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Trial registered on ANZCTR


Registration number
ACTRN12614000225617
Ethics application status
Not yet submitted
Date submitted
13/02/2014
Date registered
3/03/2014
Date last updated
3/03/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
Sedation Practice in Intensive Care: A randomised controlled pilot study
Scientific title
A randomised controlled pilot trial of early goal-directed sedation in paediatric intensive care.
Secondary ID [1] 284097 0
Nil
Universal Trial Number (UTN)
Trial acronym
Baby Spice Pilot Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Sedation in patients mechanically ventilated in paediatric intensive care 291170 0
Condition category
Condition code
Anaesthesiology 291504 291504 0 0
Anaesthetics
Physical Medicine / Rehabilitation 291505 291505 0 0
Other physical medicine / rehabilitation
Public Health 291506 291506 0 0
Epidemiology

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Early goal directed sedation consisting of a dexmedetomidine based sedation protocol:
The primary sedative agent in the intervention arm is dexmedetomidine delivered by continuous infusion without a loading dose, supplemented by alternative sedative agents as outlined below, to achieve the level of sedation specified by the treating clinician.
Effective pain relief is provided by an infusion or boluses of an opioid (eg morphine or fentanyl) or other agent (eg ketamine) at the discretion of the treating clinician. This is particularly important during painful or noxious procedures (eg. endotracheal suction)
Dexmedetomidine arm [known as GpDex]: refer to study algorithm
Commence dexmedetomidine infusion at 1.0 mcg/kg/hr without a loading dose. This will take about 45 minutes to produce full sedative effect.
Dexmedetomidine infusion will be titrated to sedative effect up to a maximum dose of 1.4 mcg/kg/hr (depending on age: 0-1 yrs 1.0 micrograms/kg/hour, 1-5 years 1.4 mcg/kg/hr, 5-10 years 1.3 mcg/kg/hr, >10 years 1.0 mcg/kg/hr) with dose of infusion specified by the treating clinician to achieve the desired level of sedation specified by the treating clinician.
a) Dexmedetomidine infusion will be continued until sedation is no longer required to a maximum of 14 days after enrolment.
2) Boluses or infusion or both of opioids, as chosen by the treating clinician, will be administered, if required, at a dose specified by the treating clinician to provide analgesia
3) Alternative sedative agents may be considered if a combination of dexmedetomidine and opioid infusions do not provide sufficient sedation. Examples include ketamine, chloral hydrate, sedating anti-histamines, phenobarbitone as per physician preference
4) Supplemental propofol can be used (up to a maximum of 24 hours and a maximum dose of 4 mg/kg/hr, in accordance with individual intensive care unit policy), always at the lowest effective dose to:
a) Provide sedation during commencement and initial titration of dexmedetomidine infusion
b) To optimise sedation to achieve the level of sedation specified by the treating clinician at any time when dexmedetomidine alone and at maximum dose is insufficient to provide patient comfort and safety
c) Provide rescue sedation for immediate control of sudden agitation at any time
d) Provide additional sedation during procedures
5) Benzodiazepines (such as midazolam, diazepam and clonazepam) may be administered if sufficient level of sedation is not attained with the above measures.
6) Clonidine should not be administered concurrently with dexmedetomidine (although may used to prevent or treat suspected dexmedetomidine withdrawal).
Intervention code [1] 288790 0
Treatment: Drugs
Comparator / control treatment
Standard sedation protocol:
The primary sedative agent in GpStd is at the discretion of the treating clinician. This can be any agent or combination of agents EXCEPT that dexmedetomidine can only be used as a last resort. Selected agents can be given by infusion or boluses to achieve the level of sedation specified by the treating clinician.
1. Boluses or infusion or both of selected opioid or other agent/s chosen by the treating clinician, will be administered at a dose specified by the treating clinician to provide analgesia.
2. Midazolam infusion (50-250 mcg/kg/hr) or other benzodiazepines. (1-4 mcg/kg/minute)
3. Second line sedatives including chloral hydrate, clonidine (as per individual unit protocols), ketamine, barbiturates
4. Supplemental propofol can be used (up to a maximum of 24 hours and a maximum dose of 4 mg/kg/hr, in accordance with individual intensive care unit policy), always at the lowest effective dose to:
a. Provide additional sedation during procedures
b. Provide rescue sedation for immediate control of sudden agitation at any time.
Control group
Active

