Early Norepinephrine Administration and Rapid Dose Adjustment

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

Conditions

• Sepsis
• Septic Shock

Interventions

DRUG

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.

DRUG

Control

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

Sponsors & Collaborators

• Maharaj Nakorn Si Thammarat

  collaborator UNKNOWN

• Kalasin Hospital

  collaborator OTHER

• Khon Kaen Hospital

  collaborator OTHER_GOV

• Udon Thani Regional Hospital

  collaborator UNKNOWN

• Hat Yai Hospital

  collaborator UNKNOWN

• Siriraj Hospital

  lead OTHER

Principal Investigators

• Chairat Permpikul, Professor · Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-01-01

Primary Completion

2028-01-31

Completion

2028-03-31

Countries

• Thailand

Study Locations