Healthy AdultsPhase 4SABSNCT07462715
Statins Against Bushfire Smoke
A Phase 4 study testing Atorvastatin in people with Healthy Adults, run by Menzies Institute for Medical Research at 1 site in Australia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 68 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Adults
- What is being tested?
- Atorvastatin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 1 siteAustralia
- Study dates
- 1 May 2026to 31 Dec 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 68 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Good general health and, if aged 45 year or more, low to intermediate (<10%) atherosclerotic cardiovascular disease (ASCVD) risk category, based on clinical data measured within 12 months prior to enrolment.
Who cannot join
- History of severe chronic lung diseases such as chronic obstructive pulmonary disease or asthma as determined by participants' care providers.
- History of chest pain, irregular heartbeats, heart failure, heart attack, heart pacemaker or coronary bypass surgery.
- High cardiovascular risk (>10%) category on the ASCVD risk calculator or judged to be at high risk by study cardiologist, for those aged 45 years or older.
- History of stroke, dementia or other neurological condition
- Untreated high blood pressure (≥ 140 systolic, ≥ 90 diastolic)
- History of autoimmune or inflammatory rheumatic disease (e.g., rheumatoid arthritis, systemic lupus erythematosus, spondyloarthritis). Osteoarthritis alone is not an exclusion.
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- History of immunodeficiency
- Diabetes (any type)
- Current medications: Long term medications that interact with atorvastatin (such as verapamil, digoxin and warfarin); Medications that affect heart rate variability including beta-blockers (such as atenolol, metoprolol, propranolol, and acebutolol), tricyclic antidepressants and selective serotonin reuptake inhibitors (such as amitriptyline, sertraline, fluoxetine or citalopram), or medications with anti-cholinergic action (such as promethazine or prochlorperazine); stimulant medications, such as those prescribed for ADHD (such as methylphenidate, dexamphetamine, lisdexamfetamine); anti-inflammatory, immunosuppressive or immune modulating medications including systemic corticosteroids (such as prednisolone, dexamethasone) and non-steroidal anti-inflammatory drugs (NSAIDS) (such as ibuprofen, naproxen or diclofenac)
- Currently smoking, or have smoked: more than one pack of cigarettes in the past year, or have smoked more than 100 packs of cigarettes in their lifetime
- Currently vaping or have vaped: more than 200 puffs in the last year, more than 20,000 puffs in their lifetime
- Currently pregnant, attempting to become pregnant or breastfeeding
- History of skin allergy to tape or electrodes
- Inability to travel to the study site
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Australia1 site
Menzies Institute for Medical Research
Hobart, Tasmania, 7000
Lieke Scheepers, PhD, +61 8 6226 4875, lieke.scheepers@utas.edu.au
Madeline Carins Murphy, PhD, Madeline.CarinsMurphy@utas.edu.au
About this study
Official title: 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.
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:
- 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?
- 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?
Read more
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.
Read the 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
- Being tested
- Atorvastatin, Placebo
- Keywords
- bushfire smoke, wildfire, air pollution, cardiovascular function, statin, inflamation, cognitive function
- Medical subject headings
- Pemphigus and fogo selvagem
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AtorvastatinDrug
Also called Another class of statin in those who do not tolerate 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.
PlaceboDrug
Identical placebo tablets to the atorvastatin tablets used in the intervention group
| Study group | Role | What they receive |
|---|---|---|
| Stream 1. Short term atorvastatin | Experimental | Participants randomly assigned to receive statin (80mg atorvastatin) to be taken in the morning the day before and on the morning of the exposure, 1 to 2 hours before each visit. Receives: Drug: Atorvastatin |
| Stream 1. Short term placebo | Placebo comparator | Participants randomly assigned to receive placebo tablets identical to the experimental arm, to be taken in the morning the day before and on the morning of the exposure, 1 to 2 hours before each visit. Receives: Drug: Placebo |
| Stream 2. Long term statin treatment | Active comparator | Long-term statin (stream 2): Participants in this study will have been taking a statin medication for at least one year. Receives: Drug: Atorvastatin |
| Stream 2. Statin naïve comparison group | No intervention | Long-term statin (stream 2): The comparison group will be statin naïve with comparable age gender and cardiovascular risk groupings. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in heart rate variability (HRV) associated with smoke exposure in the groups treated with statins, compared with the groups not treated with statins.
