Early Goal-Directed Sedation Compared With Standard Care in Mechanically Ventilated Critically Ill Patients (SPICE III RCT)
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|ClinicalTrials.gov Identifier: NCT01728558|
Recruitment Status : Completed
First Posted : November 20, 2012
Last Update Posted : August 20, 2019
The Use of sedative drugs in intensive care is widespread. A cohort study conducted in Australia and New Zealand in 2010 revealed a high prevalence of deep sedation within the first 48 hours of mechanical ventilation which was independently linked to prolonged ventilation, hospital and 180 days mortality. Clinical practice is moving towards the use of lighter levels of sedation. Recent RCTs in Europe (JAMA 2012) and previous RCTs (JAMA 2009) supports growing evidence that dexmedetomidine facilitates rousable sedation, shortens ventilation time and attenuates delirium when compared to midazolam and propofol.
The investigators confirmed in a pilot study the feasibility, efficacy and safety of a process of care known as Early Goal Directed Sedation (EGDS) that delivers:
- Early randomization after intubation or arrival in the ICU (intubated).
- Early Adequate analgesia after randomization.
- Goal directed sedation titrated to achieve light sedation.
- Dexmedetomidine based algorithm as the primary sedative agent with avoidance of benzodiazepines.
The aim of this study is to assess the effectiveness of Early Goal Directed Sedation when compared to standard care sedation in critically ill patients.
The study hypothesis is that Early Goal-Directed Sedation (EGDS), compared to standard care sedation, reduces 90-day all-cause mortality in critically ill patients who require mechanical ventilation.
|Condition or disease||Intervention/treatment||Phase|
|Critical Illness and Mechanical Ventilation||Other: Early goal Directed Sedation Other: Standard care sedation||Phase 3|
This is a large-scale study into the effectiveness of a novel approach for sedation in ventilated critically ill patients. The primary aim of this study is to determine whether Early Goal Directed Sedation therapy, compared to standard care sedation, reduces 90-day mortality in critically ill patients ventilated > 24 hrs.
The study will be a randomized, unblinded, controlled trial conducted in approximately 35-50 intensive care units (ICUs) and will recruit 4000 mechanically ventilated patients (life support) who are expected to remain on the ventilator > 24 hours AND require immediate ongoing sedative medication for comfort, safety, and to facilitate the delivery of life support measures, including mechanical ventilation.
Patients with primary brain injury or prolonged weakness are excluded. Participants will be randomized into one of 2 study groups. All patients will receive adequate analgesia at randomization at the discretion of treating clinician. All randomized patients will have Light sedation as the default target unless otherwise clinically indicated. The intervention group will receive EGDS with dexmedetomidine as the primary sedative agent to achieve light sedation, with the addition of propofol as required. The use of benzodiazepines in the intervention group is not allowed, with the exception of specific, defined circumstances.
The control group will have sedation according to usual practice as chosen by the treating clinician. The use of dexmedetomidine is not allowed, with the exception of specific, defined circumstances.
Deidentified data will be collected and will include; Baseline demographic information; Doses of all sedative, analgesic and other related medications; Pain, sedation and delirium scores and major treatments such as ventilation time, tracheostomy and dialysis. Patients surviving to hospital discharge will be contacted by phone to determine independent survival status at 90 days and again at 180 days plus Health Related Quality of Life and cognitive function assessment.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||4000 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Early Goal-Directed Sedation Compared With Standard Care in Mechanically Ventilated Critically Ill Patients: a Prospective Multicentre Randomised Controlled Trial|
|Actual Study Start Date :||November 2013|
|Actual Primary Completion Date :||August 2018|
|Actual Study Completion Date :||December 2018|
Early Goal Directed Sedation
Early Goal Directed Sedation process of care involves:
Dexmedetomidine infusion will be continued until sedation is no longer clinically indicated up to a maximum of 28 days after enrolment.
Other: Early goal Directed Sedation
Active Comparator: Standard care Sedation Arm
Patients randomised to the standard care sedation arm will receive process of care sedation directed by the treating clinician. Based on the information from our observational study and the EGDS Pilot trial, most patients in this group are likely to receive midazolam and /or propofol. These agents will be infused to achieve the default target of Light sedation (RASS -2 to +1) whenever clinically appropriate and as specified by the treating clinician. The use remifentanil or dexmedetomidine for initial and maintenance sedation will be precluded.
Other: Standard care sedation
- Mortality [ Time Frame: Day 90 post randomisation ]
- Ventilation free days [ Time Frame: at 28 days following randomisation ]
- Proportion of RASS measurements in target range [ Time Frame: up to day 28 ]
- Incidence and duration of delirium measured by delirium free days [ Time Frame: up to 28 days ]
- Length of ICU stay [ Time Frame: up to 180 days ]
- Proportion of patients who receive a tracheostomy Proportion of patients who require: re-intubation, physical restraints,or unplanned extubation, [ Time Frame: up to day 28 ]
- Cumulative dose of midazolam, propofol, dexmedetomidine, fentanyl, and morphine [ Time Frame: up to 28 days ]
- Duration of treatment with midazolam, propofol, dexmedetomidine, fentanyl, and morphine [ Time Frame: up to 28 days ]
- Mortality at hospital discharge [ Time Frame: at hospital discharge up to 180 days ]
- Length of hospital stay [ Time Frame: up to 180 days ]
- Readmission to ICU [ Time Frame: at 90 days ]
- EQ-5D questionnaire [ Time Frame: at 180 days ]
- Cognitive function [ Time Frame: at 180 days ]
- Mortality at ICU discharge [ Time Frame: up to 180 days ]
- Full time institutional dependency at 180 days [ Time Frame: up to 180 days ]
- Discharge destination [ Time Frame: up to 180 days ]
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 ClinicalTrials.gov identifier (NCT number): NCT01728558
|Study Chair:||Yahya Shehabi, MD, FCICM, FANZCA, EMBA||University New South Wales, Prince of Wales Hospital, ANZIC-RC|
|Principal Investigator:||Rinaldo Bellomo||ANZIC-RC & Austin Hospital|
|Principal Investigator:||Steve A. R Webb||ANZIC-RC & Royal Perth Hospital|
|Principal Investigator:||Michael C Reade||ANZIC-RC, Royal Brisbane & Women's Hospital, Department of Military Medicine and Surgery,|
|Principal Investigator:||Belinda D Howe||ANZIC-RC|
|Principal Investigator:||Ian M Seppelt||ANZIC-RC, Nepean Hospital|
|Principal Investigator:||Colin McArthur||ANZIC-RC, Auckland Hospital|
|Principal Investigator:||Simon Erikson||ANZIC-RC,|
|Principal Investigator:||Lynne Murray||ANZIC-RC|
|Principal Investigator:||Suhaini Kadiman||Institut Jantung Negara, Malaysia|
|Principal Investigator:||Jukka Takala||Inselspital, Bern, Switzerland|
|Principal Investigator:||Yaseen Arabi||King Abdulaziz Medical Centre, KSA|
|Principal Investigator:||Matthew P Wise||University Hospital of Wales, UK|