Advair HFA for Altitude Edema

(SWIFTARC Trial)

Overseen By James P Maloney, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Colorado, Denver

Must not be taking: Blood thinners, PDE-5 inhibitors

Disqualifiers: Impaired liver function, cardiovascular conditions, others

Compensation: Varies

Number of Visits: 2

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the use of Advair HFA, a medication typically used for asthma, to determine if it can prevent altitude sickness, specifically high-altitude pulmonary edema (HAPE). Researchers aim to discover whether the medication can enhance exercise performance and prevent fluid buildup in the lungs at high altitudes. The study consists of two parts: one for healthy individuals simulating high-altitude conditions and another for those who have either experienced HAPE or are resistant to it. Ideal candidates for this trial include healthy individuals living in Colorado or those who have experienced or are resistant to HAPE during high-altitude travel in Colorado. As a Phase 1, Phase 2 trial, this research seeks to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to early-stage medical advancements.

Will I have to stop taking my current medications?

The trial requires participants to stop taking certain medications, including nonselective beta-blockers, inhaled or oral beta-2 receptor agonists, non-potassium sparing diuretics, and medications that strongly interact with the study drug. If you are on any of these, you may need to stop them before joining the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that Advair HFA, which combines salmeterol and fluticasone, is generally safe for use. Studies indicate its safety is comparable to another medication, Advair Diskus. Most people taking it do not experience serious side effects. No reports of unusual or severe side effects have emerged when used as directed. This information can reassure those considering joining a trial with this treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for altitude edema?

Unlike the standard treatments for altitude edema, which often include medications like acetazolamide or dexamethasone, Advair HFA combines two active ingredients, salmeterol and fluticasone, delivered via an inhaler. This combination offers a unique approach by targeting both inflammation and bronchoconstriction directly in the lungs. Researchers are excited about Advair HFA because it could potentially provide faster relief of symptoms and reduce the reliance on systemic medications, which can have more side effects. Additionally, using an inhaler for delivery means the medication acts quickly and directly where it's needed most.

What evidence suggests that Advair HFA might be an effective treatment for altitude edema?

Research has shown that the ingredients in Advair HFA, fluticasone and salmeterol, effectively improve lung function for people with asthma and COPD, a lung disease that makes breathing difficult. Other studies have found that inhaling salmeterol can reduce the risk of high-altitude pulmonary edema, a condition where fluid builds up in the lungs, by more than 50%. This trial will test Advair HFA, which participants in one arm will inhale, to determine if it can help prevent altitude sickness, especially in those more sensitive to it. The treatment works by opening airways and reducing swelling, making breathing and exercising at high altitudes easier. ^{1 2 6 7 8}

Who Is on the Research Team?

James P Maloney, MD

Principal Investigator

Univ. of Colorado, Denver

Are You a Good Fit for This Trial?

This trial is for healthy individuals aged 18-50, with a BMI between 20 and <35. Participants must be in good health as confirmed by medical exams and tests, agree to follow the study's procedures, and have good veins for IVs. For part of the study, people either need a history of high-altitude pulmonary edema (HAPE) or no HAPE during high altitude exposure.

Inclusion Criteria

You agree to abide by the specified interventions and treatments for the entirety of the study.

In Study 2, you must have no evidence of HAPE when travelling to high altitude locations in Colorado and reside at or below 3,000 feet without acclimatization (e.g., as a travel partner with someone who is susceptible to HAPE).

I am in good health based on recent medical exams and tests.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment (Study 1)

Participants receive salmeterol/fluticasone or placebo for 7 days with exercise under hypoxic conditions and continuous cardiac monitoring

7 days

1 visit (in-person) for exercise testing

Washout

Participants undergo a washout period between crossover periods

7 days

Treatment (Study 2)

Participants receive salmeterol/fluticasone or placebo for 2 days prior to hypoxic exercise testing, with efficacy assessments including VO2 max and right heart catheter measurements

2 days

1 visit (in-person) for exercise testing

Follow-up

Participants are monitored for safety and effectiveness after treatment, including continuous cardiac monitoring and safety lab tests

5 days

What Are the Treatments Tested in This Trial?

Interventions

• Advair HFA
• Placebo

Trial Overview The trial is testing Advair HFA against a placebo over seven days to see if it's safe and can improve exercise performance under simulated high-altitude conditions. It also looks at how well it prevents pulmonary edema and boosts exercise capacity in those prone or resistant to HAPE.

