RecruitingNot ApplicableNCT07343206

Early Norepinephrine Administration and Rapid Dose Adjustment

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


Sponsor

Siriraj Hospital

Enrollment

600 participants

Start Date

Jan 1, 2026

Study Type

INTERVENTIONAL

Conditions

Summary

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


Eligibility

Min Age: 18 Years

Inclusion Criteria4

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

Exclusion Criteria6

  • 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

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Interventions

DRUGEarly 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.

DRUGControl

Placebo (D5W 250 mL) with an identical dosing schedule. Rescue norepinephrine available via a separate line. Same monitoring protocols.


Locations(6)

Faculty of Medicine Siriraj Hospital, Mahidol University

Bangkok Noi, Bangkok, Thailand

Kalasin Hospital

Kalasin, Changwat Kalasin, Thailand

Khon Kaen hospital

Khon Kaen, Changwat Khon Kaen, Thailand

Udon Thani Hospital

Udon Thani, Changwat Udon Thani, Thailand

Hatyai Hospital

Hat Yai, Hat Yai, Thailand

Maharaj Nakhon Si Thammarat Hospital

Nakhon Si Thammarat, ์Nakhon Si Thammarat, Thailand

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NCT07343206


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