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Trial registered on ANZCTR


Registration number
ACTRN12615001358538
Ethics application status
Approved
Date submitted
8/12/2015
Date registered
15/12/2015
Date last updated
8/01/2019
Date data sharing statement initially provided
8/01/2019
Date results information initially provided
8/01/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
The Safety and Efficacy of Perioperative Dexmedetomidine in Cardiac Surgery Patients - A Pilot Trial
Scientific title
The Safety and Efficacy of Perioperative Dexmedetomidine in Cardiac Surgery Patients - A
Pilot Trial
Secondary ID [1] 288096 0
none
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Combined coronary artery bypass graft surgery and valve surgery 296956 0
Valve surgery 296972 0
Aortic arch surgery 296973 0
Condition category
Condition code
Cardiovascular 297218 297218 0 0
Other cardiovascular diseases
Anaesthesiology 297229 297229 0 0
Anaesthetics

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intervention: Dexmedetomidine infusion at 0.7 mcg/kg/hr will commence at the induction of anaesthesia and be continued throughout the surgery. Dose will be reduced by 0.4 mcg/kg/hr at skin closure and continue until clinically not required.
All anaesthetic agents including inhalational agents, Propofol, Midazolam, Diazepam and narcotics including Fentanyl and Morphine can be used according to the routine practice of the anaesthetist and to maintain desired anaesthesia depth
The drug will be discontinued if the treating physician thinks that the patient is at risk. The drug will be discontinued at extubation in ICU or just before the patient leaves the ICU. This will be decided by the treating consultant.
Intervention code [1] 293402 0
Treatment: Drugs
Intervention code [2] 293416 0
Prevention
Comparator / control treatment
Standard anesthesia.

Intraoperative management of anaesthesia will be at the discretion of the anaesthetist in charge and according to routine practice, routine monitoring as per standard for cardiac surgery.
It is recommended that anaesthetic depth is monitored in ALL patients using a processed EEG signal such as Bispectral Index (BIS) and kept between 40 – 60.
All anaesthetic agents including inhalational agents, Propofol, Midazolam, Diazepam and narcotics including Fentanyl and Morphine can be used according to the routine practice of the anaesthetist and to maintain desired anaesthesia depth.
Control group
Active

Outcomes
Primary outcome [1] 296806 0
This is a composite primary outcome of number of days home, alive and disability free at 28 days following surgery. A research coordinator will call the participants to check that they are still alive and how long they have been at home. If a patient is alive, a number of pre-written questions to assess the quality of life of the participant will be asked by the research coordinator.
Timepoint [1] 296806 0
28 days post hospital discharge
Secondary outcome [1] 319409 0
hospital mortality. This will be looked up on the IPM database that the hospital uses for patient data collection.
Timepoint [1] 319409 0
hospital stay
Secondary outcome [2] 319410 0
Acute kidney injury, This will be assessed by the treating consultant.
Timepoint [2] 319410 0
During ICU stay
Secondary outcome [3] 319411 0
Delirium. This will be assessed by preforming CAM-ICU
Timepoint [3] 319411 0
Assessed daily during ICU stay.
Secondary outcome [4] 319412 0
major adverse cardiac events (MACE). The treating consultant will determine if MACE has occurred during the daily patient rounds. This will be entered in the patient notes. MACE includes; myocardial infarction (MI), stroke, and heart failure
Timepoint [4] 319412 0
During ICU stay
Secondary outcome [5] 319443 0
ICU mortality. This will be looked up on the IPM database that the hospital uses for patient data collection
Timepoint [5] 319443 0
During ICU stay
Secondary outcome [6] 319444 0
Major adverse kidney events (MAKE). The treating consultant will determine if MAKE has occurred during the daily patient rounds. This will be entered in the patient notes. MAKE includes; new dialysis, and worsened renal function
Timepoint [6] 319444 0
During ICU stay
Secondary outcome [7] 319445 0
Agitation. This will be measured by using the Agitated Behavior Scale
Timepoint [7] 319445 0
This will be assessed daily throughout ICU admission

Eligibility
Key inclusion criteria
1) Older than 18 years of age
2) Patients undergoing combined cardiac surgery (CABG + valve) or (Double valve) or major aortic arch surgery
3) GFR<60
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) Patients <18 years
2) CKD stage IV (eGFR<20 ml/min/1.72m2) or Dialysis dependent patients
3) Planned off pump cardiac surgery, salvage surgery, extracorporeal support, high grade AV block in the absence of pacemaker
4) Allergy to dexmedetomidine
5) Severe hepatic impairment defined as Child C liver disease

Study design
Purpose of the study
Prevention
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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
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,VIC
Recruitment hospital [1] 4864 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [2] 4865 0
Prince of Wales Hospital - Randwick
Recruitment hospital [3] 4866 0
The Alfred - Prahran
Recruitment hospital [4] 4867 0
Austin Health - Austin Hospital - Heidelberg
Recruitment postcode(s) [1] 12372 0
2031 - Randwick
Recruitment postcode(s) [2] 12371 0
3084 - Heidelberg
Recruitment postcode(s) [3] 12369 0
3168 - Clayton
Recruitment postcode(s) [4] 12370 0
3181 - Prahran

