The effects of acetylsalicylic acid on immunoparalysis following human endotoxemia

Completed

• Conditions: bacterial bloodstream infection; Sepsis; 10027665; 10004018

• Registration Number: NL-OMON43332
• Lead Sponsor: Radboud Universitair Medisch Centrum

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 23 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 30

Inclusion Criteria

- Written informed consent
- Age *18 and *35 yrs
- Male
- Healthy (as confirmed by medical history, examination, ECG, blood sampling)

Exclusion Criteria

* Use of any medication
* Use of COX inhibitors within 6 weeks prior to the first endotoxemia day
* Smoking
* Known anaphylaxis or hypersensitivity to acetylsalicylic acid or non-investigational products
* History or signs of atopic syndrome (asthma, rhinitis with medication and/or eczema)
* History of peptic ulcer disease
* History or signs of hematological disease
* Thrombocytopenia (<150*10^9/ml) or anemia (hemoglobin < 8.0 mmol/L)
* History of glucose-6-phospate dehydrogenase deficiency
* History of intracranial hemorrhage
* History, signs or symptoms of cardiovascular disease, in particular:
* Previous spontaneous vagal collapse
* History of atrial or ventricular arrhythmia
* Cardiac conduction abnormalities on the ECG consisting of a 2nd degree atrioventricular block or a complete left bundle branch block
* Hypertension (defined as RR systolic > 160 or RR diastolic > 90)
* Hypotension (defined as RR systolic < 100 or RR diastolic < 50)
* Renal impairment (defined as plasma creatinine >120 *mol/l)
* Liver enzyme abnormalities (above 2x the upper limit of normal)
* Medical history of any disease associated with immune deficiency
* CRP > 20 mg/L, WBC > 12x109/L or < 4 x109/L or clinically significant acute illness, including infections, within 4 weeks before the first endotoxemia day
* Previous (participation in a study with) LPS administration
* Participation in a drug trial or donation of blood 3 months prior to first endotoxemia day
* Any vaccination within 3 months prior to first endotoxemia day until the end of the study
* Recent hospital admission or surgery with general anesthesia (<3 months to endotoxemia day)
* Use of recreational drugs within 21 days prior to the first endotoxemia day
* Inability to personally provide written informed consent (e.g. for linguistic or mental reasons) and/or take part in the study

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary study endpoint, endotoxin tolerance, is the decrease in the area<br /><br>under the curve (AUC) of the plasma TNF* concentration between the first and<br /><br>second endotoxin challenge in the control group compared to the treatment<br /><br>group. </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>- Plasma levels of other inflammatory mediators on the first and second<br /><br>endotoxemia day (including but not limited to TNF*, IL-6, IL-8, IL-10, IL-1RA)<br /><br>- Ex vivo production of inflammatory mediators and reactive oxygen species<br /><br>(ROS) by whole blood and peripheral blood mononuclear cells (PBMCs) stimulated<br /><br>by LPS and several pathogens (including but not limited to S. aureus, M.<br /><br>tuberculosis, C. albicans)<br /><br>- Monocyte surface antigen expression (including but not limited to mHLA-DR,<br /><br>Programmed Death Ligand (PDL)-1, Programmed cell Death protein (PD)-1, IL-7R)<br /><br>- Plasma thromboxane B2 levels, as an expression of thromboxane A2<br /><br>- Prostaglandin E2 urine metabolites (PGE-M)<br /><br>- Kidney damage markers (including but not limited to NGAL, KIM-1, L-FABP)<br /><br>- Transcriptional activity of leukocytes<br /><br>- Symptom score<br /><br>- Mean arterial pressure<br /><br>- Heart rate<br /><br>- Temperature</p><br>