Emergency Department Management of Sepsis Patients: A Goal-Oriented Non-Invasive Sepsis Trial (AGONIST)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01453270
Recruitment Status : Completed
First Posted : October 17, 2011
Last Update Posted : September 25, 2014
Singapore Clinical Research Institute
Information provided by (Responsible Party):
National University Hospital, Singapore

Brief Summary:
The purpose of this study is to determine whether the use of a 3-hour protocol utilizing non-invasive hemodynamic optimization treatment strategy results in better outcome and lower hospital costs in patients who present with severe bloodstream infections to the Emergency Department (ED).

Condition or disease Intervention/treatment Phase
Sepsis Shock, Septic Device: NICOM Other: Usual care Not Applicable

Detailed Description:
Severe sepsis is a syndrome where the body develops organ dysfunction secondary to uncontrolled inflammatory response to infection. Various resuscitation bundles have been formulated and practised to treat severe sepsis, such as early goal-directed therapy (EGDT). EGDT involves the insertion of invasive catheters in patients with severe sepsis or septic shock using serial measurements to guide therapy and achieve hemodynamic goals, such as mean arterial pressure (MAP), central venous pressure (CVP) and central venous oxygen saturation (ScvO2) by 6 hours. The drawbacks include the invasive nature of inserting these catheters with its complications and tedium to set up the equipment. A non-invasive approach using the Non-Invasive Cardiac Output Monitor (NICOM) and passive leg raising (PLR) maneuver to guide fluid and vasoactive agent therapy targeting fluid responsiveness and MAP may be able to achieve better outcome, measured by lactate clearance at 3 hours and at a lower hospitalization cost.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 122 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Emergency Department Management of Sepsis Patients: A Goal-Oriented Non-Invasive Sepsis Trial
Study Start Date : November 2011
Actual Primary Completion Date : March 2014
Actual Study Completion Date : March 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sepsis

Arm Intervention/treatment
Experimental: NICOM and PLR
A systematic approach to resuscitation started in the ED and using a step-wise approach to optimize cardiac preload, afterload, and contractility, thus optimizing oxygen delivery to the tissues will be applied to the intervention group using the Non-Invasive Cardiac Output Monitor (NICOM) and passive leg-raising (PLR) maneuver.
Device: NICOM
Assessment of fluid responsiveness will be done using the non-invasive cardiac output monitor (NICOM) and passive leg-raising (PLR) maneuver to target mean arterial pressure of between 65mmHg and 90mmHg; and change in stroke volume index (SVI) less than 10%, prior to administration of fluid boluses.

Active Comparator: Usual care Other: Usual care
Usual care is given at the clinician's discretion in accordance with current best practice. Standard treatment may involve treatment with intravenous fluids, and medications to support the blood pressure and heart.

Primary Outcome Measures :
  1. Lactate clearance >20% [ Time Frame: 3 hours ]
    Arterial lactate levels will be measured at 0 and 3 hours to determine degree of lactate clearance at 3 hours.

Secondary Outcome Measures :
  1. Total hospital cost [ Time Frame: At discharge, death or 28 days, whichever occurs earlier ]

Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Fulfillment of at least 2 systemic inflammatory response syndrome (SIRS) criteria
  • Suspected infection
  • Serum lactate ≥3mmol/L

Exclusion Criteria:

  • Age below 21 years
  • Known pregnancy
  • Prisoners
  • Do-not-attempt resuscitation status
  • Known severe aortic insufficiency or severe anatomic abnormalities of the thoracic aorta
  • Primary diagnosis of trauma, burns, active seizures, acute cerebral vascular accident, acute coronary syndrome, status asthmaticus, major cardiac arrhythmias, active gastrointestinal haemorrhage, seizure or drug overdose
  • Requirement for immediate surgery
  • Inability to do PLR (e.g. ankylosis of hip joint, severe sciatica)
  • Treating physician deems aggressive care unsuitable
  • Those unable to give informed consent and unable to comply with study requirements

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01453270

National University Hospital
Singapore, Singapore, 119074
Sponsors and Collaborators
National University Hospital, Singapore
Singapore Clinical Research Institute
Principal Investigator: Win Sen Kuan, MBBS National University Health System, Singapore
Principal Investigator: Irwani Ibrahim, MBBS National University Health System, Singapore
Principal Investigator: Benjamin SH Leong, MBBS National University Health System, Singapore
Study Chair: Malcolm Mahadevan, MBBS National University Health System, Singapore
Principal Investigator: Yin Bun Cheung, PhD DUKE NUS Graduate Medical School Singapore

Responsible Party: National University Hospital, Singapore Identifier: NCT01453270     History of Changes
Other Study ID Numbers: AGONIST
First Posted: October 17, 2011    Key Record Dates
Last Update Posted: September 25, 2014
Last Verified: September 2014

Keywords provided by National University Hospital, Singapore:
Emergency medicine
Cardiac output
Stroke volume

Additional relevant MeSH terms:
Shock, Septic
Disease Attributes
Pathologic Processes
Systemic Inflammatory Response Syndrome