Enhanced Firefighter Rehab Trial: The Role of Aspirin in Preventing Heat Stress Induced Platelet Activation

Study Overview
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Brief Summary
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The purpose of this study is to determine if aspirin taken by firefighters prevents platelets from becoming sticky when body temperature rises during work in protective clothing.

Detailed Description
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Firefighters have the highest rate of line-of duty death (LODD) in the United States. More than half of these LODD are cardiovascular related occurring disproportionately around fire suppression activities. In addition, shift work, lifestyle factors, and the exposures associated with fire suppression (e.g. smoke, chemicals) may predispose the firefighter to earlier onset of heart disease or cause a pro-inflammatory state leading to endothelial dysfunction. Fire suppression activities exacerbate cardiovascular strain and endothelial dysfunction and provide potential triggers for ischemic events (e.g. myocardial infarction, stroke). There is a rapid rise in heart rate following the activation of a fire company which may persist for as long as 20 minutes. Even in cases where heavy work is not being performed, the repetitive upper body exercise associated with tool use raises heart rate disproportionately to oxygen consumption. Finally, there is a rapid rise in core body temperature from increased physical activity, environmental heat and impaired thermoregulation that has been shown to cause vasoconstriction and activate coagulation during heat stress (12, 13). This has recently been demonstrated in firefighters working in thermal protective clothing. The combination of triggers created during fire suppression may result in heart attack or stroke, especially in firefighters with risk factors for cardiovascular disease. Interventions beyond basic fireground rehab may be required to minimize the effect of these triggers and enhance a firefighter's health and wellness. Fireground rehab typically focuses on cooling and rehydration of the firefighter following fire suppression or training with the assumption that these interventions will correct the underlying pathophysiology. Effective fireground rehab must deliver appropriate interventions and monitor the progress of the firefighter. While correcting hyperthermia and hypohydration are essential for continued performance, it is not clear if these therapies correct alterations in platelet or endothelial function or if other interventions are necessary to correct these physiological disturbances. Furthermore, the options for monitoring the firefighter beyond simply measuring heart and respiratory rate are limited. In our FEMA-funded Fireground Rehab Evaluation (FIRE) Trial, we demonstrated that five commercially available thermometers did not reliably measure or estimate core temperature following uncompensable heat stress (UHS) making it impossible to gauge the effectiveness of rehab interventions.

Official Title
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Enhanced Firefighter Rehab Trial: Aspirin Versus Placebo

Conditions
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Heat Stress Disorders

Intervention / Treatment
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* Drug: Daily aspirin (ASA)
* Other: Active cooling
* Drug: Acute aspirin (ASA)
* Other: Passive cooling
* Drug: Daily placebo
* Drug: Acute placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Apparently healthy males and females aged 18-49 years Exclusion Criteria: History of heart disease, vascular disease, or sudden death including prior MI, coronary revascularization, congenital heart disease or history of stroke Hypertension during screening: SBP>139 or DBP>89 Those who are taking medications that may be expected to blunt the physiologic response to a treadmill exercise test (e.g. beta blockers) Prescription medication with known side effect of impaired thermoregulation Positive pregnancy test at any time during the study Resting ECG with clinical presentation suggesting coronary heart disease (e.g. pathologic Q wave) Known history of gastrointestinal disease or disorder i.e. diverticulitis which creates a theoretical risk of the core temperature capsule becoming lodged in the digestive tract Medications and supplements known to alter endothelial function (e.g. arginine, omega 3 fatty acids, NSAIDS, tobacco products. This exclusion may be disregarded for subjects willing to stop taking the supplement for the duration of the study At the discretion of the study physician for any other medical condition or prescription medication Known history of platelet dysfunction Aspirin allergy or intolerance

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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All

