Early Use of Norepinephrine in Septic Shock Resuscitation (CENSER)
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||The Comparison Between Early Norepinephrine Use and Standard Treatment During Severe Sepsis and Septic Shock Resuscitation.|
- Therapeutic goal achievement [ Time Frame: 6 hours ] [ Designated as safety issue: Yes ]
Therapeutic goal including
- Mean arterial blood pressure > or = 65 mmHg
- 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.
- Mortality rate [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
- Survive with organ support free days [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]The days that patient can survive without vasopressor, ventilator support and renal replacement therapy.
|Study Start Date:||September 2013|
|Estimated Study Completion Date:||August 2017|
|Estimated Primary Completion Date:||August 2017 (Final data collection date for primary outcome measure)|
Active Comparator: 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.
Drug: Early norepinephrine
Initiation of norepinephrine, a strong vasoconstrictor, at the initiation of septic shock management, together with fluid resuscitation.
Other Name: Early vasopressor therapy
Placebo Comparator: 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.
5% dextrose water intravenous drip in the same rate of calculated norepinephrine for the patient's body weight
Other Name: 5%D/W infusion as the placebo of norepinephrine.
We will include severe infection patient who had evidence of organ dysfunction and hypotension and randomize into 2 groups as following:
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01945983
|Bangkok, Thailand, 10700|
|Contact: Chairat Permpikul, MD 0814081676 firstname.lastname@example.org|
|Contact: Tanuwong Viarasilpa, MD 0813469400 email@example.com|
|Principal Investigator: Chairat Permpikul, MD|
|Sub-Investigator: Tanuwong Viarasilpa, MD|
|Sub-Investigator: Surat Tongyoo, MD|
|Principal Investigator:||Chairat Permpikul, MD||Mahidol University|