Early Norepinephrine Administration and Rapid Dose Adjustment

Официальное название

Efficacy of Early Norepinephrine Administration and Rapid Dose Adjustment in Adult Septic Shock Patients: A Multicenter Randomized Controlled Trial

Обзор

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

Вмешательства

• Препарат Early norepinephrine administration and rapid dose adjustment
  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.
• Препарат Control
  Placebo (D5W 250 mL) with an identical dosing schedule. Rescue norepinephrine available via a separate line. Same monitoring protocols.

Первичные конечные точки

• 28-day survival [Срок оценки: From enrollment to 28 days after enrollment]

Вторичные конечные точки (10)

• Number of participants with shock control achieved [Срок оценки: From enrollment to 6 hours after enrollment]
• Duration of intensive care unit stay [Срок оценки: From enrollment to hospital discharge or 90 days (whichever comes first)]
• Duration of hospital stay [Срок оценки: From enrollment to hospital discharge or 90 days (whichever comes first)]
• Duration of mechanical ventilation [Срок оценки: From enrollment to hospital discharge or 90 days (whichever comes first)]
• Duration of renal replacement therapy [Срок оценки: From enrollment to hospital discharge or 90 days (whichever comes first)]
• Duration of vasopressor therapy [Срок оценки: From enrollment to hospital discharge or 90 days (whichever comes first)]
• Time to Achievement of Early Goal-Directed Therapy Targets [Срок оценки: From study drug initiation until achievement of all EGDT targets or up to 6 hours]
• Cumulative Fluid Volume Administered [Срок оценки: 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 [Срок оценки: From diagnosis until hospital discharge 90 days or death]
• Treatment-Related Adverse Events Including Cardiac Arrhythmias [Срок оценки: From study drug initiation until hospital discharge or death, assessed 90 days]

Критерии участия

Критерии включения

• Age ≥ 18 years
• Sepsis: SOFA ≥2 with suspected infection
• Mean arterial pressure <65 mmHg
• Diagnosed within 3 hours

Критерии исключения

• 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

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Таиланд · 6 центров

• Faculty of Medicine Siriraj Hospital, Mahidol University — Bangkok Noi
• Kalasin Hospital — Kalasin
• Khon Kaen hospital — Khon Kaen
• Udon Thani Hospital — Udon Thani
• Hatyai Hospital — Hat Yai
• Maharaj Nakhon Si Thammarat Hospital — Nakhon Si Thammarat

Идентификаторы

NCT: NCT07343206 · Si 930/2025

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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