Best African American Response to Asthma Drugs

Study Overview
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Brief Summary
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The purpose of this study is to find the best asthma treatment to add for Blacks who have asthma that is not well controlled on a low dose of inhaled steroid. This study will also try to find out if Black adults and children differ in how they respond to the medications used in this study.

Detailed Description
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BARD is a 66 week prospective, randomized, double-blind, crossover trial in Blacks (individuals who self-report Black ancestry) who have inadequately controlled asthma while taking low-dose inhaled corticosteroids (ICS). BARD will examine the efficacy of increasing the dose of ICS with or without the addition of a long-acting beta agonist (LABA) to determine whether individual patients respond better to one treatment than another and, if so, whether the responses are different for children and adults or if they are related to genetic ancestry.

Official Title
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Best African American Response to Asthma Drugs

Conditions
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Asthma

Intervention / Treatment
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* Drug: Flovent Diskus® 100 mcg
* Drug: Flovent Diskus® 250 mcg
* Drug: Flovent Diskus® 500 mcg
* Drug: Advair Diskus® 100/50 mcg
* Drug: Advair Diskus® 250/50 mcg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals who self-report Black ancestry (with at least 1 Black grandparent). Able to perform reproducible spirometry according to ATS criteria. Clinical history consistent with asthma. Baseline FEV1≥40% of predicted and/or post-bronchodilator FEV1≥40% of predicted. Asthma confirmed either by: (1) Beta-agonist reversibility to 4 puffs albuterol ≥ 12% OR (2) PC20FEV1 ≤ 16 mg/ml OR (3) an absolute relative change in %predicted FEV1 of ≥ 12% over two measurements documented by repeat spirogram over the previous year Either: A) inadequately controlled on low-, medium- or high-dose ICS monotherapy, or low- or medium-dose ICS/LABA, or B) well-controlled on medium- or high-dose ICS monotherapy, or low-, medium- or high-dose ICS/LABA. Inadequate asthma control will be defined as an ACT/c-ACT score <20; well-controlled asthma will be defined as an ACT/c-ACT score ≥20. Stable asthma controller therapy dose (ICS or ICS/LABA) for the 2 weeks prior to enrollment. Non-smoker (total lifetime smoking history < 5 pack-years if <18, or <10 pack-years if ≥18 years of age; no smoking for at least 1 year). For participants ≥18 years of age: Ability to provide informed consent. For participants under 18 years of age: Ability to provide verbal or written assent and ability of parent to provide informed consent. Exclusion Criteria: Medical contraindication to LABA or history of adverse reactions to ICS or LABA preparations or any of their ingredients. Current or prior use of medications known to significantly interact with corticosteroid disposition within the two-week period preceding enrollment. Unwilling to provide a blood sample for DNA extraction and genetic analysis. Major medical problems prohibiting study participation, i.e. presence of chronic or active lung disease other than asthma or history of unstable significant medical illness other than asthma, including thyroid disease, diabetes mellitus, Cushing's disease, Addison's disease, hepatic disease, or concurrent medical problems that could require oral corticosteroids during the study or that would place the participant at increased risk. Systemic corticosteroid treatment for any condition within 4 weeks of enrollment or more than five courses of systemic corticosteroids in the past year. History of a life-threatening asthma exacerbation requiring intubation, mechanical ventilation, or resulting in a hypoxic seizure within the last 2 years. History of a respiratory tract infection within 4 weeks of enrollment. If a female of child-bearing potential, failure to practice abstinence or use an acceptable birth control method. Pregnancy or lactation or planning to get pregnant during the course of the trial. Receiving hyposensitization therapy other than an established maintenance regimen defined as a continuous regimen for ≥ 3 months prior to enrollment. Participation in an intervention trial or use of investigative drugs in the past 30 days or plans to enroll in such a trial during the study.