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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Daily ASA, Active cool, Acute ASA<br>Two weeks of daily aspirin therapy prior to exercise, active cooling following exercise, aspirin immediately post exercise | Drug: Daily aspirin (ASA)<br>* Two weeks 82 mg aspirin taken orally prior to exercise protocol<br>Other: Active cooling<br>* Active cooling to remediate heat stress following exercise by placing hands and forearms into cold water<br>Drug: Acute aspirin (ASA)<br>* 325 mg chewable aspirin administered immediately following exercise<br>|
| Experimental: Daily ASA, Active cool, Acute placebo<br>Two weeks of daily aspirin therapy prior to exercise, active cooling following exercise, placebo immediately post exercise | Drug: Daily aspirin (ASA)<br>* Two weeks 82 mg aspirin taken orally prior to exercise protocol<br>Other: Active cooling<br>* Active cooling to remediate heat stress following exercise by placing hands and forearms into cold water<br>Drug: Acute placebo<br>* Placebo comparator for acute aspirin therapy<br>|
| Experimental: Daily ASA, Passive cool, Acute ASA<br>Two weeks of daily aspirin therapy prior to exercise, passive cooling following exercise, aspirin immediately post exercise | Drug: Daily aspirin (ASA)<br>* Two weeks 82 mg aspirin taken orally prior to exercise protocol<br>Drug: Acute aspirin (ASA)<br>* 325 mg chewable aspirin administered immediately following exercise<br>Other: Passive cooling<br>* Removing protective garments for passive cooling following exercise<br>|
| Experimental: Daily ASA, Passive cool, Acute placebo<br>Two weeks of daily aspirin therapy prior to exercise, passive cooling following exercise, placebo immediately post exercise | Drug: Daily aspirin (ASA)<br>* Two weeks 82 mg aspirin taken orally prior to exercise protocol<br>Other: Passive cooling<br>* Removing protective garments for passive cooling following exercise<br>Drug: Acute placebo<br>* Placebo comparator for acute aspirin therapy<br>|
| Experimental: Daily placebo, active cool, Acute ASA<br>Two weeks of daily placebo prior to exercise, active cooling following exercise, aspirin immediately post exercise | Other: Active cooling<br>* Active cooling to remediate heat stress following exercise by placing hands and forearms into cold water<br>Drug: Acute aspirin (ASA)<br>* 325 mg chewable aspirin administered immediately following exercise<br>Drug: Daily placebo<br>* Placebo comparator for daily aspirin therapy<br>|
| Experimental: Daily placebo, active cool, Acute placebo<br>Two weeks of daily placebo prior to exercise, active cooling following exercise, placebo immediately post exercise | Other: Active cooling<br>* Active cooling to remediate heat stress following exercise by placing hands and forearms into cold water<br>Drug: Daily placebo<br>* Placebo comparator for daily aspirin therapy<br>Drug: Acute placebo<br>* Placebo comparator for acute aspirin therapy<br>|
| Experimental: Daily placebo, Passive cool, Acute ASA<br>Two weeks of daily placebo prior to exercise, passive cooling following exercise, aspirin immediately post exercise | Drug: Acute aspirin (ASA)<br>* 325 mg chewable aspirin administered immediately following exercise<br>Other: Passive cooling<br>* Removing protective garments for passive cooling following exercise<br>Drug: Daily placebo<br>* Placebo comparator for daily aspirin therapy<br>|
| Placebo Comparator: Daily placebo, Passive cool, Acute placebo<br>Two weeks of daily placebo prior to exercise, passive cooling following exercise, placebo immediately post exercise | Other: Passive cooling<br>* Removing protective garments for passive cooling following exercise<br>Drug: Daily placebo<br>* Placebo comparator for daily aspirin therapy<br>Drug: Acute placebo<br>* Placebo comparator for acute aspirin therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Platelet Closure Time |  | 0, 30, 60, and 90 minutes post exercise | 
| Vascular Function Measured by Peripheral Arterial Tonometry | Reactive Hyperemia Index | Baseline, 30, 60, and 90 minutes post exercise | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Activation of Coagulation | This measure was not collected. Equipment was not available. | 0, 30, 60, and 90 minutes post exercise | 
| Hyperthermia and Hemoconcentration Identified by Retinal Imaging | This measure was not collected. Equipment was not available. | 0, 30, 60, and 90 minutes post exercise | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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aspirin, firefighter, heat stress, platelet activation