Heart rate variability measured as (1) Standard Deviation of Normal-to-Normal intervals (SDNN) and Root Mean Square of Successive Differences (RMSSD).
Measured: HRV is measured on two occasions at least 4 weeks apart, one with 2 hours of smoke exposure and one with 2 hours of filtered air exposure. The measurement is continuous over three hours including the half hour before and after the environmental exposure.
Secondary outcomes (13)
Change in blood pressure (BP) associated with smoke exposure in the group treated with statins, compared with the group not treated with statins.
Non invasive, ambulant brachial BP is measured using the ABPM-Pro. The first baseline measure is taken a rest with the third of three measures recorded. Thereafter results from a single measurement are recorded every 15 minutes.
Measured: BP is measured 15 minutely for 3 hours on two occasions at least 4 weeks apart. Once incorporating 2 hours of smoke exposure and once incorporating 2 hours of filtered air exposure.
Change in aortic vascular stiffness associated with smoke exposure in the group treated with statins, compared with the group not treated with statins.
Aortic vascular stiffness is asses by measuring pulse wave velocity (PWV). PWV from the carotid to the femoral artery is measured with a Sphygmo-cor device using with a carotid tonometer and a femoral BP cuff.
Measured: PWV is measured on two occasions at least 4 weeks apart, one immediately following 2 hours of smoke exposure and the other following 2 hours of filtered air exposure.
Difference in Oxidised Low-Density Lipoprotein (oxLDL) Levels Following Clean Air vs. Simulated Bushfire Smoke Exposure in Participants Treated with Statins Compared to Those Not Treated with Statins
Oxidised low-density lipoprotein (oxLDL) is a biomarker of oxidative stress and inflammation. Blood samples will be collected following each 2-hour exposure session (clean air and simulated bushfire smoke) to measure oxLDL levels. Changes in oxLDL between the clean air and simulated bushfire smoke conditions will be compared between participants currently treated with statins and those not treated with statins, to assess whether statin use modifies the oxidative stress response to bushfire smoke exposure.
Measured: Following each 2-hour exposure session (clean air and simulated bushfire smoke), with sessions separated by at least 4 weeks.
Difference in High-Sensitivity C-Reactive Protein (hsCRP) Levels Following Clean Air vs. Simulated Bushfire Smoke Exposure in Participants Treated with Statins Compared to Those Not Treated with Statins
High-sensitivity C-reactive protein (hsCRP) is a biomarker of systemic inflammation and oxidative stress. Blood samples will be collected following each 2-hour exposure session (clean air and simulated bushfire smoke) to measure hsCRP levels. Changes in hsCRP between the clean air and simulated bushfire smoke conditions will be compared between participants currently treated with statins and those not treated with statins, to assess whether statin use modifies the inflammatory response to bushfire smoke exposure. The two exposure sessions are separated by a minimum washout period of at least 4 weeks.
Measured: Following each 2-hour exposure session (clean air and simulated bushfire smoke), with sessions separated by at least 4 weeks.
Difference in Soluble Intercellular and Vascular Cell Adhesion Molecule Levels (sICAM-1 and sVCAM-1) Following Clean Air vs. Simulated Bushfire Smoke Exposure in Participants Treated with Statins Compared to Those Not Treated with Statins
Soluble intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) are biomarkers of vascular inflammation and endothelial activation. Blood samples will be collected following each 2-hour exposure session (clean air and simulated bushfire smoke) to measure sICAM-1 and sVCAM-1 levels. Changes in these markers between the clean air and simulated bushfire smoke conditions will be compared between participants currently treated with statins and those not treated with statins, to assess whether statin use modifies the vascular inflammatory response to bushfire smoke exposure. The two exposure sessions are separated by a minimum washout period of at least 4 weeks.
Measured: Following each 2-hour exposure session (clean air and simulated bushfire smoke), with sessions separated by at least 4 weeks.
Difference in Serum Amyloid A (SAA) Levels Following Clean Air vs. Simulated Bushfire Smoke Exposure in Participants Treated with Statins Compared to Those Not Treated with Statins.
