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Trial registered on ANZCTR


Registration number
ACTRN12613000784718
Ethics application status
Approved
Date submitted
12/07/2013
Date registered
15/07/2013
Date last updated
22/01/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
Relationship between peak temperature and survival of neutropenic sepsis in intensive care
Scientific title
In patients in intensive care units with neutropenic sepsis, is there an association between peak temperature within the first 24 hours and in-hospital mortality?
Secondary ID [1] 282773 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neutropenic sepsis 289524 0
Febrile neutropenia 289525 0
Haematological malignancy 289590 0
Condition category
Condition code
Infection 289849 289849 0 0
Other infectious diseases
Cancer 289850 289850 0 0
Any cancer
Blood 289851 289851 0 0
Other blood disorders

Intervention/exposure
Study type
Observational
Patient registry
True
Target follow-up duration
3
Target follow-up type
Months
Description of intervention(s) / exposure
This is an observational study. The condition observed is peak temperature, as recorded in the ANZICS-APD database, within the first 24 hours in the intensive care unit.
Intervention code [1] 287441 0
Not applicable
Comparator / control treatment
A contemporaneous cohort of patients with non-neutropenic sepsis.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 289912 0
In-hospital mortality, adjusted for illness severity by APACHE III risk of death (excluding temperature), and classified according to peak documented temperature during the first 24 hours following admission to the intensive care unit.
Timepoint [1] 289912 0
During inpatient episode. No censoring is applied. Patients for whom inpatient survival data are not available at the time of analysis will be excluded.
Secondary outcome [1] 303560 0
ICU length of stay, adjusted for illness severity by APACHE III risk of death (excluding temperature)
Timepoint [1] 303560 0
During inpatient episode. No censoring is applied. Patients for whom inpatient survival data are not available at the time of analysis will be excluded.

Eligibility
Key inclusion criteria
All patients admitted to an adult ICU at one of 157 centres in Australia and New Zealand between 2005 and 2013 for whom information is available on the Australian and New Zealand Intensive Care Society (ANZICS) Adult Patient Database (APD).

"Neutropenic sepsis" cohort:
White cell count equal to or less than 1.0 x10^9/L within the first 24 hours on the intensive care unit
APACHE-II diagnostic code indicating infection or haematological malignancy

"Neutropenic sepsis with haematological malignancy" cohort:
White cell count equal to or less than 1.0 x10^9/L within the first 24 hours on the intensive care unit
APACHE-II diagnostic or comorbidity code indicating haematological malignancy

"Non-neutropenic sepsis" cohort:
White cell count greater than or equal to 4.0 x10^9/L during the first 24 hours on the intensive care unit
APACHE-II diagnostic code indicating infection
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
No recorded white cell count during first 24 hours on intensive care unit
No recorded temperature during first 24 hours on intensive care unit

For "Non-neutropenic sepsis" cohort only:
APACHE-II diagnostic code or comorbidity code indicating a haematological malignancy

Study design
Purpose
Natural history
Duration
Cross-sectional
Selection
Defined population
Timing
Retrospective
Statistical methods / analysis
We will consider temperature as a categorical variable, divided into the following groups, according to peak temperature during the first 24 hours:
< 36.5 degrees Celsius (‘low temperature’)
36.5 degrees Celsius to 37.5 degrees Celsius (normothermia)
37.6 to 39.4 degrees Celsius (‘fever’)
>= 39.5 degrees Celsius (‘high fever’)

We will calculate odds ratios (95% CI) for the risk of in-hospital mortality associated with peak temperature for all patients. We will perform multivariate analysis using logistic regression adjusting for the patient’s severity of illness (by APACHE III score excluding temperature). To establish if the relationship between temperature and hospital mortality differs between we will fit an interaction between temperature and the individual subgroups.

We shall undertake a sensitivity analysis for ‘admitted to ICU on day of hospital admission’ versus ‘admitted to ICU after the day of hospital admission’.

Continuous variables will be presented as mean +/- standard deviation (SD) and median +/- interquartile range [IQR] for parametric and non-parametric data, respectively. We will report categorical variables as counts and percentages. A two-sided p-value of 0.05 will be considered to be statistically significant.

