Giving norepinephrine early and adjusting the dose quickly for adults with septic shock

Efficacy of Early Norepinephrine Administration and Rapid Dose Adjustment in Adult Septic Shock Patients: A Multicenter Randomized Controlled Trial

This trial will test whether starting norepinephrine early and rapidly titrating the dose helps adults with septic shock survive and recover faster.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 600 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Siriraj Hospital (Academic / other)
• Locations: 6 sites (Bangkok Noi, Bangkok and 5 other locations)
• Trial ID: NCT07343206 on ClinicalTrials.gov

What this trial studies

Adults with septic shock diagnosed within three hours (SOFA ≥2 and MAP <65 mmHg) are randomized to receive either early norepinephrine with rapid dose adjustment or placebo with standard sequential resuscitation and rescue norepinephrine as needed. The protocol emphasizes immediate vasopressor initiation and fast titration to achieve hemodynamic targets while tracking fluid use and adverse events. Primary outcomes include 28-day mortality, time to shock control, and total fluid requirements, with safety monitoring for treatment-related harms. Participating sites are tertiary and regional hospitals in Thailand where enrolled patients are treated in the acute care setting.

Who should consider this trial

Good fit: Adults aged 18 or older with suspected infection, SOFA ≥2, mean arterial pressure under 65 mmHg, and diagnosed within three hours who have not already received norepinephrine are the intended participants.

Not a fit: Patients with do-not-resuscitate orders, pregnancy, prior norepinephrine, severe concurrent acute conditions (for example acute stroke, acute coronary syndrome, pulmonary edema, major trauma, active GI bleeding), end-stage malignancy, peripheral arterial disease, or recurrent shock are excluded and unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could lower deaths from septic shock, speed shock resolution, and reduce the amount of IV fluid patients need.

How similar studies have performed: Smaller randomized trials and observational studies have suggested early norepinephrine can speed shock control and reduce fluids, but a clear, consistent mortality benefit has not yet been established.

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

Where this trial is running

Bangkok Noi, Bangkok and 5 other locations

• Faculty of Medicine Siriraj Hospital, Mahidol University — Bangkok Noi, Bangkok, Thailand (Recruiting)
• Kalasin Hospital — Kalasin, Changwat Kalasin, Thailand (Recruiting)
• Khon Kaen hospital — Khon Kaen, Changwat Khon Kaen, Thailand (Recruiting)
• Udon Thani Hospital — Udon Thani, Changwat Udon Thani, Thailand (Recruiting)
• Hatyai Hospital — Hat Yai, Hat Yai, Thailand (Recruiting)
• Maharaj Nakhon Si Thammarat Hospital — Nakhon Si Thammarat, ์Nakhon Si Thammarat, Thailand (Recruiting)

Study contacts

• Principal investigator: Chairat Permpikul, Professor — Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University
• Study coordinator: Titaporn Nasaarn, Medical Doctor

Conditions Sepsis; Septic Shock; septic shock; norepinephrine; sepsis; hypotension