Early Norepinephrine Administration and Rapid Dose Adjustment (CENSER2)

Siriraj Hospital

Status: Not yet enrolling

Conditions: Septic Shock; Sepsis

Treatments: Drug: Early norepinephrine administration and rapid dose adjustment; Drug: Control

Study type: Interventional

Funder types: Other

Identifiers

NCT07343206

Si 930/2025

Details and patient eligibility

About

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

Enrollment: 600 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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600 participants in 2 patient groups

Intervention

Experimental group

Description:

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.

Treatment:

Drug: Early norepinephrine administration and rapid dose adjustment

Control

Sham Comparator group

Description:

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

Treatment:

Drug: Control