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Trial registered on ANZCTR


Registration number
ACTRN12615001071516
Ethics application status
Approved
Date submitted
23/09/2015
Date registered
13/10/2015
Date last updated
9/01/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Evaluation of dexmedetomidine in intensive care unit patients with severe sepsis: a retrospective cohort study
Scientific title
A retrospective evaluation of the impact of dexmedetomidine compared to standard care sedation on the blood pressure of patients who have severe infections and who require mechanical ventilation.
Secondary ID [1] 287531 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Sepsis 296298 0
Mechanical ventilation 296362 0
Condition category
Condition code
Cardiovascular 296576 296576 0 0
Other cardiovascular diseases
Anaesthesiology 296637 296637 0 0
Anaesthetics
Infection 296638 296638 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Mechanically ventilated patients admitted to the intensive care unit with confirmed or suspected sepsis who were treated with dexmedetomidine as a part of their care while admitted to the Austin Hospital between November 2013 and June 2015. All data will be retrieved from the participants medical record and with the duration of the observation period to include the duration of ICU stay and hospital admission.
Intervention code [1] 292929 0
Not applicable
Comparator / control treatment
Standard care sedation participants involves the administration of sedative medications to facilitate mechanical ventilation. Standard care in the SPICE III trial directs clinicians towards avoiding dexmedetomidine unless deemed clinically necessary. The SPICE III trial registration number is NCT01728558 (Trial from ClinicalTrials.gov). All data will be retrieved from the participants medical record and with the duration of the observation period to include the duration of ICU stay and hospital admission. Data will be collected from 1st November 2013 to 31st August 2015.
Control group
Historical

Outcomes
Primary outcome [1] 296192 0
Noradrenaline volume requirment during sedation to facilitate mechanical ventilation assessed by medical medical record review.
Timepoint [1] 296192 0
Daily during the ICU care
Secondary outcome [1] 317761 0
Continuous renal replacement therapy free days assessed via medical record review
Timepoint [1] 317761 0
Daily from ICU admission until ICU discharge
Secondary outcome [2] 317762 0
Mechanical ventilation free days assessed via medical record review
Timepoint [2] 317762 0
Daily from ICU admission until ICU discharge
Secondary outcome [3] 317763 0
Mortality - intensive care unit assessed via medical record review
Timepoint [3] 317763 0
Daily from ICU admission until ICU discharge
Secondary outcome [4] 317764 0
Mortality - hospital assessed via medical record review
Timepoint [4] 317764 0
Daily from hospital admission until hospital discharge

Eligibility
Key inclusion criteria
1. Aged 18 years or older
2. Subject has been intubated and is receiving mechanical ventilation
3. The treating clinician expects that the patient will remain intubated until the day after tomorrow (unlikely to be extubated the following day).
4. The patient requires immediate ongoing sedative medication for comfort, safety, and to facilitate the delivery of life support measures.
5. Documented site, or strong suspicion of infection with
6. 2 of the 4 clinical signs of inflammation (within the prior 24hours):
a) Core temperature greater than 38oC or less than 36oC
b) Heart rate greater than 90 bpm
c) Respiratory rate greater than 20 bpm, or PaCO2 less than 32 mmHg, or mechanical ventilation
d) White cell count greater than 12 x 109/L or less than 4 x 109/L or greater than 10% immature neutrophils
7. Treated with continuous vasopressors or inotropes to maintain a systolic blood pressure greater 90mmHg, or mean arterial blood pressure less than 60mmHg or a MAP target set by the treating clinician for maintaining perfusion
8. Administration of vasopressors or inotropes for greater than or equal to 4 hours and present at time of randomisation
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Age less than 18 years
2. Patient is pregnant and/or lactating
3. Has been intubated (excluding time spent intubated within an operating theatre or transport) for greater than 12 hours in an intensive care unit
4. Met all inclusion criteria more than 24 hours before study inclusion
5. Patients treated with etomidate
6. Proven or suspected acute primary brain lesion such as traumatic brain injury, intracranial haemorrhage, stroke, or hypoxic brain injury.
7. Proven or suspected spinal cord injury or other pathology that may result in permanent or prolonged weakness
8. Admission as a consequence of a suspected or proven drug overdose or burns.
9. Administration of ongoing neuromuscular blockade
10. Mean arterial blood (MAP) pressure that is less than 50 mmHg despite adequate resuscitation and vasopressor therapy at time of randomisation
11. 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
12. Known sensitivity to any of the study medications or the constituents of propofol (egg, soya or peanut protein)
13. Acute fulminant hepatic failure
14. Patient has been receiving full time residential nursing care.
15. 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.
16. Patient has an underlying disease that makes survival to 90 days unlikely

