Early Use of Norepinephrine in Septic Shock Resuscitation

Not Applicable

Completed

• Conditions: Severe Sepsis; Septic Shock
• Interventions: Drug: Early norepinephrine; Drug: Placebo

• Registration Number: NCT01945983
• Lead Sponsor: Mahidol University

Brief Summary

Current septic shock guideline recommends fluid resuscitation as the first treatment. Vasopressors, including norepinephrine is recommended to start after achieve adequate fluid therapy. This can cause a certain duration of systemic hypotension before vasopressor is commenced. Initiation of norepinephrine together with fluid therapy soon after diagnosis of septic shock may increase blood pressure quicker than start treatment with intravenous fluid alone. The rapid restoration of perfusion pressure may improve septic shock outcome.

Detailed Description

We will include severe infection patient who had evidence of organ dysfunction and hypotension and randomize into 2 groups as following:

1. Control group. The patient will receive treatment according to septic shock guideline 2013, which start with intravenous fluid replacement until achieve target central venous pressure (CVP) or pulmonary capillary wedge pressure (PCWP) or other fluid responsive test goal. If the patient's mean arterial blood pressure still lower than 65 mmHg, then norepinephrine or dopamine will initiate to rise blood pressure. The patient will receive 5% dextrose water as the placebo of norepinephrine.

2. Early norepinephrine group. The patient will receive fluid therapy together with low dose of norepinephrine (0.05 mcg/kg/min). If after titrate intravenous fluid therapy until achieve goal CVP or PCWP or other fluid responsive test, but the mean blood pressure still lower than 65 mmHg, then additional titrate dose of norepinephrine will be given to the patient according to standard septic shock guideline.

Study Timeline

• Study First Submitted: 2013-09-16
• Study First Submitted QC: 2013-09-16
• Study First Posted: 2013-09-19
• Study Start: 2013-10-03
• Primary Completion: 2017-08
• Study Completion: 2017-08
• Status Verified: 2018-01
• Last Update Submitted: 2018-01-08
• Last Update Posted: 2018-01-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 310

Inclusion Criteria

• Age > or = 18 years old
• Diagnosed severe sepsis or septic shock according to survival sepsis campaign 2013
• Mean arterial pressure < 65 mmHg

Exclusion Criteria

• Pregnancy
• Severe underlying condition that unexpected to survive more than 48 hours
• Severe peripheral vascular disease
• Patient who required major surgery within 24 hours

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Early norepinephrine	Early norepinephrine	Norepinephrine 4 mg in 5% dextrose water 250 ml Intravenous infusion rate range from 8 to 15 ml/hour, adjusted according to patient's body weight to achieve norepinephrine 0.05microgram/kg/min Continuous drip for 48 hours.
Placebo	Placebo	5% dextrose water 250 ml Intravenous infusion rate range from 8 to 15 ml/hour. Adjust rate of infusion according to patient's body weight to achieve dosage of norepinephrine comparable to 0.05 microgram/kg/min Continuous drip for 48 hours.

Primary Outcome Measures

Name	Time	Method
Therapeutic goal achievement	6 hours	Therapeutic goal including; 1. Mean arterial blood pressure \> or = 65 mmHg; 2. Evidence of adequate tissue perfusion which include continuation of urine output \> or = 0.5 ml/kg/hour for 2 hours or decreasing of serum lactate \> or = 10 percent in 1 to 2 hours.

Secondary Outcome Measures

Name	Time	Method
Mortality rate	28 days

Trial Locations

Locations (1)

Siriraj Hospital; 🇹🇭 Bangkok, Thailand