Altitude EdemaPhase 1/2SWIFTARCNCT06040268
Advair HFA in Healthy and HAPE Predisposed Subjects
A Phase 1/2 study testing Advair HFA in people with Altitude Edema, run by University of Colorado, Denver at 1 site in United States.
Trial summary
The current protocol is composed of two studies. The first study is designed to carefully evaluate the safety of high-dose salmeterol/fluticasone (Advair HFA) versus placebo (hydrofluoroalkane, HFA) administration over 7 days, as well as the efficacy of the study drug to increase exercise performance, in healthy… Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Altitude Edema
- What is being tested?
- Advair HFA
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Dec 2023to 15 Dec 2026
- Phase
- Phase 1/2
- 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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Written informed consent signed prior to entry into the study.
- Male or female age 18-50 years of age
- BMI ≥ 20 and < 35 kg/m2
- Agreement to comply with the study-required interventions and treatment during the full duration of the study.
- In good health as determined by screening medical history, physical examination, vital signs (blood pressure, heart rate, respiratory rate and temperature), clinical laboratory tests (CBC, protime (PT) (INR)/partial thromboplastin time (PTT), thyroid stimulating hormone (TSH), Total Bilirubin, blood chemistries, urine drug screening), and a resting 12-lead Electrocardiogram with a 10 second rhythm strip.
- Adequate peripheral venous access for IV insertion and blood sample collection (assessments will be made prior to undergoing further assessments).
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- HAPE-susceptible individuals (Study 2 only) must have had a medically documented (hospital admission or emergency room visit) HAPE episode characterized by noncardiogenic pulmonary edema and hypoxemia that occurred during high altitude travel in Colorado and must reside below 3,000 feet (unacclimatized individuals; non-Colorado residents).
- HAPE-resistant individuals (Study 2 only) will have had no evidence of HAPE during high altitude travel in Colorado, and must reside below 3,000 feet (unacclimatized; often being travel partners of HAPE-susceptible subjects).
- Healthy controls (Study 1 only) will all be Colorado residents.
Who cannot join
- Currently participating in or has been enrolled in another clinical trial within the last 30 days (observational studies are acceptable).
- Donation of any blood or plasma in the last month, or donation of > 500 milliliters (ml) of blood within the 3 months preceding study drug administration.
- Female subjects of childbearing potential with positive serum pregnancy (beta human chorionic gonadotropin) test, who are breastfeeding, plan to become pregnant during the study, or decline to either be abstinent or use highly effective birth control if they have sexual intercourse with a male partner (ie, oral contraceptives; contraceptive patches, implants, injections, and rings; intrauterine devices - both hormonally-impregnated and untreated devices) throughout the study and for at least 1 month after study completion;
- Known history of impaired liver function
- Clinically significant laboratory abnormalities (one retest is allowed at the discretion of the Investigator and Medical Monitor), defined as:
- Impaired renal function as estimated glomerular filtration rate < 60 mL/min/1.73 m2) as estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation at screening.(81)
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- Serum Potassium < 3.2 millimolar (mM)
- aspartate aminotransferase (AST) or alanine transaminase (ALT) > 2x upper reference limit
- international normalized ratio (INR) > 1.5
- Fasting serum triglycerides > 500 mg/dL (lipemic serum affects assays)
- TSH < 0.5 or > 5 milliunits/Liter (mU/L)
- Hemoglobin < 12.0 g/dL
- Bilirubin > 2, unless consistent with Gilbert's disorder (indirect bilirubinemia)
- Platelet count < 100,000/µL
- Any other abnormality deemed by the Investigator to exceed normal safety limits for this study or exclude subject participation.
- Cardiovascular conditions:
- Clinically significant abnormal electrocardiogram at screening:
- Clinically significant abnormal ECG results including but not limited to complete left or right bundle branch block; other ventricular conduction block (except for incomplete bundle branch blocks, with a Q to R to S (QRS) duration < 0.12 sec) ; 2nd degree or 3rd degree atrioventricular (AV) block; sustained ventricular arrhythmia; sustained atrial arrhythmia; two or more premature ventricular contractions (PVC) in a row; pattern of (S wave to T wave) ST segment elevation felt consistent with cardiac ischemia; or any condition deemed clinically significant by a study investigator
- Any history of congenital or acquired long QT syndrome
- Any history of uncorrected re-entrant supraventricular tachycardia, atrial fibrillation, sinus tachycardia (> 100 bpm at rest), or ventricular tachycardia.
- Evidence of conduction abnormality including QTc prolongation on ECG, defined as > 450 msec for men and > 470 msec for women
- Unstable angina pectoris, history of myocardial infarction (MI), transient ischemic attack (TIA) or stroke within 3 months prior to screening, or subjects who have ever undergone percutaneous coronary intervention or a coronary artery bypass or who are due to undergo these procedures at the time of screening, as evidence of atherosclerotic cardiovascular disease (ASCVD).
