Effect of Aspirin on Hemostatic and Vascular Function After Live Fire Fighting

Study Overview
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Brief Summary
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The investigators hypothesize that an acute treatment of low-dose aspirin will lead to a) decreased resting platelet activation, platelet aggregation, and clotting potential, b) increased fibrinolytic potential following fire fighting, c) no significant effect on endothelial function or arterial stiffness versus the placebo condition. chronic treatment with low-dose aspirin will lead to a) decreased resting and fire fighting induced platelet activation, platelet aggregation, clotting potential, b) increased fibrinolytic potential, and c) increased endothelial function and decreased arterial stiffness in response to live fire fighting versus the placebo condition. short-term fire fighting activity will result in: a) a reduction in arterial function (reduced endothelial function, increased augmentation index and an attenuated arterial stiffness response); b) a disruption in hemostasis that is characterized by an increase in platelet number and function, an increased coagulatory potential and altered fibrinolytic potential; and c) an elevation in procoagulatory cytokines, systemic inflammation, monokine chemoattractant protein, and matrix metalloproteinases.

Official Title
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Effect of Aspirin on Hemostatic and Vascular Function After Live Fire Fighting

Conditions
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Cardiovascular Risk Factor, C.Medical Procedure; Vascular, Functional or Late, Electrolyte and Fluid Balance Conditions

Intervention / Treatment
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* Drug: 81 mg enteric coated aspirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male firefighters (career and volunteer), medically cleared by home fire department. Ages 40 - 60 Completion of a yearly period medical evaluation based on NFPA 1582 within the past 12 months or an evaluation by an occupational medical group through this study. Exclusion Criteria: Over 60 or under 40 years of age. Not a firefighter. Individuals at risk for developing gastrointestinal (GI) complications while on aspirin therapy due to a combination of the following: smoking; concurrent NSAID, steroid, Clopidogrel, or Warfarin therapy; history of upper GI complications; history of renal impairment; history of elevated serum creatinine; hypertension; and cardiac failure. Individuals with cases of allergy or asthma, intolerance, and recurrent vascular events. Individuals taking statins. Individuals who are currently taking aspiring regularly.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Acute, Aspirin<br>81 mg asprin provided 30 minutes prior to firefighting- Acute single dosage | Drug: 81 mg enteric coated aspirin<br>* 81 mg enteric coated aspirin will be provided both as an acute dosage immediately prior to firefighting (1 hour pre-activity) and as a 14 day dosage prior to firefighting<br>* Other names: aspirin;|
| Placebo Comparator: Acute, Placebo<br>Acute single dosage of placebo provided 30 minutes prior to firefighting | Drug: 81 mg enteric coated aspirin<br>* 81 mg enteric coated aspirin will be provided both as an acute dosage immediately prior to firefighting (1 hour pre-activity) and as a 14 day dosage prior to firefighting<br>* Other names: aspirin;|
| Active Comparator: Chronic, Aspirin<br>81 mg asprin provided prior to firefighting- 14 day dosage | Drug: 81 mg enteric coated aspirin<br>* 81 mg enteric coated aspirin will be provided both as an acute dosage immediately prior to firefighting (1 hour pre-activity) and as a 14 day dosage prior to firefighting<br>* Other names: aspirin;|
| Placebo Comparator: Chronic, Placebo<br>14 day dosage of placebo provided prior to firefighting | Drug: 81 mg enteric coated aspirin<br>* 81 mg enteric coated aspirin will be provided both as an acute dosage immediately prior to firefighting (1 hour pre-activity) and as a 14 day dosage prior to firefighting<br>* Other names: aspirin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vascular function | Vascular function will be assessed via pulse wave analysis, pulse wave velocity, carotid artery compliance, beta stiffness index, forearm rsistance artery vasodilatory capacity, and brachial artery blood flow. | Less than 60 minutes before initiating firefighting activity | 
| Hemostatic balance | Blood samples will be collected by a trained phlebotomist from the antecubital vein directly into vacutainers with little or no stasis using a 21-gauge needle. Samples will be used to quantify platetlet number and function, fibrinogen, prothrombin and partial thromboplastin time, t-PA and PAI-1 activities and antigen | Less than 60 minutes before initiating firefighting activity | 
| Inflammatory and Oxidative Stress markers | CRP,Intercellular adhesion molecule (ICAM)-1, IL-6, MMP-9, TIMP-1, TIMP-2,8-iso-prostaglandin F2a, soluble P-selectin | Less than 60 minutes before initiating firefighting activity | 
| Vascular function | Vascular function will be assessed via pulse wave analysis, pulse wave velocity, carotid artery compliance, beta stiffness index, forearm rsistance artery vasodilatory capacity, and brachial artery blood flow. | Less than 60 minutes after completing 20 minutes of firefighting activity | 
| Hemostatic balance | Blood samples will be collected by a trained phlebotomist from the antecubital vein directly into vacutainers with little or no stasis using a 21-gauge needle. Samples will be used to quantify platetlet number and function, fibrinogen, prothrombin and partial thromboplastin time, t-PA and PAI-1 activities and antigen | Less than 60 minutes after completing 20 minutes of firefighting activity | 
| Inflammatory and Oxidative Stress markers | CRP,Intercellular adhesion molecule (ICAM)-1, IL-6, MMP-9, TIMP-1, TIMP-2,8-iso-prostaglandin F2a, soluble P-selectin | Less than 60 minutes after completing 20 minutes of firefighting activity | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vascular function, Inflammation, Oxidative stress, Hemostatic balance, Aspirin, Firefighting