Critical Illness
Conditions
Keywords
acetylsalicylic acid, intensive care unit, mortality, Post mortem examination, bleeding
Brief summary
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.
Interventions
100mg intravenously administered Acetylsalicylic Acid lysinate per day
DRUG0.9% sodium-chloride solution
Placebo, intravenously administered, daily
Sponsors
Medical University of Vienna
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
double blind
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 28-day Mortality | 28-days | Standard outcome measure of investigational intensive care unit trials. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Intensive Care Unit Mortality | up to 90 days after inclusion | Mortality of patients during their intensive care unit stay, 90 day mortality, potentially longer |
| Number of Patients Who Developed a Thrombotic or Embolic Complications During the Trial | average 28 days | clinically relevant thromboembolic events assessed by standard care, potentially longer |
| Bleeding Incidences | average 28days | 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 |
Countries
Austria
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Acetylsalicylic Acid Lysinate 100mg Acetylsalicylic Acid
Acetylsalicylic acid lysinate: 100mg intravenously administered Acetylsalicylic Acid lysinate per day | 7 |
| 0.9% Sodium-chloride Solution 0.9% sodium-chloride solution
0.9% sodium-chloride solution: Placebo, intravenously administered, daily | 8 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | 0.9% Sodium-chloride Solution | Total | Acetylsalicylic Acid Lysinate |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 6 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 9 Participants | 5 Participants |
| Age, Continuous | 63 years STANDARD_DEVIATION 10 | 61 years STANDARD_DEVIATION 12 | 61 years STANDARD_DEVIATION 15 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment Austria | 8 participants | 15 participants | 7 participants |
| Sex: Female, Male Female | 2 Participants | 5 Participants | 3 Participants |
| Sex: Female, Male Male | 6 Participants | 10 Participants | 4 Participants |
| Simplified Acute Physiology Score III | 63 score on a scale STANDARD_DEVIATION 13 | 64 score on a scale STANDARD_DEVIATION 15 | 64 score on a scale STANDARD_DEVIATION 19 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 7 | 1 / 8 |
| other Total, other adverse events | 4 / 7 | 6 / 8 |
| serious Total, serious adverse events | 2 / 7 | 3 / 8 |
Outcome results
Primary
28-day Mortality
Standard outcome measure of investigational intensive care unit trials.
Time frame: 28-days
Population: modified Intention to treat population (all patients who received at least a single dose of acetylsalicylic acid)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Acetylsalicylic Acid Lysinate | 28-day Mortality | 1 participants |
| 0.9% Sodium-chloride Solution | 28-day Mortality | 1 participants |
p-value: 0.5795% CI: [0.039, 4.792]Chi-squared
Secondary
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
Time frame: average 28days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Acetylsalicylic Acid Lysinate | Bleeding Incidences | 1 counts |
| 0.9% Sodium-chloride Solution | Bleeding Incidences | 0 counts |
p-value: 0.467Chi-squared
Secondary
Intensive Care Unit Mortality
Mortality of patients during their intensive care unit stay, 90 day mortality, potentially longer
Time frame: up to 90 days after inclusion
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Acetylsalicylic Acid Lysinate | Intensive Care Unit Mortality | 2 participants |
| 0.9% Sodium-chloride Solution | Intensive Care Unit Mortality | 1 participants |
p-value: 0.057Chi-squared
Secondary
Number of Patients Who Developed a Thrombotic or Embolic Complications During the Trial
clinically relevant thromboembolic events assessed by standard care, potentially longer
Time frame: average 28 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Acetylsalicylic Acid Lysinate | Number of Patients Who Developed a Thrombotic or Embolic Complications During the Trial | 0 participants |
| 0.9% Sodium-chloride Solution | Number of Patients Who Developed a Thrombotic or Embolic Complications During the Trial | 1 participants |
p-value: 1Chi-squared