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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT01728558
Registration number
NCT01728558
Ethics application status
Date submitted
4/11/2012
Date registered
20/11/2012
Date last updated
20/08/2019
Titles & IDs
Public title
Early Goal-Directed Sedation Compared With Standard Care in Mechanically Ventilated Critically Ill Patients
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Scientific title
Early Goal-Directed Sedation Compared With Standard Care in Mechanically Ventilated Critically Ill Patients: a Prospective Multicentre Randomised Controlled Trial
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Secondary ID [1]
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ANZIC-RC/YS003
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Universal Trial Number (UTN)
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Trial acronym
SPICE III RCT
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Critical Illness and Mechanical Ventilation
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Condition category
Condition code
Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Other: Early Goal Directed Sedation - Early Goal Directed Sedation process of care involves:
1. Early delivery of proposed intervention, shortly after initiating mechanical ventilation;
2. Effective analgesia provided simultaneously and early (analgesia first).
3. Regular and frequent assessment of patient wakefulness/sedative state;
4. Avoidance of benzodiazepines and minimisation of use of propofol;
5. Reduced overall sedation depth with targeted light sedation; Patients randomised to the EGDS arm will receive a sedative infusion of Dexmedetomidine withor without minimal propofol in order to maintain a RASS of -2 to +1.
Dexmedetomidine infusion will be continued until sedation is no longer clinically indicated up to a maximum of 28 days after enrolment.
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.
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Mortality
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Assessment method [1]
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Timepoint [1]
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Day 90 post randomisation
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Secondary outcome [1]
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Ventilation free days
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Assessment method [1]
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Timepoint [1]
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at 28 days following randomisation
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Secondary outcome [2]
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Proportion of RASS measurements in target range
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Assessment method [2]
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Timepoint [2]
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up to day 28
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Secondary outcome [3]
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Incidence and duration of delirium measured by delirium free days
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Assessment method [3]
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Timepoint [3]
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up to 28 days
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Secondary outcome [4]
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Length of ICU stay
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Assessment method [4]
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Timepoint [4]
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up to 180 days
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Secondary outcome [5]
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Proportion of patients who receive a tracheostomy Proportion of patients who require: re-intubation, physical restraints,or unplanned extubation,
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Assessment method [5]
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Timepoint [5]
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up to day 28
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Secondary outcome [6]
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Cumulative dose of midazolam, propofol, dexmedetomidine, fentanyl, and morphine
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Assessment method [6]
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Timepoint [6]
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up to 28 days
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Secondary outcome [7]
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Duration of treatment with midazolam, propofol, dexmedetomidine, fentanyl, and morphine
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Assessment method [7]
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Timepoint [7]
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up to 28 days
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Secondary outcome [8]
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Mortality at hospital discharge
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Assessment method [8]
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Timepoint [8]
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at hospital discharge up to 180 days
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Secondary outcome [9]
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Length of hospital stay
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Assessment method [9]
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Timepoint [9]
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up to 180 days
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Secondary outcome [10]
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Readmission to ICU
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Assessment method [10]
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Timepoint [10]
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at 90 days
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Secondary outcome [11]
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EQ-5D questionnaire
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Assessment method [11]
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Timepoint [11]
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at 180 days
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Secondary outcome [12]
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Cognitive function
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Assessment method [12]
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Timepoint [12]
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at 180 days
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Secondary outcome [13]
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Mortality at ICU discharge
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Assessment method [13]
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Timepoint [13]
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up to 180 days
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Secondary outcome [14]
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Full time institutional dependency at 180 days
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Assessment method [14]
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Timepoint [14]
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up to 180 days
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Secondary outcome [15]
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Discharge destination
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Assessment method [15]
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Timepoint [15]
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up to 180 days
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Eligibility
Key inclusion criteria
* Patient has been intubated and is receiving mechanical ventilation
* The treating clinician expects that the patient will remain intubated until the day after tomorrow (unlikely to be extubated the following day).
* The patient requires immediate ongoing sedative medication for comfort, safety, and to facilitate the delivery of life support measures.
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
* Age less than 18 years
* Patient is pregnant and/or lactating
* Has been intubated (excluding time spent intubated within an operating theatre or transport) for greater than 12 hours in an intensive care unit.