Serum amyloid A (SAA) is a major acute-phase protein and highly sensitive biomarker of inflammation. Blood samples will be collected following each 2-hour exposure session (clean air and simulated bushfire smoke) to measure SAA levels. Changes in SAA between the clean air and simulated bushfire smoke conditions will be compared between participants currently treated with statins and those not treated with statins, to assess whether statin use modifies the acute-phase inflammatory response to bushfire smoke exposure. The two exposure sessions are separated by a minimum washout period of at least 4 weeks.
Measured: Following each 2-hour exposure session (clean air and simulated bushfire smoke), with sessions separated by at least 4 weeks
Spatial Working Memory Score as Assessed by the CANTAB Spatial Working Memory Test During Clean Air vs. Simulated Bushfire Smoke Exposure
Spatial working memory will be assessed using the CANTAB Spatial Working Memory (SWM) test, administered on a tablet during the second hour of each 2-hour exposure session. The test requires participants to search through boxes to find hidden tokens, measuring the ability to retain and manipulate spatial information. Outcome metrics include between-errors, strategy scores, and latency. Scores will be compared between the clean air and simulated bushfire smoke exposure sessions
Measured: During the second hour of each 2-hour exposure session (clean air and simulated bushfire smoke)
Cognitive Inhibition and Processing Speed Score as Assessed by the Modified Stroop Test During Clean Air vs. Simulated Bushfire Smoke Exposure
Cognitive inhibition and processing speed will be assessed using the modified Stroop test, administered on a laptop during the second hour of each 2-hour exposure session. Participants are required to identify ink colours while suppressing the reading of incongruent colour words. Outcome metrics include response accuracy and reaction time. Scores will be compared between the clean air and simulated bushfire smoke exposure sessions.
Measured: During the second hour of each 2-hour exposure session (clean air and simulated bushfire smoke)
Self-Reported Anxiety Score as Assessed by the State-Trait Anxiety Inventory (STAI) During Clean Air vs. Simulated Bushfire Smoke Exposure
Anxiety will be assessed using the State-Trait Anxiety Inventory (STAI), a validated self-report questionnaire completed during the second hour of each 2-hour exposure session. The STAI consists of two 20-item subscales measuring state anxiety (current feelings) and trait anxiety (general tendency). Each item is rated on a 4-point scale, with total scores ranging from 20 to 80 per subscale; higher scores indicate greater anxiety. Scores will be compared between the clean air and simulated bushfire smoke exposure sessions.
Measured: During the second hour of each 2-hour exposure session (clean air and simulated bushfire smoke)
Postural Stability as Assessed by a Standing Balance Test (Floor and Foam Surfaces, Eyes Open and Closed) During Clean Air vs. Simulated Bushfire Smoke Exposure
Postural stability will be assessed using a short standing balance test administered during the second hour of each 2-hour exposure session. Participants stand quietly at a comfortable foot width under four conditions: floor with eyes open, floor with eyes closed, foam with eyes open, and foam with eyes closed. Outcome metrics include sway and balance performance scores. Results will be compared between the clean air and simulated bushfire smoke exposure sessions
Measured: During the second hour of each 2-hour exposure session (clean air and simulated bushfire smoke)
Symptoms
Short survey (10 minutes) collecting information about muscular, respiratory and general health symptoms.
Measured: Collected immediately before and after environmental exposure sessions
Salivary cortisol
1 to 1.8 mls of saliva will be collected using the passive drool method for cortisol assay
Measured: Collected before and after each environmental exposure session
Urinary markers of oxidative stress
50ml of urine for measurement of 1-OH-NAP, 2-OH-NAP, and pyrene carboxylic acid
Measured: A total of three samples will be collected. Before and after each environmental exposure session and the first void urine the following morning.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2026
- Study start1 May 2026 (estimated)
- Primary completion30 Jun 2027 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy AdultsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This study has two streams. Each stream has a treatment arm and a comparison arm as described below. Stream 1 - Short-term statin treatment (2 days) Triple-blind, individually randomised treatment, parallel-group, placebo-controlled trial of statin, efficacy, with cross-over, order-randomised exposure 4 weeks apart. Stream 2 - Long-term statin treatment (at least one year) Double-blind, parallel-group, usual-care -controlled trial of statin efficacy, trial with cross-over, order-randomised exposure 4 weeks apart.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Menzies Institute for Medical Research
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Fay Johnston, University of Tasmania
- Investigators
- Fay Johnston, MD, PhD, Principal investigator, Menzies Institute for Medical Research, University of TasmaniaLieke Scheepers, PhD, Study director, Menzies Institute for Medical ResearchQuan Huynh, MD, PhD, Study director, Menzies Institute for Medical Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07462715
- Sponsor's protocol ID
- H40420
- Other IDs
- 2039822
- Acronym
- SABS
- Status last verified
- Mar 2026
- First submitted
- 27 Feb 2026
- Last updated
- 10 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data (IPD), including the analyzable dataset, will be made available to other researchers on a case-by-case basis following study completion and publication of primary results. Participant consent to share de-identified data with other investigators is obtained at the time of enrolment.
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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.
- ClinicalTrials.gov ID
- NCT07462715
- Acronym / sponsor ID
- SABS / H40420
- Conditions
- Healthy Adults
- Keywords
- bushfire smoke, wildfire, air pollution, cardiovascular function, statin, inflamation, cognitive function
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Menzies Institute for Medical ResearchUniversity, hospital or other
- Study start
- 1 May 2026 (estimated)
- Primary completion
- 30 Jun 2027 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 10 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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?
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- This study has two streams. Each stream has a treatment arm and a comparison arm as described below. Stream 1 - Short-term statin treatment (2 days) Triple-blind, individually randomised treatment, parallel-group, placebo-controlled trial of statin, efficacy, with cross-over, order-randomised exposure 4 weeks apart. Stream 2 - Long-term statin treatment (at least one year) Double-blind, parallel-group, usual-care -controlled trial of statin efficacy, trial with cross-over, order-randomised exposure 4 weeks apart.
| Arm | Type | Receives |
|---|---|---|
| Stream 1. Short term atorvastatin | Experimental | Drug: AtorvastatinParticipants randomly assigned to receive statin (80mg atorvastatin) to be taken in the morning the day before and on the morning of the exposure, 1 to 2 hours before each visit. |
| Stream 1. Short term placebo | Placebo comparator | Drug: PlaceboParticipants randomly assigned to receive placebo tablets identical to the experimental arm, to be taken in the morning the day before and on the morning of the exposure, 1 to 2 hours before each visit. |
| Stream 2. Long term statin treatment | Active comparator | Drug: AtorvastatinLong-term statin (stream 2): Participants in this study will have been taking a statin medication for at least one year. |
| Stream 2. Statin naïve comparison group | No intervention | –Long-term statin (stream 2): The comparison group will be statin naïve with comparable age gender and cardiovascular risk groupings. |
Who may qualify
- Ages
- 18 to 68 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Good general health and, if aged 45 year or more, low to intermediate (<10%) atherosclerotic cardiovascular disease (ASCVD) risk category, based on clinical data measured within 12 months prior to enrolment.
Key exclusion criteria (14 listed)
- History of severe chronic lung diseases such as chronic obstructive pulmonary disease or asthma as determined by participants' care providers.
- History of chest pain, irregular heartbeats, heart failure, heart attack, heart pacemaker or coronary bypass surgery.
- High cardiovascular risk (>10%) category on the ASCVD risk calculator or judged to be at high risk by study cardiologist, for those aged 45 years or older.
- History of stroke, dementia or other neurological condition
- Untreated high blood pressure (≥ 140 systolic, ≥ 90 diastolic)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AtorvastatinAlso: Another class of statin in those who do not tolerate atorvastatinStatin 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 | Stream 1. Short term atorvastatin, Stream 2. Long term statin treatment |
| PlaceboIdentical placebo tablets to the atorvastatin tablets used in the intervention group | Drug | Stream 1. Short term placebo |
Primary outcome
Change in heart rate variability (HRV) associated with smoke exposure in the groups treated with statins, compared with the groups not treated with statins.
Time frame: HRV is measured on two occasions at least 4 weeks apart, one with 2 hours of smoke exposure and one with 2 hours of filtered air exposure. The measurement is continuous over three hours including the half hour before and after the environmental exposure.
Heart rate variability measured as (1) Standard Deviation of Normal-to-Normal intervals (SDNN) and Root Mean Square of Successive Differences (RMSSD).
13 secondary outcomes
Change in blood pressure (BP) associated with smoke exposure in the group treated with statins, compared with the group not treated with statins.