Outcomes
Primary outcome [1] 291479 0
The primary outcome measure for the pilot study is to demonstrate separation between the intervention group (GpDex) and a ‘wild-type’ (usual practice) control group (GpStd) with respect to the proportion of patients achieving light sedation (SBS -1 to +1) in the first 48 hours of sedation in intensive care
The primary outcome will be assessed by comparing the proportion of patients in light sedation in the intervention group comparted to the proportion of patients in light sedation in the comparator group.
Timepoint [1] 291479 0
48 hours
Secondary outcome [1] 306869 0
The cumulative and daily dose of dexmedetomidine, midazolam, propofol, clonidine, ketamine, fentanyl, morphine and other sedatives
This outcome will be assessed by measuring the total doses of each drug (units per kilogram)received over the study period.
Timepoint [1] 306869 0
The cumulative dose of drugs used will be assessed daily up to 14 days or ICU discharge (if less than 14 days)
Secondary outcome [2] 306870 0
The proportion of patients in SBS categories -2 to -3 (deep sedation), -1 to +1 (light sedation) and +2, assessed daily in ventilated patients still receiving sedative infusions
Timepoint [2] 306870 0
This will be assessed daily up to 14 days or ICU discharge
Secondary outcome [3] 306871 0
Duration of mechanical ventilation
Timepoint [3] 306871 0
Assessed at 90 days from initiation of ventilation
Secondary outcome [4] 306872 0
Adverse drug effects will be assessed daily by research coordinators.
Possible adverse effects include:
1. Hypotension
2. Bradycardia
3. Deep sedation
4. Drug withdrawal syndromes.
Timepoint [4] 306872 0
Patients will assessed daily for the occurrence of adverse drug effects up until 90 days from initiation of ventilation
Secondary outcome [5] 306873 0
Unplanned extubations/loss of vascular lines.
These adverse effects will be assessed daily until discharge from ICU by continual nursing observation
Timepoint [5] 306873 0
Assessed at ICU discharge
Secondary outcome [6] 306874 0
Vital status at hospital discharge and after 90 days of follow up
Timepoint [6] 306874 0
Assessed at hospital discharge and on 90 day follow-up by phone call
Secondary outcome [7] 306875 0
Proportion of screened and eligible patients who were recruited.


Timepoint [7] 306875 0
At the completion of 90 days after recruitment
Secondary outcome [8] 306960 0
Protocol fidelity: The number of protocol violations will be assessed and a description of protocol violations will be provided
Timepoint [8] 306960 0
This will be assessed at ICU discharge
Secondary outcome [9] 306961 0
Duration of ICU stay
Timepoint [9] 306961 0
Assessed at ICU discharge
Secondary outcome [10] 306962 0
Duration of hospital stay
Timepoint [10] 306962 0
Assessed at hospital discharge
Secondary outcome [11] 306963 0
Proportion of patients recruited who are ventilated for more than 24 hours. This is the number of patients ventilated for more than 24 hours divided by the number of patients recruited. This will be assessed at the completion of detailed data collection (14 days after recruitment)
Timepoint [11] 306963 0
Assessed at ICU discharge
Secondary outcome [12] 306964 0
Duration from time of intubation to time of randomisation and time from randomisation to time of commencement of sedative medications
Timepoint [12] 306964 0
Assessed at ICU discharge
Secondary outcome [13] 306965 0
Retention of subjects to 90 day follow-up
Timepoint [13] 306965 0
Assessed at 90 day follow-up

Eligibility
Key inclusion criteria
Children requiring sedation to facilitate mechanical ventilation in intensive care.
Subject has been mechanically ventilated for less than 12 hours
Patient is expected to remain mechanically ventilated for more than 24 hours
Minimum age
0 Days
Maximum age
15 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Age 16 years or older
Proven or suspected acute primary brain lesion that may result in global impairment of conscious level or cognition, such as traumatic brain injury, intracranial haemorrhage, intracranial infection or hypoxic brain injury.
Proven or suspected neurological injury or pathology that may result in permanent or prolonged weakness of upper and lower limbs.
Burn injuries
Receiving or expected to need continuous neuromuscular blockade
Allergy to dexmedetomidine
Cardiovascular instability as manifested by any of the following:
a. Mean arterial blood (MAP) pressure less than 2 standard deviations below the normal mean for age despite resuscitation and vasopressor therapy
b. Heart rate (HR) less than 2 standard deviations below normal for age
c. Atrio-ventricular block (2nd or 3rd degree) in the absence of a functioning pacemaker
End stage liver failure or acute fulminant hepatic failure
A history of a chronic brain process that has resulted in severe global impairment of conscious level or cognition, and may include CP, metabolic conditions, and progressive neurological disorders
Patient is on ECLS
Death is deemed imminent and inevitable
There is an underlying disease that makes survival to 90 days unlikely