Funding & Sponsors
Funding source category [1] 292519 0
Hospital
Name [1] 292519 0
Monash Medical Centre
Address [1] 292519 0
246 Clayton Rd, Clayton VIC 3168
Country [1] 292519 0
Australia
Primary sponsor type
Hospital
Name
Monash Medical Centre
Address
246 Clayton Rd, Clayton VIC 3168
Country
Australia
Secondary sponsor category [1] 291226 0
None
Name [1] 291226 0
Address [1] 291226 0
Country [1] 291226 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293996 0
The Monash Health Human Research Ethics Committee
Ethics committee address [1] 293996 0
246 Clayton Rd, Clayton VIC 3168
Ethics committee country [1] 293996 0
Australia
Date submitted for ethics approval [1] 293996 0
25/11/2015
Approval date [1] 293996 0
24/02/2016
Ethics approval number [1] 293996 0
HREC/15/MonH/194

Summary
Brief summary
Cardiac surgery is one of the most common complex operations conducted on millions of patients worldwide every year. Advances in bypass technology and surgical techniques improved mortality and outcomes after cardiac surgery. Patients presenting to cardiac surgery are older, suffer multiple comorbidity and likely to undergo more complex operations. Therefore, significant morbidity continues to be associated with cardiac surgery including acute kidney injury and failure, neurological injury such as stroke, delirium or cognitive dysfunction, cardiac failure and arrhythmias such as atrial fibrillation and respiratory failure. These complications, in combination or individually, leads to increased hospital stay and increased disability and functional dependence.
Dexmedetomidine is a strong sympatholytic agent that has been used as a sedative and adjunct for procedural sedation. Animal models of global hypoxic brain injury, myocardial ischaemia reperfusion and contrast induced kidney injury showed potential protective effects, possibly due to reduced apoptosis and inflammatory response. A Cochrane systematic review concluded that the perioperative use of Alpha2 agonist reduced mortality and myocardial ischaemia with most pronounced effect seen in vascular and cardiac surgery. In the context of cardiac surgery, randomised trials of dexmedetomidine has been shown to reduce delirium, acute kidney injury and postoperative ventilation time. Retrospective propensity score analysis suggested that dexmedetomidine reduced
hospital and 1 year mortality in patients undergoing cardiac surgery. In concert, these studies suggest that perioperative use of dexmedetomidine may reduce cardiac surgery associated complications, including mortality and likely to days home and disability free following high risk cardiac surgery.
Aims:
1. Assess the safety and efficacy of perioperative dexmedetomidine in high risk cardiac surgery.
2. Inform the design and conduct of a phase III multicentre study on the clinical effectiveness of dexmedetomidine in cardiac surgery
Design: Multicentre Single blind placebo controlled RCT
Population and sample size: 80 patients in 4 sites
Inclusion criteria: consenting adult patients undergoing on bypass cardiac surgery with
1. Combined surgery (CABG + valve) or (valve) or aortic arch surgery OR
2. Chronic Kidney disease class III and IV with estimated GFR 1559
mls/min/1.72m2.
Intervention: Dexmedetomidine infusion at 0.7 mcg/kg/hr will commence at the induction of anaesthesia and be continued throughout the surgery. Dose will be reduced by 0.4 mcg/kg/hr at skin closure and continue until clinically not required.
Concomitant intervention: Standard anaesthesia.
Primary outcomes: A composite outcome of number of days home, alive and disability free at 28 days following surgery will be the primary study outcome.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 62034 0
Prof Yahya Shehabi
Address 62034 0
Prof. Yahya Shehabi
Monash Medical Centre
Level 2, E Block
246 Clayton Road
3168 Clayton Victoria
Australia
Country 62034 0
Australia
Phone 62034 0
+61 3 95942730
Fax 62034 0
Email 62034 0
yahya.shehabi@moanshhealth.org
Contact person for public queries
Name 62035 0
Dr Maja Green
Address 62035 0
Dr Maja Green
Monash Medical Centre
246 Clayton Road
3168 Clayton Victoria
Australia
Country 62035 0
Australia
Phone 62035 0
+61 3 95943068
Fax 62035 0
Email 62035 0
maja.green@monashhealth.org
Contact person for scientific queries
Name 62036 0
Dr Maja Green
Address 62036 0
Dr Maja Green
Monash Medical Centre
246 Clayton Road
3168 Clayton Victoria
Australia
Country 62036 0
Australia
Phone 62036 0
+61 3 95943068
Fax 62036 0
Email 62036 0
maja.green@monashhealth.org

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Data presented in pooled format
What supporting documents are/will be available?
Study protocol
Informed consent form
Ethical approval
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary