Efficacy of Early Norepinephrine Administration and Rapid Dose Adjustment in Adult Septic Shock Patients: A Multicenter Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 600
- 试验地点
- 6
- 主要终点
- 28-day survival
研究概览
简要总结
The goal of this clinical trial is to determine whether early initiation of norepinephrine with rapid dose adjustment improves clinical outcomes in adult patients with septic shock. The study aims to evaluate the effect of early norepinephrine administration on mortality, hemodynamic stabilization, and resuscitation efficiency in adults aged 18 years and older diagnosed with septic shock.
The main questions it aims to answer are:
- Does early norepinephrine administration with rapid dose titration reduce 28-day mortality compared with standard treatment?
- Does early norepinephrine administration with rapid dose tiration lead to faster shock control and reduced fluid requirements without increasing treatment-related adverse events?
Researchers will compare early norepinephrine administration with rapid dose adjustment to placebo with standard sequential resuscitation and rescue norepinephrine as needed to see if early vasopressor initiation improves survival, shock resolution, and safety outcomes.
Participants will:
- Receive either norepinephrine or placebo infusion initiated within one hour of septic shock diagnosis, with dose adjustment every 15 minutes according to a standardized protocol
- Undergo close hemodynamic and safety monitoring, including frequent vital sign assessment and limb perfusion evaluation
- Receive standard sepsis care, including fluid resuscitation, antibiotics, and organ support as clinically indicated
- Be followed for clinical outcomes and adverse events for up to 28 days after enrollment
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years
- •Sepsis: SOFA ≥2 with suspected infection
- •Mean arterial pressure <65 mmHg
- •Diagnosed within 3 hours
排除标准
- •Do-not-resuscitate orders
- •Pregnancy
- •Severe concurrent conditions (acute stroke, acute coronary syndrome, acute pulmonary edema, status asthmaticus, active gastrointestinal bleeding, status epilepticus, severe burn, severe trauma, and fatal drug overdose, End-stage malignancy
- •Peripheral arterial disease
- •Prior norepinephrine administration
- •Recurrent shock in the same patient
研究组 & 干预措施
Intervention
Norepinephrine 4 mg in 250 mL D5W, initiated at 0.05 mcg/kg/min. Titrate by 0.025 mcg/kg/min every 15 minutes if MAP <65 mmHg, up to 0.15 mcg/kg/min maximum. Rescue norepinephrine available if needed (separate line). Limb ischemia monitoring every 15 minutes.
Duration: 24 hours.
干预措施: Early norepinephrine administration and rapid dose adjustment (Drug)
Control
Placebo (D5W 250 mL) with an identical dosing schedule. Rescue norepinephrine available via a separate line. Same monitoring protocols.
干预措施: Control (Drug)
结局指标
主要结局
28-day survival
时间窗: From enrollment to 28 days after enrollment
Survival at 28-day after enrollment. Telephone follow-up for patients who are discharged before 28 days.
次要结局
- Number of participants with shock control achieved(From enrollment to 6 hours after enrollment)
- Shock control(From enrollment to 6 hours after enrollment)
- Duration of intensive care unit stay(From enrollment to hospital discharge or 90 days (whichever comes first))
- Duration of hospital stay(From enrollment to hospital discharge or 90 days (whichever comes first))
- Duration of mechanical ventilation(From enrollment to hospital discharge or 90 days (whichever comes first))
- Duration of renal replacement therapy(From enrollment to hospital discharge or 90 days (whichever comes first))
- Duration of vasopressor therapy(From enrollment to hospital discharge or 90 days (whichever comes first))
- Time to Achievement of Early Goal-Directed Therapy Targets(From study drug initiation until achievement of all EGDT targets or up to 6 hours)
- Cumulative Fluid Volume Administered(Multiple assessments at: - Before randomization (baseline) - 1 hour after study drug initiation - 6 hours after study drug initiation - 24 hours (Day 1) 48 hours (Day 2) 72 hours (Day 3) after study drug initiation)
- Incidence of Pulmonary Edema(From diagnosis until hospital discharge 90 days or death)
- Treatment-Related Adverse Events Including Cardiac Arrhythmias(From study drug initiation until hospital discharge or death, assessed 90 days)
研究者
Wasin Pansiritanachot
Lecturer
Siriraj Hospital