Early Norepinephrine Administration and Rapid Dose Adjustment
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Early norepinephrine administration and rapid dose adjustment, Control.
- Who it may be relevant to
- Registry conditions: Sepsis, Septic Shock. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Thailand
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
Efficacy of Early Norepinephrine Administration and Rapid Dose Adjustment in Adult Septic Shock Patients: A Multicenter Randomized Controlled Trial
Overview
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
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.
Primary outcome measures
- 28-day survival [Time frame: From enrollment to 28 days after enrollment]
Secondary outcome measures (10)
- Number of participants with shock control achieved [Time frame: From enrollment to 6 hours after enrollment]
- Duration of intensive care unit stay [Time frame: From enrollment to hospital discharge or 90 days (whichever comes first)]
- Duration of hospital stay [Time frame: From enrollment to hospital discharge or 90 days (whichever comes first)]
- Duration of mechanical ventilation [Time frame: From enrollment to hospital discharge or 90 days (whichever comes first)]
- Duration of renal replacement therapy [Time frame: From enrollment to hospital discharge or 90 days (whichever comes first)]
- Duration of vasopressor therapy [Time frame: From enrollment to hospital discharge or 90 days (whichever comes first)]
- Time to Achievement of Early Goal-Directed Therapy Targets [Time frame: From study drug initiation until achievement of all EGDT targets or up to 6 hours]
- Cumulative Fluid Volume Administered [Time frame: 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 [Time frame: From diagnosis until hospital discharge 90 days or death]
- Treatment-Related Adverse Events Including Cardiac Arrhythmias [Time frame: From study drug initiation until hospital discharge or death, assessed 90 days]
Eligibility criteria
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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Quadruple blind
- Primary purpose
- Treatment
Study locations
Thailand · 6 centers
- 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
Identifiers
NCT: NCT07343206 · Si 930/2025