None listed
Conditions
Brief summary
When patients suffer infections or have damaged organs they may develop an excessive inflammatory response called the systemic inflammatory syndrome (SIRS). This SIRS manifests as changes in heart rate, breathing, white cells release into blood, fever and carbon dioxide production. While a small amount of SIRS may be helpful for the healing process, uncontrolled SIRS may contribute to making intensive care unit (ICU) patients unwell, leading to a low blood pressure, organ failure, need for artificial life support and, in some cases prolonged time in ICU and hospital and even death. Finding safe, effective and inexpensive ways to decrease the severity of SIRS is an important goal of modern ICU medicine. Unfortunately, no medications have been shown to do this. Recently, however, a safe drug used by millions of people every day has been shown to have unexpected properties that might reduce the severity of SIRS. This drug is Aspirin. Every day, Aspirin is given to millions of patients at low dose because it protects from heart attacks and strokes through its ability to block clotting. Over the last three to four years, however, multiple studies in animals and observational studies in man have shown that low-dose Aspirin (as given to patients with heart attacks and strokes) also inhibits excessive inflammation. Aspirin does this by stimulating the production of newly discovered helpful molecules called resolvins, protectins and maresins. These molecules combat inflammation and help the body to recover. Observational studies have reported that SIRS patients treated with Aspirin were more likely to live than similar untreated patients. In addition, patients who were on Aspirin before admission to ICU were similarly more likely to survive. On the other hand, it is also known that Aspirin therapy may increase the risk of bleeding, stomach inflammation and maybe even kidney impairment. How the risks and benefits of aspirin therapy balance each other in patients with SIRS is unknown because no controlled studies have been done so far. Because of this, we plan to conduct a pilot randomized controlled trial to study whether Aspirin treatment in patients with SIRS is safe, feasible, and shows preliminary evidence of beneficial effects. The primary outcome is the concentration of a substance which indicates severe inflammation, called interleukin 6 (IL-6) in the blood 48 hours after randomisation. We wish to test the hypothesis that Aspirin improves the resolution of high levels of IL-6. If our findings support the feasibility, safety and possible benficial effect of aspirin when used in this way, we will be able to conduct larger studies to asses its benefits in terms of patient-centred outcomes.
Interventions
Aspirin (100 mg twice daily) in the form of a soluble tablet given orally or by nasogastric tube from the time of enrollment following admission to the intensive care unit until discharge from the intensive care unit. Adherence with study protocol will be determined by the number of times the tablet was due to be administered compared with actually administered to the patient.
Sponsors
Austin Health
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Two or more of the follow critieria for the systemic inflammatory response sydrome (SIRS): a. Body temperature less than 36oC or greater than 38oC b. Heart rate greater than 90 beats per minute c. Tachypnea, with greater than 20 breaths per minute, or, an arterial partial pressure of carbon dioxide of less than 32 mmHg) or mechanically ventilated d. Leukocytes less than 4000 cells/mm3 (4 x 109 cells/L) or greater than 12,000 cells/mm3 (12 x 109 cells/L) or the presence or greater than 10% immature neutrophils (band forms).
Exclusion criteria
- Known allergic response to Aspirin - Severe thrombocytopenia (<75,000/mm3) - Pregnancy - Limitations of medical therapy - Intracranial haemorrhage - Ongoing bleeding - Any bleeding episode in the last 24 hours - Age <18 years - Surgery in the last 12 hours - Recent (< 3 months) diagnosis of gastric or duodenal ulcer - History of gastric or duodenal ulcer or upper gastrointestinal bleeding in the last 10 years - Prolonged International normalized ratio (INR) >2 - Prolonged activated partial thromboplastin time (APTT>50 seconds) - Any neurosurgery in the last 3 months - Patient is already on Aspirin for a specific indication (such as recent myocardial infarction of less than 12 months, recent cardiac stenting of less than 12 months or recent transient ischaemic attack of less than 12 months) - Death is expected within the next 24 hours - Any cardiac surgery (Aspirin is routinely prescribed)
Outcome results
None listed