- New York Heart Association Functional Class I-IV congestive heart failure (any congestive heart failure)
- Use of any blood thinner (e.g. novel oral anticoagulant, coumadin/warfarin). Use of aspirin is acceptable for study and will not need to be discontinued prior to involvement in the study. Use of a P2Y12 inhibitor (such as clopidogrel) is also not permitted due to bleeding risks.
- Use of any phosphodiesterase-5 inhibitors (as prescribed medications or obtained by other means) such as sildenafil, tadalafil, or vardenafil (as they may enhance hypoxic exercise performance)
- Infectious conditions:
- o Active Coronavirus Disease 2019 (COVID-19) or any viral upper respiratory infection suspected by symptoms and/or confirmed by nasal swab polymerase chain reaction (PCR) or rapid antigen within the past 30 days. Subjects will be screened for COVID-19 at study entry by nasal swab antigen test on day 0 regardless of symptoms. A subject with recent COVID-19 will be allowed to participate provided that the diagnosis was made more than 30 days previously, COVID-related symptoms have been absent for 20 or more days, and an antigen test on day 0 is negative.
- Concomitant Medications:
- Nonselective beta-blockers including propranolol, carvedilol, and labetalol (due to antagonization of beta-2 agonist effects)
- Use of any inhaled or oral beta-2 receptor agonists, or oral theophylline
- Non-potassium sparing diuretics (due to hypokalemia risks)
- The use of any medication known to be a strong inhibitor or strong inducer of cytochrome P (CYP) 3A4 or 3A5 enzymes (cytochrome P450 isoenzymes) that metabolize salmeterol.(66) Also, any medication that has been reported to have a major or moderate interaction with salmeterol or fluticasone(82)
- Use of monoamine oxidase inhibitors or tricyclic antidepressants within 2 weeks of screening
- Prescription amphetamines or other sympathetic stimulants used for disorders such as narcolepsy, somnolence, or attention deficit disorder
- History of claustrophobia or post traumatic stress disorder that would limit use of gas breathing masks or mouthpieces.
- Essential tremor limiting handwriting, or any tremor requiring medication.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Colorado Anschutz Medical Campus
Aurora, Colorado, 80045
james maloney, MD, 303-724-6072, james.maloney@cuanschutz.edu
Saedie Hawbaker, MPH, 3037246072, saedie.hawbaker@cuanschutz.edu
About this study
Official title: Double-Blinded, Placebo-Controlled, Randomized, 2 Period, Crossover Phase 1/2a Study Testing Safety/Efficacy of Advair HFA (Salmeterol, Fluticasone) in Resting & Exercising Healthy & High Altitude Pulmonary Edema (HAPE) Predisposed Subjects
The current protocol is composed of two studies. The first study is designed to carefully evaluate the safety of high-dose salmeterol/fluticasone (Advair HFA) versus placebo (hydrofluoroalkane, HFA) administration over 7 days, as well as the efficacy of the study drug to increase exercise performance, in healthy individuals exercising under hypoxic, simulated high-altitude conditions (Phase 1/2a study). The second study will examine sensitive measures of cardiopulmonary function using invasive cardiopulmonary testing, in both HAPE-sensitive and HAPE-resistant individuals, to assess the potential efficacy of salmeterol/fluticasone to prevent pulmonary edema and to enhance exercise capacity (Phase 2a) in these individuals.
Read the detailed description
Both Study 1 and Study 2 are double-blinded, randomized, placebo-controlled, two-period, crossover studies.
Study 1 (Phase 1/2a) is a Double-Blinded, Placebo-Controlled, Randomized, 2 Period, Crossover study examining safety and efficacy in healthy subjects dosed with salmeterol/fluticasone 126mcg/270mcg twice daily vs. placebo, for 7 days. Subjects will exercise under hypoxic conditions one time during each study period with the primary efficacy outcome being maximal oxygen uptake (VO2max), and secondary outcomes of arterial partial pressure of oxygen (PaO2), alveolar-arterial oxygen (Aa) gradient, and blood lactate levels. Continuous cardiac monitoring will occur during study drug dosing and for 5 days after drug discontinuation. ECGs and safety lab tests will be assessed at key intervals during drug dosing. A pause in enrollment will occur for a planned data and safety monitoring board (DSMB) safety analysis after four subjects have completed Study 1. There will also be a full review of safety data once Study 1 is complete prior to initiating Study 2.
