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Trial registered on ANZCTR


Registration number
ACTRN12619000939190
Ethics application status
Approved
Date submitted
17/06/2019
Date registered
5/07/2019
Date last updated
5/07/2019
Date data sharing statement initially provided
5/07/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Assessment of narcotic administration to lead to analgesic effects and sedation in intensive care
Scientific title
A multi-centre, cluster, crossover, pilot study comparing the efficacy of morphine with fentanyl for analgo-sedation in intestine care patients requiring invasive mechanical ventilation
Secondary ID [1] 298517 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pain 313322 0
Condition category
Condition code
Anaesthesiology 311761 311761 0 0
Pain management

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study will use a design know as a ‘cluster crossover design’. There will be two study treatment periods. Each period is 6 months in duration. There is no washout period between treatments. Following randomised blinded allocation using sealed opaque envelopes, during the first treatment period, one of the ICUs will be instructed to use only morphine or fentanyl for pain relief and sedation in patients who are receiving mechanical ventilation, while the other ICU will be instructed to use morphine or fentanyl. During the second treatment period, each ICU will swap to using the opposite treatment. This means that, in situations where morphine and fentanyl are regarded as being equivalent by the treating clinician, the treatment administered will be determined based on the treatment assigned to the ICU. However, if there is a specific indication NOT to use one or other of the drugs (e.g. an allergy to the drug), then the treatment will be allocated irrespective of the treatment assigned to the ICU, and will be up to the treating clinician. An audit of pharmacy medicine supply logs and a site log of patients with identified contra-indications will be performed.
Intervention code [1] 314765 0
Treatment: Drugs
Comparator / control treatment
Morphine
Control group
Active

Outcomes
Primary outcome [1] 320441 0
Invasive mechanical ventilation-free days
Timepoint [1] 320441 0
From the date of ICU admission and censored at day 28 as determined via medical record audit.
Secondary outcome [1] 371604 0
Intensive care unit free days assessed via medical record audit of existing hospital pharmacy database and patient hospital database..
Timepoint [1] 371604 0
From the date of intensive care unit admission and censored at day 28.
Secondary outcome [2] 371605 0
Hospital free days via medical record audit of existing patient hospital electronic databases.
Timepoint [2] 371605 0
From the date of intensive care unit admission until hospital discharge and censored at day 28
Secondary outcome [3] 371606 0
Intensive care unit mortality via medical record audit of existing patient hospital electronic databases.
Timepoint [3] 371606 0
Mortality occurring within the intensive care unit from the date of the intensive care unit admission and censored at day 28.
Secondary outcome [4] 371607 0
Hospital mortality via medical record audit of existing patient hospital electronic databases.
Timepoint [4] 371607 0
Mortality occurring within the hospital from the date of the intensive care unit admission and censored at day 28.
Secondary outcome [5] 371608 0
New requirement for a tracheostomy insertion via medical record audit of existing patient hospital electronic databases.
Timepoint [5] 371608 0
The requirement for the insertion of a new tracheostomy from the date of intensive care unit admission until intensive care unit discharge and censored at day 28.
Secondary outcome [6] 371610 0
Total dose of unit-based use of propofol medicine via an audit of the existing hospital pharmacy database.
Timepoint [6] 371610 0
Unit total dose of propofol supplied by the hospital's pharmacy during the 6-month intervention period or both 'morphine' arm and 'fentanyl' arm periods.
Secondary outcome [7] 371611 0
Total unit-based dose of midazolam medicine via an audit of the existing hospital pharmacy database.
Timepoint [7] 371611 0
Unit total dose of midazolam supplied by the hospital's pharmacy during the 6-month intervention period or both 'morphine' arm and 'fentanyl' arm periods.
Secondary outcome [8] 371612 0
Total unit-dose of dexmedetomidine medicine via an audit of the existing hospital pharmacy database.
Timepoint [8] 371612 0
Unit total dose of dexmedetomidine supplied by the hospital's pharmacy during the 6-month intervention period or both 'morphine' arm and 'fentanyl' arm periods.
Secondary outcome [9] 371613 0
Cost of propofol used during study period.
Timepoint [9] 371613 0
Unit cost of propofol supplied by the hospital's pharmacy during the 6-month intervention period or both 'morphine' arm and 'fentanyl' arm periods.
Secondary outcome [10] 371614 0
Cost of midazolam used during the study period.
Timepoint [10] 371614 0
Unit cost of midazolam supplied by the hospital's pharmacy during the 6-month intervention period or both 'morphine' arm and 'fentanyl' arm periods.
Secondary outcome [11] 371615 0
Cost of midazolam used during study period.
Timepoint [11] 371615 0
Unit cost of dexmedetomidine supplied by the hospital's pharmacy during the 6-month intervention period or both 'morphine' arm and 'fentanyl' arm periods.
Secondary outcome [12] 371616 0
Adverse events identified by the patient's treating intensive care unit doctors that are requiring the cessation of morphine or fentanyl. Such events may include very low respiratory rates, drug allergy or over-sedation.
Timepoint [12] 371616 0
Reported cessation of the prescribed agent - either morphine or fentanyl - during the relevant study period as reported by the trial site treating doctors to the investigating team members.

