NCT Number: NCT07343206
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
Interested in participating?
Request Info18 year and older
All sexes
Interventional
Not applicable
Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok Noi, Bangkok, Thailand
Healthy volunteers accepted: No
Only the study team can determine whether someone qualifies for participation.
Inclusion criteria
Exclusion criteria
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.
Placebo (D5W 250 mL) with an identical dosing schedule. Rescue norepinephrine available via a separate line. Same monitoring protocols.
Time frame: From enrollment to 28 days after enrollment
Survival at 28-day after enrollment. Telephone follow-up for patients who are discharged before 28 days.
Time frame: From enrollment to 6 hours after enrollment
Shock control defined as mean arterial pressure greater than 65 mmHg combined with urine output greater than 0.5 milliliters per kilogram per hour OR lactate clearance greater than 10 percent within 6 hours
Time frame: From enrollment to hospital discharge or 90 days (whichever comes first)
Days of intensive care unit stay
Time frame: From enrollment to hospital discharge or 90 days (whichever comes first)
Days of hospital stay
Time frame: From enrollment to hospital discharge or 90 days (whichever comes first)
Days on mechanical ventilation, including endotracheal tube and tracheostomy
Time frame: From enrollment to hospital discharge or 90 days (whichever comes first)
Days requiring renal replacement therapy, including continuous renal replacement therapy, intermittent hemodialysis, and peritoneal dialysis, that is newly initiated during this admission. Maintaining chronic hemodialysis is excluded.
Time frame: From enrollment to hospital discharge or 90 days (whichever comes first)
Days requiring vasopressor therapy
Time frame: From study drug initiation until achievement of all EGDT targets or up to 6 hours
Time in hours to achieve ALL EGDT targets: MAP ≥65 mmHg, urine output ≥0.5 mL/kg/hr, lactate clearance ≥10%, and ScvO₂ ≥70% (when measured)
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
Total volume in milliliters of intravenous crystalloid and colloid fluids administered during first 24 hours and first 72 hours Time Frame: At 1 hour, 6 hours, 24 hours (Day 1), 48 hours (Day 2), and 72 hours (Day 3) after treatment initiation
Time frame: From diagnosis until hospital discharge 90 days or death
New-onset cardiogenic pulmonary edema or non-cardiogenic pulmonary edema
Time frame: From study drug initiation until hospital discharge or death, assessed 90 days
Composite outcome including new-onset arrhythmias (AF, AFL, SVT, VT, VF, AV block, bradycardia), limb/mesenteric ischemia, skin necrosis, and severe hypertension
Contact information is provided by the study sponsor or research team.
Chairat Permpikul, Professor
CONTACT
Titaporn Nasaarn, Medical Doctor
CONTACT
Siriraj Hospital
Other
Efficacy of Early Norepinephrine Administration and Rapid Dose Adjustment in Adult Septic Shock Patients: A Multicenter Randomized Controlled Trial
Acronym: CENSER2
OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.
View the official ClinicalTrials.gov record (opens in a new tab)This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.
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