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Trial registered on ANZCTR


Registration number
ACTRN12611000649910
Ethics application status
Approved
Date submitted
22/06/2011
Date registered
24/06/2011
Date last updated
5/07/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Safe and effective use of aspirin in intensive care patients.
Scientific title
Randomised, open label, phase 1 study of aspirin in sepsis patients in ICU to determine the PK/PD of aspirin.
Secondary ID [1] 262432 0
Nil
Universal Trial Number (UTN)
U1111-1122-3666
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Sepsis 268124 0
Condition category
Condition code
Infection 268272 268272 0 0
Other infectious diseases
Inflammatory and Immune System 268285 268285 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Low doses of aspirin used in critically ill patients with sepsis or the systemic inflammatory response syndrome (SRS) being managed in the Intensive Care Unit.
Arm 1: 100 mg aspirin enterally via nasogastric tube, daily for two days
Arm 2: 300 mg aspirin enterally via nasogastric tube, daily for two days.
Arm 3: Control patients not treated with aspirin
Intervention code [1] 266806 0
Treatment: Drugs
Comparator / control treatment
This will be a dose finding and safety study. Patients will be randomised to receive aspirin in doses of 100 mg or 300 mg daily for two days or no therapy.
Control group
Active

Outcomes
Primary outcome [1] 268996 0
Pharmacokinetic and pharmacodynamic (PK/PD) modelling of the acetylsalicylic acid (ASA) and salicylic acid (SA) concentrations in SIRS/septic patients and relating them to their effect on immunological pathways caused by aspirin-triggered lipoxins (ATL) and NF-kappaB.
Timepoint [1] 268996 0
Ten mL of arterial blood will be taken immediately before (T 0) the first dose of aspirin (or at T0 in control patients not treated with aspirin) and after 1 hour (T 1), T 1.5, T 4, T 8, T 24, T 32, T 48.
Secondary outcome [1] 276773 0
Assessment of trends in clinical outcomes shown by sequential organ failure assessment (SOFA) score reductions in treated compared with control populations.
Timepoint [1] 276773 0
Daily measures for 2 days during study period.
Secondary outcome [2] 276774 0
Comparison of safety as measured by new onset bleeding or renal injury among aspirin and untreated disease controls in ICU patients with sepsis.
Timepoint [2] 276774 0
Continuous clinical observation during ICU stay for study period and further 3 days for new onset bleeding. Daily measure of urea and electrolytes for renal injury (increase by greater than factor of two in baseline creatinine) during study period.

Eligibility
Key inclusion criteria
Ninety critically ill adult patients over 18 years of age with SIRS or sepsis (infected site plus SIRS) will be enrolled having given informed consent. Study subjects will be required to have not taken aspirin in the 6 weeks prior to admission to ICU. An untreated control population consisting of 45 patients with SIRS or sepsis that are not treated with aspirin will be recruited and blood samples will be drawn to allow comparison of changes in PD parameters with aspirin treated patients.
Minimum age
18 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients with a contraindication to aspirin due to hypersensitivity to aspirin or NSAID drugs
platelet count <100,000×109/l
coagulopathy with INR>2 or active bleeding (eg, trauma, gastrointestinal or intracranial bleeding) will be excluded. Patients with pre-existing renal injury as per RIFLE guidelines will be excluded.
Patients will have study medications ceased if there is evidence of hypersensitivity to aspirin (new onset of severe bronchospasm or urticarial rash), renal injury (serum creatinine doubling / GFR reducing by > 50%) or new onset of bleeding.

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)
Randomised patients will have their study treatment allocated through opening a numbered envelope indicating dose of aspirin or no aspirin therapy control.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Study numbers will be divided into the three arms of the study by the use of a random number generator.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Pharmacokinetics / pharmacodynamics
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Data analysis is complete
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
1/08/2011
Actual
12/03/2012
Date of last participant enrolment
Anticipated
Actual
12/01/2015
Date of last data collection
Anticipated
Actual
2/02/2015
Sample size
Target
135
Accrual to date
Final
29
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 11319 0
The Townsville Hospital - Douglas

Funding & Sponsors
Funding source category [1] 267280 0
Government body
Name [1] 267280 0
National Health and Medical Research Council
Country [1] 267280 0
Australia
Primary sponsor type
Hospital
Name
Royal Melbourne Hospital
Address
Grattan St, Parkville, Victoria 3050
Country
Australia
Secondary sponsor category [1] 266362 0
None
Name [1] 266362 0
Address [1] 266362 0
Country [1] 266362 0
Other collaborator category [1] 252071 0
University
Name [1] 252071 0
University of Melbourne
Address [1] 252071 0
Department of Microbiology and Immunology
University of Melbourne
Parkville, Victoria, 3010
Country [1] 252071 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 269275 0
Melbourne Health Human Research Ethics Committee
Ethics committee address [1] 269275 0
Office for Research
Royal Melbourne Hospital
Grattan St
Parkville Victoria 3050
Ethics committee country [1] 269275 0
Australia
Date submitted for ethics approval [1] 269275 0
24/06/2011
Approval date [1] 269275 0
08/08/2011
Ethics approval number [1] 269275 0
2011.143

Summary
Brief summary
This proposal will examine the impact of aspirin on 15-epi-lipoxin A4 biosynthesis in severely ill patients for the first time. Low doses of aspirin have been clearly demonstrated to modulate this anti-inflammatory pathway. We will define the pharmacokinetics of low doses of aspirin in SIRS/sepsis patients providing critical information for future large-scale use of this agent in this population. Focusing on aspirin triggered lipoxins (ATL), we will explore the pharmacodynamics of low dose aspirin’s effects in SIRS/sepsis patients. This will extend previous measurements of beneficial impacts on nitric oxide, PMN apoptosis and TNF secretion by systematically analysing adaptive and innate immunological processes. The clinical trial is designed to be definitive and provide a clear answer on the basis with which to proceed to large-scale intervention trials.
Trial website
Trial related presentations / publications
PhD completion seminar Jacinta Ortega, RMIT
Public notes

Contacts
Principal investigator
Name 32766 0
A/Prof Damon Eisen
Address 32766 0
Victorian Infectious Diseases Service
792 Elizabeth St
Melbourne VIC 3000
Country 32766 0
Australia
Phone 32766 0
61 3 9342 9406
Fax 32766 0
Email 32766 0
[email protected]
Contact person for public queries
Name 16013 0
A/Prof Associate Professor Damon Eisen
Address 16013 0
Victorian Infectious Diseases Service
Royal Melbourne Hospital
Grattan St
Parkville, Victoria, 3050
Country 16013 0
Australia
Phone 16013 0
+61 3 9342 7212
Fax 16013 0
+61 3 9342 7277
Email 16013 0
[email protected]
Contact person for scientific queries
Name 6941 0
A/Prof Associate Professor Damon Eisen
Address 6941 0
Victorian Infectious Diseases Service
Royal Melbourne Hospital
Grattan St
Parkville, Victoria, 3050
Country 6941 0
Australia
Phone 6941 0
+61 3 9342 7212
Fax 6941 0
Email 6941 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
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