Early Norepinephrine Administration and Rapid Dose Adjustment (CENSER2)

April 21, 2026 updated by: Wasin Pansiritanachot, Siriraj Hospital

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

600

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Thailand
    • Bangkok
      • Bangkok Noi, Bangkok, Thailand, 10700
        • Recruiting
        • Faculty of Medicine Siriraj Hospital, Mahidol University
        • Contact:
        • Sub-Investigator:
          • Wasin Pansiritanachot, Medical Doctor
        • Principal Investigator:
          • Surat Tongyoo, Associate professor
    • Changwat Kalasin
      • Kalasin, Changwat Kalasin, Thailand, 46000
        • Recruiting
        • Kalasin Hospital
        • Contact:
        • Principal Investigator:
          • Suwimon Khansompop, Medical Doctor
    • Changwat Khon Kaen
      • Khon Kaen, Changwat Khon Kaen, Thailand, 4000
        • Recruiting
        • Khon Kaen hospital
        • Contact:
        • Principal Investigator:
          • Porntipa Tantibundit, Medical Doctor
    • Changwat Udon Thani
      • Udon Thani, Changwat Udon Thani, Thailand, 41000
        • Recruiting
        • Udon Thani Hospital
        • Contact:
        • Principal Investigator:
          • Anutr Thitayanapong, Medical Doctor
    • Hat Yai
      • Hat Yai, Hat Yai, Thailand, 90110
        • Recruiting
        • Hatyai Hospital
        • Contact:
        • Principal Investigator:
          • Suratee Chobngam, Medical Doctor
    • ์Nakhon Si Thammarat
      • Nakhon Si Thammarat, ์Nakhon Si Thammarat, Thailand, 8000
        • Recruiting
        • Maharaj Nakhon Si Thammarat Hospital
        • Contact:
        • Principal Investigator:
          • Katsakorn Kheawkaew, Medical Doctor

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Intervention

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
28-day survival
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.
From enrollment to 28 days after enrollment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of intensive care unit stay
Time Frame: From enrollment to hospital discharge or 90 days (whichever comes first)
Days of intensive care unit stay
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)
Days of hospital stay
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)
Days on mechanical ventilation, including endotracheal tube and tracheostomy
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)
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.
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)
Days requiring vasopressor therapy
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
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)
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
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
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
New-onset cardiogenic pulmonary edema or non-cardiogenic pulmonary edema
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
Composite outcome including new-onset arrhythmias (AF, AFL, SVT, VT, VF, AV block, bradycardia), limb/mesenteric ischemia, skin necrosis, and severe hypertension
From study drug initiation until hospital discharge or death, assessed 90 days
Number of participants with shock control achieved
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
From enrollment to 6 hours after enrollment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Siriraj Hospital

Collaborators

Khon Kaen Hospital
Udon Thani Regional Hospital
Kalasin Hospital
Maharaj Nakorn Si Thammarat
Hat Yai Hospital

Investigators

  • Principal Investigator: Chairat Permpikul, Professor, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2026

Primary Completion (Estimated)

January 1, 2028

Study Completion (Estimated)

March 1, 2028

Study Registration Dates

First Submitted

January 6, 2026

First Submitted That Met QC Criteria

January 6, 2026

First Posted (Actual)

January 15, 2026

Study Record Updates

Last Update Posted (Actual)

April 22, 2026

Last Update Submitted That Met QC Criteria

April 21, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Si 930/2025

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

De-identified anonymized patient data will be available upon reasonable request.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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