The pharmacodynamics of unfractionated heparin and fondaparinux in critically ill patients with severe sepsis.

Phase 4

• Conditions: Critically ill patients with severe sepsis.; Blood - Other blood disorders

• Registration Number: ACTRN12606000285550
• Lead Sponsor: Dr M Robertson

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2006-07-05
• Last Update Posted: 13 January 2020

Recruitment & Eligibility

• Status: ot yet recruiting
• Sex: All
• Target Recruitment: 15

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.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To determine the bioavailability of heparin and fondaparinux in ICU patients with sepsis via factor Xa inhibition.[Factor Xa assays will be performed at 0, 1, 2, 3, 4, 8 and 12 hours after heparin is administered subcutaneously.<br>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 Measures

Name	Time	Method
Bleeding[Thrombotic complications will be monitored continuously throughout the 72 hour period and full coagulation parameters will be reviewed once daily.]