The Effect of Aspirin on REducing iNflammation in Human in Vivo Model of Acute Lung Injury (ARENA)

This is a double-blind, placebo-controled, randomized trial to investigate if aspirin pre-treatment has anti-inflammatory effects in a model of acute lung injury induced by inhaled endotoxin (LPS) in healthy human volunteers.

Study Overview

• Status: Completed
• Conditions: Acute Lung Injury
• Intervention / Treatment: Drug: Aspirin 75mg; Drug: Aspirin 1200mg; Drug: Lactose powder

• Study Type: Interventional
• Enrollment (Anticipated): 33
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • Belfast, United Kingdom
    • Belfast Health and Social Care Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy subjects

Exclusion Criteria:

• Age < 18 years
• Pregnancy or breast feeding or woman of childbearing potential not using
• adequate contraception.
• Participation in a clinical trial of an investigational medicinal product within 30 days
• Consent declined Aspirin or non steroidal anti-inflammatory (NSAID) use in the past 4 weeks
• History of asthma
• Known aspirin or NSAID hypersensitivity
• History of peptic ulcer disease
• Platelet count < 150 x 106/ml
• Aspirin resistance

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Aspirin 75mg; Aspirin 75mg once daily for 7 days. Administered by mouth.	Drug: Aspirin 75mg; Subjects randomised to aspirin 75mg will receive 1 container containing aspirin 75mg and 1 container containing placebo for the morning and 2 containers containing placebo for the evening. Subjects will take one capsule from each container in the morning and one capsule from each container in the evening.
Active Comparator: Aspirin 1200mg; Asprin 600mg twice daily for 7 days. Administered by mouth.	Drug: Aspirin 1200mg; Subjects randomised to aspirin 600mg 12 hourly will receive 2 containers of aspirin 300mg each for the morning and 2 containers of aspirin 300mg each for the evening. Subjects will take one capsule from each container in the morning and one capsule from each container in the evening.
Placebo Comparator: Lactose powder; Placebo for 7 days. Administered by mouth.	Drug: Lactose powder; Subjects randomised to placebo will receive 4 containers of placebo, 2 containers containing placebo for the morning and 2 containers containing placebo for the evening. Subjects will take one capsule from each container in the morning and one capsule from each container in the evening.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Bronchoalveolar lavage IL-8 concentration	6 hrs after LPS inhalation

Secondary Outcome Measures

Outcome Measure	Time Frame
Alveolar inflammatory response biomarkers	6 hrs after LPS inhalation
Plasma inflammatory response biomarkers	6 and 24 hrs after LPS inhalation
Alveolar epithelial and endothelial function and injury biomarkers	6 hrs after LPS inhalation
Lipid inflammatory mediators	6 and 24 hrs after LPS inhalation

Collaborators and Investigators

• Sponsor: Belfast Health and Social Care Trust
• Collaborators: Queen's University, Belfast; Northern Ireland Clinical Trials Unit; The Intensive Care Society United Kingdom
• Investigators: Principal Investigator: Danny McAuley, Queens University, Belfast

Publications and helpful links

General Publications

• Toner P, McAuley DF, Shyamsundar M. Aspirin as a potential treatment in sepsis or acute respiratory distress syndrome. Crit Care. 2015 Oct 23;19:374. doi: 10.1186/s13054-015-1091-6.
• Hamid U, Krasnodembskaya A, Fitzgerald M, Shyamsundar M, Kissenpfennig A, Scott C, Lefrancais E, Looney MR, Verghis R, Scott J, Simpson AJ, McNamee J, McAuley DF, O'Kane CM. Aspirin reduces lipopolysaccharide-induced pulmonary inflammation in human models of ARDS. Thorax. 2017 Nov;72(11):971-980. doi: 10.1136/thoraxjnl-2016-208571. Epub 2017 Jan 12.
• Curley GF, McAuley DF. Stem cells for respiratory failure. Curr Opin Crit Care. 2015 Feb;21(1):42-9. doi: 10.1097/MCC.0000000000000171.

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Actual): September 9, 2022
• Study Completion (Actual): September 9, 2022

Study Registration Dates

• First Submitted: August 4, 2012
• First Submitted That Met QC Criteria: August 4, 2012
• First Posted (Estimate): August 7, 2012

Study Record Updates

• Last Update Posted (Actual): September 13, 2022
• Last Update Submitted That Met QC Criteria: September 12, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Aspirin; Acute Respiratory Distress Syndrome; Acute Lung Injury
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Thoracic Injuries; Inflammation; Wounds and Injuries; Acute Lung Injury; Lung Injury; 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
• Other Study ID Numbers: 11127DMcA-AS; 2012-001589-13 (EudraCT Number)