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

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.

Study Overview

• Status: Terminated
• Conditions: Critical Illness
• Intervention / Treatment: Drug: Acetylsalicylic acid lysinate; Drug: 0.9% sodium-chloride solution

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Medical University of Vienna
• Investigators: Principal Investigator: Bernd Jilma, Ao. Univ.-Prof. Dr. med, Medical University of Vienna, Department of Clinical Pharmacology

Publications and helpful links

General Publications

• Winning J, Neumann J, Kohl M, Claus RA, Reinhart K, Bauer M, Losche W. Antiplatelet drugs and outcome in mixed admissions to an intensive care unit. Crit Care Med. 2010 Jan;38(1):32-7. doi: 10.1097/CCM.0b013e3181b4275c.

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2011
• Primary Completion (Actual): September 5, 2017
• Study Completion (Actual): November 10, 2017

Study Registration Dates

• First Submitted: October 24, 2012
• First Submitted That Met QC Criteria: November 4, 2014
• First Posted (Estimate): November 6, 2014

Study Record Updates

• Last Update Posted (Actual): December 18, 2019
• Last Update Submitted That Met QC Criteria: November 28, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: intensive care unit; bleeding; mortality; acetylsalicylic acid; Post mortem examination
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Critical Illness; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Aspirin; Acetylsalicylic acid lysinate
• Other Study ID Numbers: ASA-MORT; 2012-002235-29 (EudraCT Number)