Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12606000285550
Ethics application status
Approved
Date submitted
5/06/2006
Date registered
5/07/2006
Date last updated
6/11/2012
Type of registration
Retrospectively registered

Titles & IDs
Public title
The pharmacodynamics of unfractionated heparin and fondaparinux in critically ill patients with severe sepsis.
Scientific title
The pharmacodynamics of unfractionated heparin and fondaparinux in critically ill patients with severe sepsis.
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Critically ill patients with severe sepsis. 1260 0
Condition category
Condition code
Blood 1346 1346 0 0
Other blood disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a pharmacokinetic study to assess the bioavailability of heparin and fondaparinux (blood thinning agents) in Intensive care Unit (ICU) patients with sepsis. The bioavailability of these blood thinning agents will be measured by blood tests of the factor Xa inhibition during the 72 hour study period. Patients will be randomised to receive the three anticoagulant (blood thinning) regimens sequentially and have repeated tests of the inhibition of factor Xa activity.
The three heparin regimes to be assessed are:
1. Heparin 5000 Units administered subcutaneously twice daily.
2. Heparin 10 000 Units intravenously over 24 hours.
3. Fondaparinux 2.5 mg subcutaneously once daily.
Intervention code [1] 1125 0
Other interventions
Comparator / control treatment
No comparator.
Control group
Active

Outcomes
Primary outcome [1] 1836 0
To determine the bioavailability of heparin and fondaparinux in ICU patients with sepsis via factor Xa inhibition.
Timepoint [1] 1836 0
Factor Xa assays will be performed at 0, 1, 2, 3, 4, 8 and 12 hours after heparin is administered subcutaneously.
Factor Xa assays will be performed at 0, 1, 2, 3, 4, 8, 12, 18 and 24 hours during heparin intravenous infusion and at 0, 1, 2, 3, 4, 8, 12, 18 and 24 hours after fondaparinux subcutaneous administration.
Secondary outcome [1] 3218 0
Bleeding
Timepoint [1] 3218 0
Thrombotic complications will be monitored continuously throughout the 72 hour period and full coagulation parameters will be reviewed once daily.

Eligibility
Key inclusion criteria
1. Known or suspected severe sepsis at the time of screening and meet the inclusion criteria within the following 24 hours. 2. Diagnosis of severe sepsis, as defined in the recent Australian New Zealand Intensive Care Society Clinical Trials Group (ANZICS CTG) study of the incidence of severe sepsis in Australian and New Zealand ICUs [19]. The criteria for severe sepsis are the presence of systemic inflammatory response syndrome due to infection and the presence of organ dysfunction. a) Patients must have at least 3 of the following 4 criteria: 1. core temperature ³38oC or £36oC 2. heart rate ³90 beats/min unless known medical condition associated with increased heart rate or on medication that will prevent increased heart rate. 3. respiratory rate ³20 breaths/min or PaCO2 (partial pressure of carbon dioxide in arterial blood) 32 mmHg or receiving mechanical ventilation for acute respiratory failure. 4. white cell count ³12,000/mL or £4,000/mL or a differential count showing >10% immature neutrophils. PLUS One of the following six criteria must be present to confirm that the episode is due to infection: 1. polymorphonuclear cells in normally sterile site 2. culture of pathogenic organism from normally sterile site 3. chest x-ray changes consistent with pneumonia 4. focus of infection identified visually 5. underlying disease or condition known to be associated with infection (eg ascending cholangitis) 6. other (reason to be stated) PLUS Organ dysfunction entry criteria as described previously [19]. 4. Patients who consent or if the patient is incompetent, the next-of-kin who consent, to inclusion in the study.
Minimum age
18 Years
Maximum age
Not stated
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients will be excluded if, in the opinion or knowledge of the responsible clinician, any of the following criteria apply: 1. Patients aged less than 18 years. 2. Patient is receiving continued full anticoagulation treatment for another reason with either heparin or coumarin agents. 3. Patients with a contra-indication to low-dose heparin including intracranial haemorrhage, active bleeding, or Heparin induced Thrombcytopenia (HIT) in the past 3 months. 4. Patients with a prior adverse reaction to heparin. 5. Patients or next-of-kin do not consent to inclusion in the study.

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Sequentailly numbered opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
a computer generated randomisation matrix
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 4
Type of endpoint/s
Bio-availability
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/07/2006
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
15
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 1473 0
Hospital
Name [1] 1473 0
Royal Melbourne Hospital Intensive Care Unit
Country [1] 1473 0
Australia
Primary sponsor type
Individual
Name
Dr M Robertson
Address
Country
Secondary sponsor category [1] 1300 0
None
Name [1] 1300 0
nil
Address [1] 1300 0
Country [1] 1300 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 2855 0
Royal Melbourne Hospital
Ethics committee address [1] 2855 0
Ethics committee country [1] 2855 0
Date submitted for ethics approval [1] 2855 0
Approval date [1] 2855 0
Ethics approval number [1] 2855 0
2006.083

Summary
Brief summary
Given the significant incidence of deep venous thromboses (DVT) in critically ill patients and the failure of current prophylactic regimens to fully prevent DVT, additional pharmacokinetic information regarding the efficacy of heparin and fondaparinux in critically ill patients is required.
We aim to assess the bioavailability of heparin administered subcutaneously and intravenously and fondaparinux administered subcutaneously in a cohort of critically ill patients with severe sepsis.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 36269 0
Address 36269 0
Country 36269 0
Phone 36269 0
Fax 36269 0
Email 36269 0
Contact person for public queries
Name 10314 0
Belinda Howe- Research Co-ordinator
Address 10314 0
Intensive Care Unit (ICU)
Royal Melbourne Hospital
Grattan Street
Parkville VIC 3050
Country 10314 0
Australia
Phone 10314 0
+61 3 93427710
Fax 10314 0
+61 3 93428812
Email 10314 0
belinda.howe@mh.org.au
Contact person for scientific queries
Name 1242 0
Dr M Robertson-principal investigator
Address 1242 0
Intensive Care Unit (ICU)
Royal Melbourne Hospital
Grattan Street
Parkville VIC 3050
Country 1242 0
Australia
Phone 1242 0
+61 3 93427441
Fax 1242 0
+61 3 93428812
Email 1242 0
megan.robertson@mh.org.au

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

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