* Proven or suspected acute primary brain lesion such as traumatic brain injury, intracranial haemorrhage, stroke, or hypoxic brain injury.
* Proven or suspected spinal cord injury or other pathology that may result in permanent or prolonged weakness.
* Admission as a consequence of a suspected or proven drug overdose or burns.
* Administration of ongoing neuromuscular blockade.
* A mean arterial blood (MAP) pressure that is less than 50 mmHg despite adequate resuscitation and vasopressor therapy at time of randomisation
* Heart rate less than 55 beats per minute unless the patient is being treated with a beta-blocker or a high grade atrio-ventricular block in the absence of a functioning pacemaker.
* Known sensitivity to any of the study medications or the constituents of propofol (egg, soya or peanut protein)
* Acute fulminant hepatic failure
* Patient has been receiving full time residential nursing care.
* Death is deemed to be imminent or inevitable during this admission and either the attending physician, patient or substitute decision maker is not committed to active treatment.
* Patient has an underlying disease that makes survival to 90 days unlikely
* Patient has been previously enrolled in the SPICE study.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
1/11/2013
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
1/12/2018
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Sample size
Target
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Accrual to date
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Final
4000
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Recruitment in Australia
Recruitment state(s)
NSW,NT,QLD,SA,TAS,VIC,WA
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Recruitment hospital [1]
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Albury Hospital - Albury
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Blacktown Hospital - Blacktown
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St Vincent's Hospital Sydney - Darlinghurst
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Gosford Hospital - Gosford
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Hornsby Ku-ring-gai Hospital - Hornsby
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Nepean Hospital - Penrith
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Royal North Shore Hospital - St. Leonards
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Prince of Wales Hospital - Sydney
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Westmead Hospital - Westmead
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Royal Darwin Hospital - Tiwi
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Sunshine Coast Hospital (Nambour Hospital) - Buderim
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Royal Brisbane and Women's hospital - Herston
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Redcliffe Hospital - Redcliffe
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Gold Coast Hospital & Health Service - Southport
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Toowoomba Hospital - Toowoomba
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Princess Alexandra Hospital - Woolloongabba
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Lyell McEwan Hospital - Elizabeth Vale
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Royal Hobart Hospital - Hobart
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Launceston General Hospital - Launceston
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Bendigo Hospital - Bendigo
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Dandenong Hospital - Dandenong
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Northern Hospital - Epping
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Geelong Hospital - Geelong
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Austin Hospital - Heidelberg
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Royal Melbourne Hospital - Melbourne
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Monash Medical Centre - Melbourne
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Central Gippsland Health Service - Sale
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Knox Private Hospital - Wantirna
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St John Of God, Subiaco - Perth
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Recruitment postcode(s) [1]
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2640 - Albury
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2148 - Blacktown
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2010 - Darlinghurst
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2250 - Gosford
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Recruitment postcode(s) [5]
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2077 - Hornsby
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Recruitment postcode(s) [6]
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2750 - Penrith
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Recruitment postcode(s) [7]
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2065 - St. Leonards
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Recruitment postcode(s) [8]
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2031 - Sydney
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Recruitment postcode(s) [9]
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2145 - Westmead
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Recruitment postcode(s) [10]
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0811 - Tiwi
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4556 - Buderim
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Recruitment postcode(s) [12]
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4029 - Herston
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Recruitment postcode(s) [13]
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4020 - Redcliffe
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4215 - Southport
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4350 - Toowoomba
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4102 - Woolloongabba
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Recruitment postcode(s) [17]
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5112 - Elizabeth Vale
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7000 - Hobart
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7250 - Launceston
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3550 - Bendigo
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3175 - Dandenong
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3076 - Epping
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3220 - Geelong
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3084 - Heidelberg
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3050 - Melbourne
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3168 - Melbourne
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3850 - Sale
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3152 - Wantirna
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Recruitment postcode(s) [29]
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6008 - Perth
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Recruitment outside Australia
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Ireland
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Dublin 4
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Ireland
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Dublin 8
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Italy
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Milan
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Malaysia
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Kelantan
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Malaysia
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Pulau Pinang
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Malaysia
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Sabah
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Malaysia
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Sarawak
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Malaysia
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Kuala Lumpur
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Malaysia
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Melaka
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New Zealand
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Auckland
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New Zealand
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Christchurch
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New Zealand
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New Zealand
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Wellington
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New Zealand
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Dunedin
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New Zealand
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Rotorua
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Saudi Arabia
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Riyadh
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Switzerland
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Bern
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United Kingdom
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London
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United Kingdom
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Newcastle Upon Tyne
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Norfolk
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Plymouth
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Stockton-on-Tees
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Birmingham
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Bournemouth
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Bristol
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Cardiff
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Coventry
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United Kingdom
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Dorchester
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Edinburgh
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Liverpool
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Londonderry
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United Kingdom
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Orpington
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United Kingdom
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Reading
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Funding & Sponsors
Primary sponsor type
Other
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Name
Australian and New Zealand Intensive Care Research Centre
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Address
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Other collaborator category [1]
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Other
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Name [1]
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National Health and Medical Research Council, Australia
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Address [1]
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Ethics approval
Ethics application status
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Summary
Brief summary
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: 1. Early randomization after intubation or arrival in the ICU (intubated). 2. Early Adequate analgesia after randomization. 3. Goal directed sedation titrated to achieve light sedation. 4. 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.
