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

Enhanced Firefighter Rehab Trial: Aspirin Versus Placebo

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.

Study Overview

• Status: Completed
• Conditions: Heat Stress Disorders
• Intervention / Treatment: Drug: Daily aspirin (ASA); Other: Active cooling; Drug: Acute aspirin (ASA); Drug: Acute placebo; Other: Passive cooling; Drug: Daily placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 124
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh, Emergency Responder Human Performance Lab

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Apparently healthy males and females aged 18-49 years

Exclusion Criteria:

1. History of heart disease, vascular disease, or sudden death including prior MI, coronary revascularization, congenital heart disease or history of stroke
2. Hypertension during screening: SBP>139 or DBP>89
3. Those who are taking medications that may be expected to blunt the physiologic response to a treadmill exercise test (e.g. beta blockers)
4. Prescription medication with known side effect of impaired thermoregulation
5. Positive pregnancy test at any time during the study
6. Resting ECG with clinical presentation suggesting coronary heart disease (e.g. pathologic Q wave)
7. 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
8. 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
9. At the discretion of the study physician for any other medical condition or prescription medication
10. Known history of platelet dysfunction
11. Aspirin allergy or intolerance

Study Plan

How is the study designed?

Design Details

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

Number of Arms

8

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Dave Hostler
• Collaborators: Federal Emergency Management Administration; Eyemarker Systems, Inc
• Investigators: Principal Investigator: David Hostler, PhD, University of Pittsburgh

Publications and helpful links

General Publications

• Olafiranye O, Hostler D, Winger DG, Wang L, Reis SE. Effect of aspirin on acute changes in peripheral arterial stiffness and endothelial function following exertional heat stress in firefighters: The factorial group results of the Enhanced Firefighter Rehab Trial. Vasc Med. 2015 Jun;20(3):230-6. doi: 10.1177/1358863X15571447. Epub 2015 May 4.
• Hostler D, Suyama J, Guyette FX, Moore CG, Pryor RR, Khorana P, McEntire SJ, Comer D, Reis SE. A randomized controlled trial of aspirin and exertional heat stress activation of platelets in firefighters during exertion in thermal protective clothing. Prehosp Emerg Care. 2014 Jul-Sep;18(3):359-67. doi: 10.3109/10903127.2013.869644. Epub 2014 Feb 18.

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Actual): June 1, 2011
• Study Completion (Actual): June 1, 2011

Study Registration Dates

• First Submitted: February 5, 2010
• First Submitted That Met QC Criteria: February 9, 2010
• First Posted (Estimate): February 10, 2010

Study Record Updates

• Last Update Posted (Actual): November 13, 2017
• Last Update Submitted That Met QC Criteria: October 10, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: aspirin; platelet activation; firefighter; heat stress
• Additional Relevant MeSH Terms: Wounds and Injuries; Heat Stress Disorders; 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: EMW-2008-FP-01638

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Study Data/Documents

1. Clinical Study Report
   Information comments: Report of vascular function testing
2. Clinical Study Report
   Information comments: Report of platelet function and physiology