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)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC
Recruitment outside Australia
Country [1] 5166 0
New Zealand
State/province [1] 5166 0

Funding & Sponsors
Funding source category [1] 287541 0
Self funded/Unfunded
Name [1] 287541 0
Not relevant - unfunded
Address [1] 287541 0
Not relevant - unfunded
Country [1] 287541 0
Primary sponsor type
Individual
Name
Dr Robert Weinkove
Address
Wellington Blood & Cancer Centre
Capital & Coast District Health Board
Private Bag 7902
Wellington 6242
Country
New Zealand
Secondary sponsor category [1] 286294 0
None
Name [1] 286294 0
Address [1] 286294 0
Country [1] 286294 0
Other collaborator category [1] 277512 0
Individual
Name [1] 277512 0
Dr Paul Young
Address [1] 277512 0
Intensive Care Unit
Wellington Hospital
Private Bag 7902
Wellington 6242
Country [1] 277512 0
New Zealand
Other collaborator category [2] 277513 0
Individual
Name [2] 277513 0
A/Prof David Pilcher
Address [2] 277513 0
ICU The Alfred
Commerical Road
PRAHRAN VIC 3161
Country [2] 277513 0
Australia
Other collaborator category [3] 277514 0
Individual
Name [3] 277514 0
Dr Constantine Tam
Address [3] 277514 0
Peter MacCallum Cancer Centre
Locked Bag 1
A'Beckett Street
VIC 8006
Country [3] 277514 0
Australia
Other collaborator category [4] 277515 0
Individual
Name [4] 277515 0
Professor Richard Beasley
Address [4] 277515 0
Medical Research Institute of New Zealand
Private Bag 7902
Wellington 6242
Country [4] 277515 0
New Zealand
Other collaborator category [5] 277516 0
Individual
Name [5] 277516 0
Manoj Saxena
Address [5] 277516 0
The George Institute for Global Health
Level 13, 321 Kent St
Sydney NSW 2000
Country [5] 277516 0
Australia
Other collaborator category [6] 277517 0
Individual
Name [6] 277517 0
Assoc Prof Michael Bailey
Address [6] 277517 0
Epidemiology & Preventative Medicine
Monash Medical School Building
The Alfred Hospital
PO Box 315
Prahran VIC 3181
Country [6] 277517 0
Australia
Other collaborator category [7] 277518 0
Individual
Name [7] 277518 0
Professor Rinaldo Bellomo
Address [7] 277518 0
Epidemiology & Preventative Medicine
Monash Medical School Building
The Alfred Hospital
PO Box 315
Prahran VIC 3181
Country [7] 277518 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289522 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 289522 0
The Alfred Hospital,
55 Commercial Road,
Melbourne,
Victoria 3004
Ethics committee country [1] 289522 0
Australia
Date submitted for ethics approval [1] 289522 0
19/07/2013
Approval date [1] 289522 0
22/07/2013
Ethics approval number [1] 289522 0
333/13

Summary
Brief summary
In patients in intensive care with severe infections, those who do not develop a fever during the first 24 hours are more likely to die. This study aims to find out whether this is also the case in patients with infections in the absence of functioning white blood cells ('neutropenic sepsis'). We will look at a database of patients who were in intensive care in Australia and New Zealand between 2000 and 2013, to see whether there is a link between peak fever during the first 24 hours and survival among patients with very low white blood cell counts, compared with those with normal white blood cell counts. This study will inform the development of future clinical trials to decide whether the common medical practice of reducing fever during severe infections is harmful or not.
Trial website
Trial related presentations / publications
Association between early peak temperature and mortality in neutropenic sepsis. Weinkove R, Bailey M, Bellomo R, Saxena MK, Tam CS, Pilcher DV, Beasley R, Young PJ. Ann Hematol. 2014 Dec 18. [Epub ahead of print] PMID: 25516454
Public notes
The Quality Assurance Legislation of the Commonwealth of Australia (Part VC Health Insurance Act 1973, Commonwealth of Australia) allows use of data for research purposes without individual patient consent or specific ethical approval.

In New Zealand, this use of anonymous use of data for outcome analysis is classified as a ‘minimal risk’ observational study, and is exempt from requirements for formal ethics approval.

The ANZICS Centre for Outcome and Resource Evaluation (CORE) Management Committee have reviewed this protocol.

Contacts
Principal investigator
Name 41174 0
Dr Robert Weinkove
Address 41174 0
Wellington Blood & Cancer Centre
Capital & Coast District Health Board
Private Bag 7902
Wellington 6242
Country 41174 0
New Zealand
Phone 41174 0
+64221746400
Fax 41174 0
Email 41174 0
Robert.Weinkove@ccdhb.org.nz
Contact person for public queries
Name 41175 0
Dr Robert Weinkove
Address 41175 0
Wellington Blood & Cancer Centre
Capital & Coast District Health Board
Private Bag 7902
Wellington 6242
Country 41175 0
New Zealand
Phone 41175 0
+6443855999
Fax 41175 0
Email 41175 0
Robert.Weinkove@ccdhb.org.nz
Contact person for scientific queries
Name 41176 0
Dr Robert Weinkove
Address 41176 0
Wellington Blood & Cancer Centre
Capital & Coast District Health Board
Private Bag 7902
Wellington 6242
Country 41176 0
New Zealand
Phone 41176 0
+6443855999
Fax 41176 0
Email 41176 0
Robert.Weinkove@ccdhb.org.nz

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