Eligibility
Key inclusion criteria
Aged equal to or greater than 18 years of age
Receiving mechanical ventilation
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Admission to the intensive care unit following cardiac surgery.
Allergic to morphine
Allergic to fentanyl

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Cluster crossover trial
Phase
Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis
These two agents have never been directly compared in any trials in mechanically ventilated adult ICU patients. This is therefore a pilot study order to determine feasibility of comparing these two agents, as well as to establish the primary outcome of invasive mechanical ventilation-free days at day 28 using the two agents for analgo-sedation. Furthermore, it will be used to establish baseline data within the secondary outcome measures including cost, use of other sedative agents (as a surrogate for effectiveness – the less other sedatives used, the more effective the agent), ICU and hospital free days at day 28. As such, the trial drugs will be used for defined periods of 6 months at each hospital, rather than aiming for a particular number of patients recruited. Provisional estimates of mechanically ventilated patients at each hospital would suggest that approximately 1,000 patients will be recruited. Thus, assuming from previous ICU studies a mean invasive ventilation free days of 16 days with a standard deviation of 15 days, the proposed study would have an 88% power to detect a difference of 3 days (RRR of 18.7%) between the two drugs at an alpha of 0.05.

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)
VIC
Recruitment hospital [1] 14009 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [2] 14010 0
The Northern Hospital - Epping
Recruitment postcode(s) [1] 26789 0
3084 - Heidelberg
Recruitment postcode(s) [2] 26790 0
3076 - Epping

Funding & Sponsors
Funding source category [1] 303063 0
Hospital
Name [1] 303063 0
Austin Hospital
Address [1] 303063 0
145 Studley Road
Heidelberg
Victoria 3084
Country [1] 303063 0
Australia
Primary sponsor type
Hospital
Name
Austin Health
Address
145 Studley Road
Heidelberg
Victoria 3084
Country
Australia
Secondary sponsor category [1] 303045 0
Individual
Name [1] 303045 0
Professor Rinaldo Bellomo
Address [1] 303045 0
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg
Victoria 3084
Country [1] 303045 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303613 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 303613 0
C/o Austin Health
145 Studley Road
Heidelberg
Victoria 3084
Ethics committee country [1] 303613 0
Australia
Date submitted for ethics approval [1] 303613 0
Approval date [1] 303613 0
09/05/2019
Ethics approval number [1] 303613 0
HREC/52656/Austin-2019

Summary
Brief summary
Patients who are receiving invasive mechanical ventilation treatment are often prescribed a combination of medications to help keep them calm (sedated), and also to remove pain and discomfort. Two commonly used drugs to relieve discomfort are morphine and fentanyl. These are part of the narcotic group of drugs. Currently, either of these agents is prescribed to many thousands of patients in intensive care units in Australia and New Zealand every year. This study will aim to establish which of these two medications that are commonly used for pain relief and sedation in patients receiving treatment with a breathing machine is better with regards to being able to remove the breathing machine earlier, in addition to decreasing the amount of other medications that may be required for sedation and relief of pain or discomfort.

Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 94262 0
Dr Andrew Casamento
Address 94262 0
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg
Victoria 3084
Country 94262 0
Australia
Phone 94262 0
+61 3 9496 6849
Fax 94262 0
+61394963932
Email 94262 0
andrew.casamento@austin.org.au
Contact person for public queries
Name 94263 0
Dr Glenn Eastwood
Address 94263 0
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg
Victoria 3084
Country 94263 0
Australia
Phone 94263 0
+61 3 9496 4835
Fax 94263 0
+61 3 9496 3932
Email 94263 0
glenn.eastwood@austin.org.au
Contact person for scientific queries
Name 94264 0
Dr Andrew Casamento
Address 94264 0
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg
Victoria 3084
Country 94264 0
Australia
Phone 94264 0
+61 3 9496 6849
Fax 94264 0
+61394963932
Email 94264 0
andrew.casamento@austin.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Undecided policy at present time
What supporting documents are/will be available?
Ethical approval
How or where can supporting documents be obtained?
Type [1] 2369 0
Ethical approval
Citation [1] 2369 0
Link [1] 2369 0
Email [1] 2369 0
Other [1] 2369 0
Summary results
No Results