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Trial website
https://clinicaltrials.gov/study/NCT01728558
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Trial related presentations / publications
Shehabi Y, Bellomo R, Reade MC, Bailey M, Bass F, Howe B, McArthur C, Seppelt IM, Webb S, Weisbrodt L; Sedation Practice in Intensive Care Evaluation (SPICE) Study Investigators; ANZICS Clinical Trials Group. Early intensive care sedation predicts long-term mortality in ventilated critically ill patients. Am J Respir Crit Care Med. 2012 Oct 15;186(8):724-31. doi: 10.1164/rccm.201203-0522OC. Epub 2012 Aug 2. Shehabi Y, Serpa Neto A, Bellomo R, Howe BD, Arabi YM, Bailey M, Bass FE, Bin Kadiman S, McArthur CJ, Reade MC, Seppelt IM, Takala J, Wise MP, Webb SA; SPICE III Study Investigators. Dexmedetomidine and Propofol Sedation in Critically Ill Patients and Dose-associated 90-Day Mortality: A Secondary Cohort Analysis of a Randomized Controlled Trial (SPICE III). Am J Respir Crit Care Med. 2023 Apr 1;207(7):876-886. doi: 10.1164/rccm.202206-1208OC. Cioccari L, Luethi N, Bailey M, Shehabi Y, Howe B, Messmer AS, Proimos HK, Peck L, Young H, Eastwood GM, Merz TM, Takala J, Jakob SM, Bellomo R; ANZICS Clinical Trials Group and the SPICE III Investigators. The effect of dexmedetomidine on vasopressor requirements in patients with septic shock: a subgroup analysis of the Sedation Practice in Intensive Care Evaluation [SPICE III] Trial. Crit Care. 2020 Jul 16;24(1):441. doi: 10.1186/s13054-020-03115-x. Shehabi Y, Howe BD, Bellomo R, Arabi YM, Bailey M, Bass FE, Bin Kadiman S, McArthur CJ, Murray L, Reade MC, Seppelt IM, Takala J, Wise MP, Webb SA; ANZICS Clinical Trials Group and the SPICE III Investigators. Early Sedation with Dexmedetomidine in Critically Ill Patients. N Engl J Med. 2019 Jun 27;380(26):2506-2517. doi: 10.1056/NEJMoa1904710. Epub 2019 May 19. Moore JPR, Anstey C, Murray L, Fraser JF, Singer M. Allostasis and sedation practices in intensive care evaluation: an observational pilot study. Intensive Care Med Exp. 2018 Jun 20;6(1):13. doi: 10.1186/s40635-018-0179-0.
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Public notes
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Contacts
Principal investigator
Name
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Yahya Shehabi, MD, FCICM, FANZCA, EMBA
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Address
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University New South Wales, Prince of Wales Hospital, ANZIC-RC
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Contact person for scientific queries
No information has been provided regarding IPD availability
What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results not provided in
https://clinicaltrials.gov/study/NCT01728558
Download to PDF