How Is the Trial Designed?

Group I: Advair HFA (salmeterol 126 ug/fluticasone 270 ug) twice daily for up to 7 days Experimental Treatment 1 Intervention

Participants will inhale salmeterol 126 ug and fluticasone 270 ug twice daily for up to 7 days

Group II: Placebo Placebo Group 1 Intervention

Participants will inhale placebo (same puff number) twice daily for up to 7 days

Advair HFA is already approved in United States, European Union for the following indications:

Approved in United States as Advair HFA for:

• Asthma

Approved in European Union as Advair HFA for:

• Asthma
• Chronic Obstructive Pulmonary Disease (COPD)

Approved in United States as Wixela Inhub for:

• Asthma
• Chronic Obstructive Pulmonary Disease (COPD)

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

MTEC

Collaborator

Trials

2

Recruited

110+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Published Research Related to This Trial

A study involving 1127 patients with mild-to-moderate asthma showed that Wixela Inhub (the generic version) and Advair Diskus (the brand name) have equivalent therapeutic effects on lung function, as measured by forced expiratory volume in 1 second (FEV1).

Both Wixela Inhub and Advair Diskus were well tolerated, indicating that Wixela Inhub is a safe and effective alternative for treating asthma and COPD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Bioequivalence of Wixela Inhub and Advair Diskus in Adults With Asthma. Ng, D., Kerwin, EM., White, MV., et al.[2021]

In a study of 100 patients with bronchial asthma, the combination of fluticasone and salmeterol dry powder demonstrated a significantly higher treatment efficacy compared to budesonide powder, with improved lung function and reduced inflammatory factors.

The treatment with fluticasone and salmeterol also had a lower incidence of adverse reactions, indicating a favorable safety profile that supports its use as a promising option for asthma management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Fluticasone and Salmeterol Dry Powder in Treating Patients with Bronchial Asthma and Its Effect on Inflammatory Factors and Pulmonary Function. Zhang, X., Liu, M., Mao, Y.[2023]

In a study of 274 asthmatic patients, adding salmeterol to a low or intermediate dose of fluticasone propionate resulted in significantly better lung function and symptom control compared to simply doubling the fluticasone dose over 12 weeks.

Patients receiving salmeterol experienced greater improvements in peak expiratory flow rates and symptom-free days, with no significant differences in adverse effects between the two treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Addition of salmeterol versus doubling the dose of fluticasone propionate in patients with mild to moderate asthma. van Noord, JA., Schreurs, AJ., Mol, SJ., et al.[2019]

Wixela™ Inhub™ is a generic version of Advair Diskus® and has been shown to have comparable in vitro performance and clinical effectiveness in improving lung function for patients with asthma and COPD.

Bioequivalence studies confirm that Wixela Inhub delivers similar doses of fluticasone propionate and salmeterol as Advair Diskus, making it a viable treatment option for patients whose symptoms are not controlled by inhaled corticosteroids alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Wixela Inhub: A Generic Equivalent Treatment Option for Patients with Asthma or COPD. Donohue, JF., Burgoyne, DS., Ward, JK., et al.[2021]

Wixela Inhub, a generic version of Advair Diskus, demonstrated comparable in vitro performance in delivering medication across various flow rates, confirming its effectiveness for treating asthma and COPD.

In a patient inhalation study involving 68 participants (40 children and 28 adults), Wixela Inhub showed acceptable inhalation profiles, with peak inhaled flow rates that, while slightly lower than those of Advair Diskus, did not affect its bioequivalence or substitutability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Wixela Inhub: Dosing Performance In Vitro and Inhaled Flow Rates in Healthy Subjects and Patients Compared with Advair Diskus. Cooper, A., Parker, J., Berry, M., et al.[2021]

Wixela Inhub demonstrated pharmacokinetic bioequivalence to Advair Diskus for both fluticasone propionate (FP) and salmeterol across all tested doses (100/50, 250/50, and 500/50 μg) in a study involving 66 healthy subjects per dose, confirming its effectiveness as a generic alternative.

