Early Use of Norepinephrine in Septic Shock Resuscitation (CENSER)

Mahidol University

Status: Completed

Conditions: Severe Sepsis; Septic Shock

Treatments: Drug: Placebo; Drug: Early norepinephrine

Study type: Interventional

Funder types: Other

Identifiers

NCT01945983

Si507/2013

Details and patient eligibility

About

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.

Full 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.

Enrollment: 310 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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310 participants in 2 patient groups, including a placebo group

Early norepinephrine

Active Comparator group

Description:

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.

Treatment:

Drug: Early norepinephrine

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo