NCT07462715

Statins Against Bushfire Smoke

Does Short-term or Long-term Statin Use Protect the Heart and Brain During Exposure to Bushfire Smoke? A Parallel-group Statin Trial With Cross-over, Order-randomised Smoke Exposure vs Filtered Air Among Healthy Australian Adults.

• Status: Not Yet Recruiting
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 100 (estimated)
• Sponsor: Menzies Institute for Medical Research · Academic / Other
• Sex: All
• Age: 18 Years – 68 Years
• Healthy volunteers: Accepted

Summary

The goal of this clinical trial is to test whether statins can protect the heart and brain from the biological stress and inflammatory responses caused by breathing bushfire smoke in healthy adult volunteers aged 18-64 years. The main questions it aims to answer are: 1. Does short-term statin use (2 days) reduce bushfire smoke-induced changes in heart rate variability, blood pressure, arterial stiffness, inflammation and oxidative stress markers, and cognitive function? 2. Does long-term statin use (≥12 months) reduce bushfire smoke-induced changes in heart rate variability, blood pressure, arterial stiffness, inflammation and oxidative stress markers, and cognitive function? The study includes two streams: Stream 1:short-term statin use (2 days) where participants receive either statin tablets (80mg atorvastatin) or placebo; Stream 2: long-term statin use (≥12 months) where participants include those already taking statins (≥12 months) with statin-naïve individuals. Participants will: * Attend two 3½-hour visits to a Climate Hut, which are approximately 4 weeks apart, where they will spend 2 hours exposed to either filtered air or simulated dilute bushfire smoke (average particulate matter (PM2.5) concentration of 300μg/m\^3) in randomised order; * Have continuous heart monitoring with ECG leads and blood pressure checks every 15 minutes during each visit * Provide urine, saliva, and nose swab samples before and after each exposure, plus follow-up samples the next morning * Complete cognitive tests (reaction time, memory tasks) and postural balance measurements during exposure * Complete questionnaires about anxiety levels, symptoms, diet, and health status * Have blood samples collected and pulse wave velocity measurements (assessing arterial stiffness) immediately after each exposure session. Potential risks include time commitment, muscle pain from statins, eye irritation or throat discomfort from smoke exposure, and minor discomfort from blood collection.

Detailed description

Background and Rationale: Climate-driven increases in landscape fire activity are substantially increasing population exposure to air pollution, the most important environmental driver of cardiovascular disease (CVD). The 2019-20 Australian bushfires exposed approximately 80% of the population to increased air pollution for several months, resulting in an estimated 429 excess deaths, 3,230 extra hospitalizations for cardiorespiratory problems, and 1,323 emergency presentations for asthma. Despite strong evidence linking air pollution to adverse cardiovascular outcomes, no intervention has been proven effective against bushfire smoke exposure in individuals. Oxidative stress, inflammation, and autonomic dysregulation are key mechanisms underlying these effects. Statins, beyond their cholesterol-lowering properties, have autonomic stabilizing, anti-inflammatory and antioxidant activity that may protect against cardiovascular impacts of air pollution. However, no clinical trials have tested this hypothesis. Exposure Methodology: The study utilizes the Climate Hut, a purpose-built facility at the University of Tasmania that allows controlled manipulation of air quality, temperature and humidity. The facility contains a small internal room with one transparent wall enabling observation and communication. Bushfire smoke is generated from eucalyptus fuel burned in a controlled combustion chamber, then diluted and delivered to maintain an average PM2.5 concentration of 300 μg/m³ during 2-hour exposure sessions. This concentration simulates community exposure during planned burns or bushfires and is comparable to smoke experienced at outdoor events with open fire heating. Filtered air sessions use HEPA filtration to remove particulate matter. Real-time monitoring of PM2.5, temperature, and humidity ensures consistent exposure conditions. Each participant undergoes both exposure conditions in randomized order, separated by ≥3 weeks washout period. Intervention Protocol: Stream 1 participants are randomized 1:1 to receive atorvastatin 80mg (supplied as two 40mg tablets) or identical placebo. The investigational product is supplied by SYNTRO Health in individual HDPE bottles containing 8 tablets per participant. Participants take 2 tablets on the morning of the day before each exposure visit and 2 tablets 1-2 hours before each exposure session. Stream 2 intervention group consists of participants who have been taking statin medication (primarily atorvastatin 40mg daily, or alternatives if myalgia occurred) for ≥12 months as part of the CAUGHT-CAD clinical trial or usual clinical care. The comparison group comprises statin-naïve individuals matched for age, sex, and cardiovascular risk profile. Technical Measurements: Heart rate variability is assessed through continuous 3-lead ECG monitoring (AMBPPro Research, Machinery Forum Medical Systems) throughout each 2-hour exposure. Time-domain measures (SDNN, RMSSD) and frequency-domain measures are calculated. Blood pressure is measured at 15-minute intervals using oscillometric monitoring. Pulse wave velocity is measured non-invasively using applanation tonometry (SphygmoCor, Atcor Medical) to assess carotid-femoral arterial stiffness pre- and post-exposure. Serum biomarkers including oxidized LDL, C-reactive protein, soluble ICAM-1 and VCAM-1, and serum amyloid A are quantified using multiplex protein assays (Abcam). Exploratory analyses include respiratory tract microbiome composition via 16S rRNA gene sequencing from nasopharyngeal swabs and urinary metabolites of PAH exposure (hydroxynaphthalenes, pyrene carboxylic acid) measured by LC-MS/MS. Safety Monitoring: Continuous ECG and regular blood pressure monitoring throughout exposure sessions enable real-time detection of cardiovascular changes. A study cardiologist (Prof Tom Marwick) is on-call for any medical concerns during exposure visits. An independent Medical Monitor (a cardiologist from the local hospital in Hobart) provides oversight of all adverse events. Pre-defined stopping criteria include sustained symptomatic tachycardia, bradycardia, arrhythmias, or blood pressure elevation requiring intervention. Participants are actively monitored for adverse events before, during, and immediately after exposure sessions, with passive collection continuing for 4 weeks post-exposure. Sample Size and Analysis: Each stream enrolls 50 participants (25 per treatment arm), providing 80% power to detect moderate effect sizes in the primary outcome (HRV changes) with α=0.05. Linear mixed-effects models will account for the crossover design, with each participant serving as their own control across exposure conditions. The primary comparison tests whether statin treatment modifies the change in HRV between filtered air and smoke exposure.

Conditions

• Healthy Adults

Interventions

Type	Name	Description
DRUG	Atorvastatin	Statin treatment is being investigated to see if it will modify subclinical adverse cardiovascular effects of bushfire smoke. Controlled dilute bushfire smoke is delivered on two occasions 4 weeks apart in a specialist facility. It is order randomised and masked.
DRUG	Placebo	Identical placebo tablets to the atorvastatin tablets used in the intervention group

Timeline

• Start date: 2026-05-01
• Primary completion: 2027-06-30
• Completion: 2028-12-31
• First posted: 2026-03-10
• Last updated: 2026-03-10

Locations

1 site across 1 country: Australia