None listed
Conditions
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.
Interventions
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 reg
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.
Sponsors
Dr M Robertson
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Diagnosis
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
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.
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.
Outcome results
None listed