TerminatedPhase 1ACTRN12611000649910

Safe and effective use of aspirin in intensive care patients.

Randomised, open label, phase 1 study of aspirin in sepsis patients in ICU to determine the PK/PD of aspirin.

Sponsor

Royal Melbourne Hospital

Enrollment

135 participants

Start Date

Mar 12, 2012

Study Type

Interventional

Conditions

Sepsis

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.

Eligibility

Sex: Both males and femalesMin Age: 18 YearssMax Age: 85 Yearss

Inclusion Criteria1

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.

Exclusion Criteria4

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.

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Interventions

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 nas

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