Time frame: BP is measured 15 minutely for 3 hours on two occasions at least 4 weeks apart. Once incorporating 2 hours of smoke exposure and once incorporating 2 hours of filtered air exposure.
Change in aortic vascular stiffness associated with smoke exposure in the group treated with statins, compared with the group not treated with statins.
Time frame: PWV is measured on two occasions at least 4 weeks apart, one immediately following 2 hours of smoke exposure and the other following 2 hours of filtered air exposure.
Difference in Oxidised Low-Density Lipoprotein (oxLDL) Levels Following Clean Air vs. Simulated Bushfire Smoke Exposure in Participants Treated with Statins Compared to Those Not Treated with Statins
Time frame: Following each 2-hour exposure session (clean air and simulated bushfire smoke), with sessions separated by at least 4 weeks.
Difference in High-Sensitivity C-Reactive Protein (hsCRP) Levels Following Clean Air vs. Simulated Bushfire Smoke Exposure in Participants Treated with Statins Compared to Those Not Treated with Statins
Time frame: Following each 2-hour exposure session (clean air and simulated bushfire smoke), with sessions separated by at least 4 weeks.
Difference in Soluble Intercellular and Vascular Cell Adhesion Molecule Levels (sICAM-1 and sVCAM-1) Following Clean Air vs. Simulated Bushfire Smoke Exposure in Participants Treated with Statins Compared to Those Not Treated with Statins
Time frame: Following each 2-hour exposure session (clean air and simulated bushfire smoke), with sessions separated by at least 4 weeks.
Difference in Serum Amyloid A (SAA) Levels Following Clean Air vs. Simulated Bushfire Smoke Exposure in Participants Treated with Statins Compared to Those Not Treated with Statins.
Time frame: Following each 2-hour exposure session (clean air and simulated bushfire smoke), with sessions separated by at least 4 weeks
Spatial Working Memory Score as Assessed by the CANTAB Spatial Working Memory Test During Clean Air vs. Simulated Bushfire Smoke Exposure
Time frame: During the second hour of each 2-hour exposure session (clean air and simulated bushfire smoke)
Cognitive Inhibition and Processing Speed Score as Assessed by the Modified Stroop Test During Clean Air vs. Simulated Bushfire Smoke Exposure
Time frame: During the second hour of each 2-hour exposure session (clean air and simulated bushfire smoke)
Self-Reported Anxiety Score as Assessed by the State-Trait Anxiety Inventory (STAI) During Clean Air vs. Simulated Bushfire Smoke Exposure
Time frame: During the second hour of each 2-hour exposure session (clean air and simulated bushfire smoke)
Postural Stability as Assessed by a Standing Balance Test (Floor and Foam Surfaces, Eyes Open and Closed) During Clean Air vs. Simulated Bushfire Smoke Exposure
Time frame: During the second hour of each 2-hour exposure session (clean air and simulated bushfire smoke)
Symptoms
Time frame: Collected immediately before and after environmental exposure sessions
Salivary cortisol
Time frame: Collected before and after each environmental exposure session
Urinary markers of oxidative stress
Time frame: A total of three samples will be collected. Before and after each environmental exposure session and the first void urine the following morning.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2026.
- Individual participant dataSharing planned: Yes. De-identified individual participant data (IPD), including the analyzable dataset, will be made available to other researchers on a case-by-case basis following study completion and publication of primary results. Participant consent to share de-identified data with other investigators is obtained at the time of enrolment.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Fay Johnston, MD, PhD principal investigator
Menzies Institute for Medical Research, University of Tasmania
Lieke Scheepers, PhD study director
Menzies Institute for Medical Research
Quan Huynh, MD, PhD study director
Menzies Institute for Medical Research
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Atorvastatin in people with Healthy Adults, run by Menzies Institute for Medical Research at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 10 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Study coordinator (+61 8 6226 4875, sabs@utas.edu.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in heart rate variability (HRV) associated with smoke exposure in the groups treated with statins, compared with the groups not treated with statins. (time frame: HRV is measured on two occasions at least 4 weeks apart, one with 2 hours of smoke exposure and one with 2 hours of filtered air exposure. The measurement is continuous over three hours including the half hour before and after the environmental exposure.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2026.