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Subjects will be indentified in intensive care and guardians approached for consent.
All patients in participating units will be screened within 12-hours of admission to intensive care.
Subjects will be randomised by sealed envelope allocation.
Randomisation will be stratified to each study centre
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Patients who satisfy inclusion criteria and have no exclusion criteria will be randomly assigned in a 1:1 ratio to either a dexmedetomidine arm (GpDex) or to a standard treatment arm (GpStd). Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation) will be used. Subjects will be stratified by centre
Subjects will be stratified per centre
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis
This is a feasibility trial of 2 randomised sedative interventions used in critically ill patients, with the primary outcome being the difference in the proportion of time patients successfully achieve light sedation (SBS -1 to +1) in the first 48 hours of sedation in intensive care in each arm. Although this can be achieved in a small number of subjects, a sample size of 60 subjects will be sufficient to show a difference of at least 25% in the proportion of SBS scores in the light sedation range (SBS -1 to +1) in the intervention arm as compared to the standard arm, in the first 48 hours, and allow meaningful assessment of important secondary outcomes. Means with standard deviation for normally distributed variables and medians with interquartile ranges for non-normally distributed continuous variables, and proportions with 95% confidence limits, will be reported. If feasible, a logistic regression analysis will be used to identify factors such as site or patient characteristics that are associated with a particular pattern of sedation or clinical practice, such as deviation from the targeted level of sedation or inappropriate ‘deep’ sedation.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA,VIC
Recruitment hospital [1] 2088 0
Princess Margaret Hospital - Subiaco
Recruitment hospital [2] 2089 0
Royal Children's Hospital - Herston
Recruitment hospital [3] 2090 0
The Royal Childrens Hospital - Parkville
Recruitment hospital [4] 2091 0
The Children's Hospital at Westmead - Westmead
Recruitment postcode(s) [1] 7777 0
2145 - Westmead
Recruitment postcode(s) [2] 7776 0
3052 - Parkville
Recruitment postcode(s) [3] 7775 0
4006 - Herston
Recruitment postcode(s) [4] 7774 0
6008 - Subiaco
Recruitment outside Australia
Country [1] 5824 0
New Zealand
State/province [1] 5824 0

Funding & Sponsors
Funding source category [1] 288724 0
Commercial sector/Industry
Name [1] 288724 0
Hospira
Unrestricted research grant
Address [1] 288724 0
275 N Field Dr, Lake Forest, Illinois, 60045, United States
Country [1] 288724 0
United States of America
Funding source category [2] 288725 0
Hospital
Name [2] 288725 0
Princess Margaret Hospital Foundation
Seeding grant
Address [2] 288725 0
Roberts Rd
Subiaco 6008
Western Australia
Country [2] 288725 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australia and NewZealand Intensive Care-Research Centre (ANZIC-RC)
Address
ANZIC Research Centre
Monash University
Level 6
The Alfred Centre
99 Commercial Road
MELBOURNE VIC 3004
Country
Australia
Secondary sponsor category [1] 287425 0
Hospital
Name [1] 287425 0
Princess Margaret Hospital
Address [1] 287425 0
Roberts Rd
Subiaco 6008
WA
Country [1] 287425 0
Australia

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 290562 0
Princess Margaret Hospital Human Research Ethics Committee
Ethics committee address [1] 290562 0
Roberts Rd
Subiaco 6008
Western Australia
Ethics committee country [1] 290562 0
Australia
Date submitted for ethics approval [1] 290562 0
13/02/2014
Approval date [1] 290562 0
Ethics approval number [1] 290562 0
Ethics committee name [2] 290563 0
National Human Research Ethics Committee
Ethics committee address [2] 290563 0
Ethics committee country [2] 290563 0
Australia
Date submitted for ethics approval [2] 290563 0
Approval date [2] 290563 0
Ethics approval number [2] 290563 0

Summary
Brief summary
This pilot study aims to evaluate the feasibility of conducting a large scale multicentre RCT in paediatric intensive care, comparing current sedation practice with a dexmedetomidine based sedation regimen that minimizes benzodiazepines.
Trial website
www.spicestudy.org/
Trial related presentations / publications
1. Australia and New Zealand Intensive Care Society Annual Scientific Meeting, Hobart 2013
Baby SPICE Observational Study
Presented by Dr. Debbie Long

2. baby SPICE Pilot Protocol
ANZICS Clinical Trials Group ASM, Noosa, QLD 2013
Presented by Dr. Simon Erickson
Public notes

Contacts
Principal investigator
Name 46266 0
Dr Simon Erickson
Address 46266 0
Princess Margaret Hospital
Roberts Rd
Subiaco 6008
Western Australia
Country 46266 0
Australia
Phone 46266 0
+61893408447
Fax 46266 0
+61893882772
Email 46266 0
simon.erickson@health.wa.gov.au
Contact person for public queries
Name 46267 0
Dr Simon Erickson
Address 46267 0
Princess Margaret Hospital
Roberts Rd
Subiaco 6008
Western Australia
Country 46267 0
Australia
Phone 46267 0
+61893408447
Fax 46267 0
+61893882772
Email 46267 0
simon.erickson@health.wa.gov.au
Contact person for scientific queries
Name 46268 0
Dr Simon Erickson
Address 46268 0
Princess Margaret Hospital
Roberts Rd
Subiaco 6008
Western Australia
Country 46268 0
Australia
Phone 46268 0
+61893408447
Fax 46268 0
+61893882772
Email 46268 0
simon.erickson@health.wa.gov.au

No information has been provided regarding IPD availability
Summary results
No Results