Does Acetylsalicylic Acid Reduce the Mortality of Patients Admitted to an Intensive Care Unit

Study Overview
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Brief Summary
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Platelets play a central part not just in homeostasis and thrombosis as the primary effector cells, but they are also key cells in the regulation of the immunological response to various stressors. After activation, platelets release their granules which store different inflammatory mediators that induce coagulation, recruit further platelets, activate complement, attract neutrophils and leukocytes and regulate the vascular tone. Platelets activated by systemic inflammation and infection, may also contribute to the development of multiple organ failure. Thus, inhibition of platelet activation may have beneficial effects on critically ill patients. the investigators hypothesize that acetylsalicylic acid reduces the mortality of medical intensive care unit patients. In a retrospective study acetylsalicylic acid use was associated with a substantial reduction in a medical intensive care unit population (Winning et al., 2010). The investigators will conduct a randomized, double-blind study including 460 patients (2x230), who will be randomized to receive 100mg acetylsalicylic acid(daily, intravenous) or a placebo (0,9% sodium-choride solution) to assess whether acetylsalicylic acid reduces the mortality of medical intensive care unit patients. Main outcome criteria will be 28/90day-mortality. Furthermore the investigators will assess whether acetylsalicylic acid reduces the risk of suffering thromboembolic complications. Post-mortem examinations will be conducted in all patients who die in the course of the study. Furthermore we will assess bleeding rates, intensive care unit mortality and pharmacokinetic and pharmacodynamic properties of acetylsalicylic acid in the intensive care unit population.

Official Title
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Does Acetylsalicylic Acid Reduce the Mortality of Patients Admitted to an Intensive Care Unit

Conditions
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Critical Illness

Intervention / Treatment
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* Drug: Acetylsalicylic acid lysinate
* Drug: 0.9% sodium-chloride solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients admitted to an intensive care unit >18 years of age Exclusion Criteria: known allergy of intolerance to acetylsalicylic acid recent surgery or planned surgery active bleeding known coagulation disorders discretion of the physician terminal illness (anticipated life expectancy <3months; e.g. due to cancer) platelet count <20 000 recent ulcera recent gastrointestinal bleeding pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acetylsalicylic acid lysinate<br>100mg Acetylsalicylic Acid | Drug: Acetylsalicylic acid lysinate<br>* 100mg intravenously administered Acetylsalicylic Acid lysinate per day<br>|
| Placebo Comparator: 0.9% sodium-chloride solution<br>0.9% sodium-chloride solution | Drug: 0.9% sodium-chloride solution<br>* Placebo, intravenously administered, daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 28-day Mortality | Standard outcome measure of investigational intensive care unit trials. | 28-days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intensive Care Unit Mortality | Mortality of patients during their intensive care unit stay, 90 day mortality, potentially longer | up to 90 days after inclusion | 
| Number of Patients Who Developed a Thrombotic or Embolic Complications During the Trial | clinically relevant thromboembolic events assessed by standard care, potentially longer | average 28 days | 
| Bleeding Incidences | all bleeding incidence during the intensive care unit stay will be recorded. major bleeding criteria are taken from the Thrombolysis in myocardial infarction study (TIMI-Triton-38), potentially longer | average 28days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acetylsalicylic acid, intensive care unit, mortality, Post mortem examination, bleeding