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

Sponsor

National University Hospital, Singapore (Other)

Overall Status

Completed

CT.gov ID

NCT01453270

Collaborator

Singapore Clinical Research Institute (Other)

122

Enrollment

Location

Arms

Duration (Months)

4.4

Patients Per Site Per Month

Study Details

Study Description

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	N/A

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 Design

Study Type:

Interventional

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 :

Nov 1, 2011

Actual Primary Completion Date :

Mar 1, 2014

Actual Study Completion Date :

Mar 1, 2014

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Lactate clearance >20% [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

Total hospital cost [At discharge, death or 28 days, whichever occurs earlier]

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National University Hospital	Singapore		Singapore	119074

Sponsors and Collaborators

National University Hospital, Singapore
Singapore Clinical Research Institute

Investigators

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