Both Wixela Inhub and Advair Diskus were well tolerated, indicating that Wixela Inhub not only matches the efficacy of Advair Diskus but also maintains similar safety profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Equivalent Systemic Exposure to Fluticasone Propionate/Salmeterol Following Single Inhaled Doses from Advair Diskus and Wixela Inhub: Results of Three Pharmacokinetic Bioequivalence Studies. Haughie, S., Allan, R., Wood, N., et al.[2021]

Wixela Inhub, a new generic inhaler combining fluticasone propionate and salmeterol, has been approved as a bioequivalent alternative to Advair Diskus, providing a cost-effective option for asthma and COPD treatment.

Combination therapy with inhaled corticosteroids (ICS) and long-acting beta agonists (LABAs) is recommended for patients with uncontrolled asthma or moderate to severe COPD, highlighting the importance of effective management strategies for these chronic respiratory conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of ICS/LABA Fixed-Dose Combinations in the Treatment of Asthma and COPD: Bioequivalence of a Generic Fluticasone Propionate-Salmeterol Device. Tashkin, DP., Ohar, JA., Koltun, A., et al.[2022]

In a study involving 514 adult patients with persistent asthma, both inhaled triamcinolone acetonide (TAA) formulations (HFA and P-12) showed significant improvements in asthma symptoms and lung function compared to placebo, with effects noticeable as early as 24 hours for peak expiratory flow and 1 week for lung function measurements.

Both TAA formulations demonstrated comparable safety profiles, with no significant differences in adverse events across treatment groups, indicating that both are effective and safe options for asthma management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A controlled trial of chlorofluorocarbon-free triamcinolone acetonide inhalation aerosol in the treatment of adult patients with persistent asthma. Azmacort HFA Study Group. Welch, M., Bernstein, D., Gross, G., et al.[2019]

Wixela Inhub, a dry powder inhaler delivering fluticasone propionate and salmeterol, shows low flow dependency in delivering medication to severe COPD patients, ensuring consistent dosing across varying inhalation profiles.

The study found that both types of breathing simulators used produced similar results for fluticasone propionate, indicating reliability in dose delivery, while slight differences were noted for salmeterol, suggesting the need for further investigation into its delivery characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In Vitro Performance of the Wixela Inhub Inhaler Using Severe Chronic Obstructive Pulmonary Disease Patient Inhalation Profiles. Shepherd, T., Kennett, M., Cooper, A., et al.[2023]

Citations

1. withpower.com withpower.com/trial/phase-2-pulmonary-edema-10-2023-df1f2

Advair HFA for Altitude Edema (SWIFTARC Trial) Research shows that the components of Advair HFA, fluticasone and salmeterol, are effective in improving lung function in conditions like asthma and COPD ( ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06040268

Advair HFA in Healthy and HAPE Predisposed Subjects Subjects will exercise under hypoxic conditions one time during each study period with the primary efficacy outcome being maximal oxygen uptake (VO2max), and ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11706514/

Comparative effectiveness and safety of generic versus ... To compare the effectiveness and safety of Wixela Inhub and Advair Diskus among patients with COPD treated in routine care. Design: A 1:1 ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/12023995/

Salmeterol for the prevention of high-altitude pulmonary ... Prophylactic inhalation of salmeterol decreased the incidence of high-altitude pulmonary edema in susceptible subjects by more than 50 percent.

5. accessdata.fda.gov accessdata.fda.gov/spl/data/f68d433d-1b93-6b17-e053-2995a90adac1/f68d433d-1b93-6b17-e053-2995a90adac1.xml

f68d433d-1b93-6b17-e053-2995a90adac1.xml ... effects of Wixela Inhub ^®? </content> </paragraph> <paragraph> <content styleCode="bold">Wixela Inhub ^® can cause serious side effects ...

6. aging.networkofcare.org aging.networkofcare.org/sanmateo/CommunityResources/ClinicalTrials/Detail/NCT06040268?keyword=%22Altitude%22

Advair HFA in Healthy and 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 ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT00633217

Advair HFA For Chronic Obstructive Pulmonary Disease ... The purpose of this study is to evaluate the efficacy and safety of the FSC HFA MDI in subjects with COPD.

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37549393/

Comparative Effectiveness and Safety of Generic Versus ... Objective: To compare the effectiveness and safety of generic (Wixela Inhub) ... Compared with Advair Diskus use, Wixela Inhub use was associated ...