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Convenience sample
Timing
Retrospective
Statistical methods / analysis
All statistical analysis will be performed using STATA. We will perform descriptive and inferential statistics to help describe of participants. In addition, we will use simple statistical tests that will include comparisons using Chi-square tests for equal proportion with results reported as numbers, percentages (%), and 95% confidence intervals (CI). Continuously normally distributed variables will be compared using student t-tests and presented as means (95% CI). We plan to perform multivariable logistic regression analysis on all outcomes repeated measures ANOVA where applicable. A two-sided P-value < 0.05 was considered evidence of a significant difference in the study outcomes. Significance was set at 0.05 for all comparisons unless otherwise stated.

Based on previous studies, to detect a 30% difference in NA infusion rates between groups, with an expected standard deviation (SD) of 25% and a test power of the analysis of variance (ANOVA) of 80%, a sample size of 15 individuals per group will be required. To take into account the possibility of incomplete data recording, we will analyse 40 patients admitted to our intensive care unit.


Recruitment
Recruitment status
Active, not 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] 4384 0
Austin Health - Austin Hospital - Heidelberg

Funding & Sponsors
Funding source category [1] 292100 0
Hospital
Name [1] 292100 0
Austin Hospital, Austin Health
Address [1] 292100 0
145 Studley Road
Heidelberg, VIC 3084
Country [1] 292100 0
Australia
Primary sponsor type
Hospital
Name
Austin Hospital
Address
145 Studley Road
Heidelberg, VIC 3084
Country
Australia
Secondary sponsor category [1] 290778 0
Individual
Name [1] 290778 0
Professor Rinaldo Bellomo
Address [1] 290778 0
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg VIC 3084
Country [1] 290778 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293586 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 293586 0
Austin Health
c/o Austin Hospital
145 Studley Road
Heidelberg VIC 3084
Ethics committee country [1] 293586 0
Australia
Date submitted for ethics approval [1] 293586 0
Approval date [1] 293586 0
17/09/2015
Ethics approval number [1] 293586 0
LNR/15/Austin/391

Summary
Brief summary
Stabilizing the circulation of critically ill patients presenting with severe sepsis or septic can be complicated by a phenomenon called catecholamine hyposensitivity, which leads to a decreased effect of vasoactive drugs. Massive release of endogenous catecholamines like adrenaline and noradrenaline in the setting of sepsis can cause down-regulation and de-sensitization of alpha-1 receptors making the vasculature less responsive to catecholamines.

Interestingly, animal studies found that high doses of central alpha2-agonists like clonidine and dexmedetomidine increase vasopressor responsiveness in a septic shock model.

In view of the potentially deleterious effects of adrenergic overstimulation and receptor desensitization more research about the effect and use of alpha-2-agonists in clinical doses and critically ill patients is warranted.

In the critical care setting, the alpha-2-agonist clonidine has become an established drug for the management of conditions with a high sympathetic activity and it is also commonly used as a supplementary sedative agent. Dexmedetomidine has anaesthetic and analgesic properties and has much higher a2-receptor selectivity than clonidine. Like clonidine, dexmedetomidine is used for sedation in adult critically ill patients.

In view of the potential benefits of dexmedetomidine in septic patients, we aim to conduct a retrospective cohort study of the haemodynamic effect of dexmedetomidine compared to standard care sedation in septic patients admitted to the intensive care unit of the Austin Hospital.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 60562 0
Prof Rinaldo Bellomo
Address 60562 0
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg, VIC 3084
Country 60562 0
Australia
Phone 60562 0
+61 3 9496 5992
Fax 60562 0
+61 3 9496 3932
Email 60562 0
rinaldo.bellomo@austin.org.au
Contact person for public queries
Name 60563 0
A/Prof Glenn Eastwood
Address 60563 0
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg, VIC 3084
Country 60563 0
Australia
Phone 60563 0
+61 3 9496 4835
Fax 60563 0
+61 3 9496 3932
Email 60563 0
glenn.eastwood@austin.org.au
Contact person for scientific queries
Name 60564 0
Prof Rinaldo Bellomo
Address 60564 0
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg, VIC 3084
Country 60564 0
Australia
Phone 60564 0
+61 3 9496 5992
Fax 60564 0
+ 61 3 9496 3932
Email 60564 0
rinaldo.bellomo@austin.org.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary