Early Norepinephrine Administration and Rapid Dose Adjustment

NCT07343206 | Recruiting

• 1 other identifier: Si 930/2025
• Study Type: interventional
• Target: 600
• Locations: 1 country
• Sites: 6

Brief Summary

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

Conditions

Sepsis; Septic Shock

Keywords

septic shock; norepinephrine; sepsis; hypotension

Outcome Measures

Primary Outcomes (1)

• 28-day survival

  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 Outcomes (10)

• Number of participants with shock control achieved

  From enrollment to 6 hours after enrollment

• Duration of intensive care unit stay

  From enrollment to hospital discharge or 90 days (whichever comes first)

• Duration of hospital stay

  From enrollment to hospital discharge or 90 days (whichever comes first)

• Duration of mechanical ventilation

  From enrollment to hospital discharge or 90 days (whichever comes first)

• Duration of renal replacement therapy

  From enrollment to hospital discharge or 90 days (whichever comes first)

Study Arms (2)

Intervention

EXPERIMENTAL

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

Control

SHAM COMPARATOR

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

Drug: Control

Interventions

Early norepinephrine administration and rapid dose adjustment DRUG

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.

Intervention

Control DRUG

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

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Siriraj Hospital: lead
• Maharaj Nakorn Si Thammarat: collaborator
• Kalasin Hospital: collaborator
• Khon Kaen Hospital: collaborator
• Udon Thani Regional Hospital: collaborator
• Hat Yai Hospital: collaborator

Study Sites (6)

Faculty of Medicine Siriraj Hospital, Mahidol University

Bangkok Noi, Bangkok, 10700, Thailand

RECRUITING

Kalasin Hospital

Kalasin, Changwat Kalasin, 46000, Thailand

RECRUITING

Khon Kaen hospital

Khon Kaen, Changwat Khon Kaen, 4000, Thailand

RECRUITING

Udon Thani Hospital

Udon Thani, Changwat Udon Thani, 41000, Thailand

RECRUITING

Hatyai Hospital

Hat Yai, Hat Yai, 90110, Thailand

RECRUITING

Maharaj Nakhon Si Thammarat Hospital

Nakhon Si Thammarat, ์Nakhon Si Thammarat, 8000, Thailand

RECRUITING

MeSH Terms

Conditions

Sepsis; Shock, Septic; Hypotension

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Chairat Permpikul, Professor

  Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Titaporn Nasaarn, Medical Doctor

CONTACT

+66 82 429 5514; menatitaporn@gmail.com

Chairat Permpikul, Professor

CONTACT

+66 81 408 1676; chairat.per@mahidol.ac.th

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Lecturer

Study Record Dates

• First Submitted: January 6, 2026
• First Posted: January 15, 2026
• Study Start: January 1, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): March 1, 2028
• Last Updated: April 22, 2026

Record last verified: 2026-04

Locations

TH (6)