treatment(100 days)
- Left ventricular end-systolic diameter (LVESD) by echocardiography at 48 hour after randomization(48 hour)
- Serious adverse effects(100 days)
研究者
Sourabh Dutta
Professor
Post Graduate Institute of Medical Education and Research, Chandigarh