Study 2 (Phase 2a) is a Double-Blinded, Placebo-Controlled, Randomized, 2 Period, Crossover study examining efficacy and safety in both healthy (HAPE-resistant) and HAPE-susceptible subjects dosed with salmeterol/fluticasone 126mcg/270mcg twice daily. Subjects will take study drug for two days prior to hypoxic exercise testing in each period of this study, then discontinue study drug when the exercise is completed. Efficacy assessments will include VO2 max (primary outcome), right heart catheter measurements, PaO2, A-a gradients, and blood lactate.
For both studies, investigators and subjects will be blinded to assignment group (order of study drug vs. placebo).
- Conditions
- Altitude Edema
- Being tested
- Advair HFA, Placebo
- Keywords
- salmeterol, fluticasone, exercise performance, high altitude pulmonary edema, hypoxia
- Medical subject headings
- Altitude Sickness, Hypoxia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Advair HFADrug
Also called salmeterol and fluticasone in hydrofluoroalkane (HFA) propellant
6 puffs (total: salmeterol 126 ug and fluticasone 270 ug) twice daily
PlaceboDrug
Also called HFA134a (hydrofluoroalkane 134a, same propellant as in Advair HFA)
HFA134a inhaler
| Study group | Role | What they receive |
|---|---|---|
| Advair HFA (salmeterol 126 ug/fluticasone 270 ug) twice daily for up to 7 days | Experimental | Participants will inhale salmeterol 126 ug and fluticasone 270 ug twice daily for up to 7 days Receives: Drug: Advair HFA |
| Placebo | Placebo comparator | Participants will inhale placebo (same puff number) twice daily for up to 7 days Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
VO2 max
peak oxygen consumption with exercise
Measured: day 3 of treatment
Secondary outcomes (6)
Aa Gradient
alveolar-arterial oxygen Gradient during peak hypoxic exercise
Measured: day 3 of treatment
blood lactate
peak arterial blood lactate during peak hypoxic exercise
Measured: day 3 of treatment
nadir PaO2
lowest arterial partial pressure of oxygen during peak hypoxic exercise
Measured: day 3 of treatment
highest PaO2
highest arterial partial pressure of oxygen during peak hypoxic exercise
Measured: day 3 of treatment
MPAP
highest mean pulmonary arterial pressure (MPAP) during hypoxic exercise
Measured: day 3 of treatment
cardiac output
highest cardiac output during hypoxic exercise
Measured: day 3 of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2023
- Study start12 Dec 2023
- Primary completion1 Dec 2026 (estimated)
- Study completion15 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Altitude EdemaStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- United States Department of Defense
- Responsible party
- Sponsor
- Investigators
- James P Maloney, MD, Principal investigator, Univ. of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06040268
- Sponsor's protocol ID
- 23-0463
- Other IDs
- W81WXH2290024
- Acronym
- SWIFTARC
- Status last verified
- Sep 2025
- First submitted
- 8 Sep 2023
- Last updated
- 22 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Double-Blinded, Placebo-Controlled, Randomized, 2 Period, Crossover Phase 1/2a Study Testing Safety/Efficacy of Advair HFA (Salmeterol, Fluticasone) in Resting & Exercising Healthy & High Altitude Pulmonary Edema (HAPE) Predisposed Subjects
- ClinicalTrials.gov ID
- NCT06040268
- Acronym / sponsor ID
- SWIFTARC / 23-0463
- Conditions
- Altitude Edema
- Keywords
- salmeterol, fluticasone, exercise performance, high altitude pulmonary edema, hypoxia
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- United States Department of Defense
- Study start
- 12 Dec 2023 (actual)
- Primary completion
- 1 Dec 2026 (estimated)
- Study completion
- 15 Dec 2026 (estimated)
- First posted
- 15 Sep 2023 (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 current protocol is composed of two studies. The first study is designed to carefully evaluate the safety of high-dose salmeterol/fluticasone (Advair HFA) versus placebo (hydrofluoroalkane, HFA) administration over 7 days, as well as the efficacy of the study drug to increase exercise performance, in healthy individuals exercising under hypoxic, simulated high-altitude conditions (Phase 1/2a study). The second study will examine sensitive measures of cardiopulmonary function using invasive cardiopulmonary testing, in both HAPE-sensitive and HAPE-resistant individuals, to assess the potential efficacy of salmeterol/fluticasone to prevent pulmonary edema and to enhance exercise capacity (Phase 2a) in these individuals.
Detailed description
Both Study 1 and Study 2 are double-blinded, randomized, placebo-controlled, two-period, crossover studies.