Ages Eligible for Study
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Minimum Age: 5 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Crossover sequence 1<br>Flovent Diskus® 250 mcg,followed by Advair Diskus® 250/50 mcg, followed by Flovent Diskus® 100 mcg, followed by Advair Diskus® 100/50 mcg | Drug: Flovent Diskus® 100 mcg<br>* Flovent is an ICS<br>Drug: Flovent Diskus® 250 mcg<br>* Flovent is an ICS<br>Drug: Advair Diskus® 100/50 mcg<br>* Advair is an ICS/LABA combination<br>Drug: Advair Diskus® 250/50 mcg<br>* Advair is an ICS/LABA combination<br>|
| Experimental: Crossover sequence 2<br>Advair Diskus® 250/50 mcg, followed by Advair Diskus® 100/50 mcg, followed by Flovent Diskus® 250 mcg, followed by Flovent Diskus® 100 mcg | Drug: Flovent Diskus® 100 mcg<br>* Flovent is an ICS<br>Drug: Flovent Diskus® 250 mcg<br>* Flovent is an ICS<br>Drug: Advair Diskus® 100/50 mcg<br>* Advair is an ICS/LABA combination<br>Drug: Advair Diskus® 250/50 mcg<br>* Advair is an ICS/LABA combination<br>|
| Experimental: Crossover sequence 3<br>Flovent Diskus® 100 mcg, followed by Flovent Diskus® 250 mcg, followed by Advair Diskus® 100/50 mcg, followed by Advair Diskus® 250/50 mcg | Drug: Flovent Diskus® 100 mcg<br>* Flovent is an ICS<br>Drug: Flovent Diskus® 250 mcg<br>* Flovent is an ICS<br>Drug: Advair Diskus® 100/50 mcg<br>* Advair is an ICS/LABA combination<br>Drug: Advair Diskus® 250/50 mcg<br>* Advair is an ICS/LABA combination<br>|
| Experimental: Crossover sequence 4<br>Advair Diskus® 100/50 mcg, followed by Flovent Diskus® 100 mcg, followed by Advair Diskus® 250/50 mcg, followed by Flovent Diskus® 250 mcg | Drug: Flovent Diskus® 100 mcg<br>* Flovent is an ICS<br>Drug: Flovent Diskus® 250 mcg<br>* Flovent is an ICS<br>Drug: Advair Diskus® 100/50 mcg<br>* Advair is an ICS/LABA combination<br>Drug: Advair Diskus® 250/50 mcg<br>* Advair is an ICS/LABA combination<br>|
| Experimental: Crossover sequence 5<br>Flovent Diskus® 500 mcg, followed by Advair Diskus® 250/50 mcg, followed by Flovent Diskus® 250 mcg, followed by Advair Diskus® 100/50 mcg | Drug: Flovent Diskus® 250 mcg<br>* Flovent is an ICS<br>Drug: Flovent Diskus® 500 mcg<br>* Flovent is an ICS<br>Drug: Advair Diskus® 100/50 mcg<br>* Advair is an ICS/LABA combination<br>Drug: Advair Diskus® 250/50 mcg<br>* Advair is an ICS/LABA combination<br>|
| Experimental: Crossover sequence 6<br>Advair Diskus® 250/50 mcg, followed by Advair Diskus® 100/50 mcg, followed by Flovent Diskus® 500 mcg, followed by Flovent Diskus® 250 mcg | Drug: Flovent Diskus® 250 mcg<br>* Flovent is an ICS<br>Drug: Flovent Diskus® 500 mcg<br>* Flovent is an ICS<br>Drug: Advair Diskus® 100/50 mcg<br>* Advair is an ICS/LABA combination<br>Drug: Advair Diskus® 250/50 mcg<br>* Advair is an ICS/LABA combination<br>|
| Experimental: Crossover sequence 7<br>Flovent Diskus® 250 mcg, followed by Flovent Diskus® 500 mcg, followed by Advair Diskus® 100/50 mcg, followed by Advair Diskus® 250/50 mcg | Drug: Flovent Diskus® 250 mcg<br>* Flovent is an ICS<br>Drug: Flovent Diskus® 500 mcg<br>* Flovent is an ICS<br>Drug: Advair Diskus® 100/50 mcg<br>* Advair is an ICS/LABA combination<br>Drug: Advair Diskus® 250/50 mcg<br>* Advair is an ICS/LABA combination<br>|
| Experimental: Crossover sequence 8<br>Advair Diskus® 100/50 mcg, followed by Flovent Diskus® 250 mcg, followed by Advair Diskus® 250/50 mcg, followed by Flovent Diskus® 500 mcg | Drug: Flovent Diskus® 250 mcg<br>* Flovent is an ICS<br>Drug: Flovent Diskus® 500 mcg<br>* Flovent is an ICS<br>Drug: Advair Diskus® 100/50 mcg<br>* Advair is an ICS/LABA combination<br>Drug: Advair Diskus® 250/50 mcg<br>* Advair is an ICS/LABA combination<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Primary Outcome is a Composite Measure That Uses Exacerbations, Asthma Control Days During the Last 12 of 14 Weeks of a Treatment Regimen, and Percent Predicted FEV1 at the End of a Treatment Regimen. | This composite outcome uses a hierarchical method to ascertain differences in asthma control. For each participant, treatments are first compared to see if they differ in terms of exacerbations. If one treatment results in fewer exacerbations than another, it is deemed the superior treatment and no further comparisons are made. If treatment superiority cannot be assigned by exacerbations, then they are compared by asthma control days (ACDs). If one treatment yields at least 31 annualized ACDs more than another, it is deemed the superior treatment. If treatment superiority still cannot be assigned by ACDs, then they are compared by percent predicted FEV1 at the end of a treatment period. If one treatment yields at least 5% greater FEV1 than another, it is deemed the superior treatment. If treatment superiority cannot be assigned by exacerbations, ACDs or FEV1, then that participant is classified as having no differential response. | The last 12 weeks of each 14-week treatment period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fluticasone, Asthma, Salmeterol