Early Use of Norepinephrine in Septic Shock Resuscitation (CENSER)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2013 by Mahidol University
Sponsor:
Collaborator:
Siriraj Hospital
Information provided by (Responsible Party):
Mahidol University
ClinicalTrials.gov Identifier:
NCT01945983
First received: September 16, 2013
Last updated: September 19, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention
Septic Shock
Severe Sepsis
Drug: Early norepinephrine
Drug: Placebo

Study Type: Interventional
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.

Resource links provided by NLM:


Further study details as provided by Mahidol University:

Primary Outcome Measures:
  • Therapeutic goal achievement [ Time Frame: 6 hours ] [ Designated as safety issue: Yes ]

    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:
  • Mortality rate [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]

Other Outcome Measures:
  • 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.


Estimated Enrollment: 300
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)
Arms Assigned Interventions
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.
Drug: Placebo
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.

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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01945983

Locations
Thailand
Siriraj Hospital Recruiting
Bangkok, Thailand, 10700
Contact: Chairat Permpikul, MD    0814081676    sicpk@mahidol.ac.th   
Contact: Tanuwong Viarasilpa, MD    0813469400    tanuwongviarasilpa@hotmail.com   
Principal Investigator: Chairat Permpikul, MD         
Sub-Investigator: Tanuwong Viarasilpa, MD         
Sub-Investigator: Surat Tongyoo, MD         
Sponsors and Collaborators
Mahidol University
Siriraj Hospital
Investigators
Principal Investigator: Chairat Permpikul, MD Mahidol University
  More Information

Publications:
Responsible Party: Mahidol University
ClinicalTrials.gov Identifier: NCT01945983     History of Changes
Other Study ID Numbers: Si507/2013
Study First Received: September 16, 2013
Last Updated: September 19, 2013
Health Authority: Thailand: Ethical Committee

Keywords provided by Mahidol University:
Septic shock
Severe sepsis
Norepinephrine

Additional relevant MeSH terms:
Shock, Septic
Sepsis
Toxemia
Shock
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Norepinephrine
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Vasoconstrictor Agents
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 20, 2014