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

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

Inclusion Criteria:

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

Exclusion Criteria:

• 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