Study 1 (Phase 1/2a) is a Double-Blinded, Placebo-Controlled, Randomized, 2 Period, Crossover study examining safety and efficacy in healthy subjects dosed with salmeterol/fluticasone 126mcg/270mcg twice daily vs. placebo, for 7 days. Subjects will exercise under hypoxic conditions one time during each study period with the primary efficacy outcome being maximal oxygen uptake (VO2max), and secondary outcomes of arterial partial pressure of oxygen (PaO2), alveolar-arterial oxygen (Aa) gradient, and blood lactate levels. Continuous cardiac monitoring will occur during study drug dosing and for 5 days after drug discontinuation. ECGs and safety lab tests will be assessed at key intervals during drug dosing. A pause in enrollment will occur for a planned data and safety monitoring board (DSMB) safety analysis after four subjects have completed Study 1. There will also be a full review of safety data once Study 1 is complete prior to initiating Study 2.
Study 2 (Phase 2a) is a Double-Blinded, Placebo-Controlled, Randomized, 2 Period, Crossover study examining efficacy and safety in both healthy (HAPE-resistant) and HAPE-susceptible subjects dosed with salmeterol/fluticasone 126mcg/270mcg twice daily. Subjects will take study drug for two days prior to hypoxic exercise testing in each period of this study, then discontinue study drug when the exercise is completed. Efficacy assessments will include VO2 max (primary outcome), right heart catheter measurements, PaO2, A-a gradients, and blood lactate.
For both studies, investigators and subjects will be blinded to assignment group (order of study drug vs. placebo).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Advair HFA (salmeterol 126 ug/fluticasone 270 ug) twice daily for up to 7 days | Experimental | Drug: Advair HFAParticipants will inhale salmeterol 126 ug and fluticasone 270 ug twice daily for up to 7 days |
| Placebo | Placebo comparator | Drug: PlaceboParticipants will inhale placebo (same puff number) twice daily for up to 7 days |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Written informed consent signed prior to entry into the study.
- Male or female age 18-50 years of age
- BMI ≥ 20 and < 35 kg/m2
- Agreement to comply with the study-required interventions and treatment during the full duration of the study.
- In good health as determined by screening medical history, physical examination, vital signs (blood pressure, heart rate, respiratory rate and temperature), clinical laboratory tests (CBC, protime (PT) (INR)/partial thromboplastin time (PTT), thyroid stimulating hormone (TSH), Total Bilirubin, blood chemistries, urine drug screening), and a resting 12-lead Electrocardiogram with a 10 second rhythm strip.
Key exclusion criteria (36 listed)
- Currently participating in or has been enrolled in another clinical trial within the last 30 days (observational studies are acceptable).
- Donation of any blood or plasma in the last month, or donation of > 500 milliliters (ml) of blood within the 3 months preceding study drug administration.
- Female subjects of childbearing potential with positive serum pregnancy (beta human chorionic gonadotropin) test, who are breastfeeding, plan to become pregnant during the study, or decline to either be abstinent or use highly effective birth control if they have sexual intercourse with a male partner (ie, oral contraceptives; contraceptive patches, implants, injections, and rings; intrauterine devices - both hormonally-impregnated and untreated devices) throughout the study and for at least 1 month after study completion;
- Known history of impaired liver function
- Clinically significant laboratory abnormalities (one retest is allowed at the discretion of the Investigator and Medical Monitor), defined as:
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 |
|---|---|---|
| Advair HFAAlso: salmeterol and fluticasone in hydrofluoroalkane (HFA) propellant6 puffs (total: salmeterol 126 ug and fluticasone 270 ug) twice daily | Drug | Advair HFA (salmeterol 126 ug/fluticasone 270 ug) twice daily for up to 7 days |
| PlaceboAlso: HFA134a (hydrofluoroalkane 134a, same propellant as in Advair HFA)HFA134a inhaler | Drug | Placebo |
Primary outcome
VO2 max
Time frame: day 3 of treatment
peak oxygen consumption with exercise
6 secondary outcomes
Aa Gradient
Time frame: day 3 of treatment
blood lactate
Time frame: day 3 of treatment
nadir PaO2
Time frame: day 3 of treatment
highest PaO2
Time frame: day 3 of treatment
MPAP
Time frame: day 3 of treatment
cardiac output
Time frame: day 3 of treatment
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 22 Sep 2025.
- Individual participant dataSharing planned: No
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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.
James P Maloney, MD principal investigator
Univ. of Colorado, Denver
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Advair HFA in people with Altitude Edema, run by University of Colorado, Denver at 1 site in United States.
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 9 inclusion and 36 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: looking for participants now, as of the sponsor's last update on 22 Sep 2025. 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 United States. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 James P Maloney, MD (3037246072, james.maloney@ucdenver.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
VO2 max (time frame: day 3 of treatment). 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 22 Sep 2025; AzTrials last refreshed its copy on 26 Oct 2026.