AsthmaNet Best African American Response to Asthma Drugs (BARD)

HLB02152020a

AsthmaNet-BARD

False

Asthma

Bronchial Diseases

Respiratory Tract Diseases

Lung Diseases, Obstructive

Lung Diseases

Respiratory Hypersensitivity

Hypersensitivity, Immediate

Hypersensitivity

Immune System Diseases

Fluticasone

Xhance

Fluticasone-Salmeterol Drug Combination

Bronchodilator Agents

Autonomic Agents

Peripheral Nervous System Agents

Physiological Effects of Drugs

Anti-Asthmatic Agents

Respiratory System Agents

Glucocorticoids

Hormones

Hormones, Hormone Substitutes, and Hormone Antagonists

Sympathomimetics

Anti-Inflammatory Agents

Dermatologic Agents

Anti-Allergic Agents

Released

True

True

Coded

False

Clinical Trial

Open BioLINCC Study

Both

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

2020-01-27

2022-06-24

2020-01-27

None

February 2014 – July 2017

DLD

Lung

non-HIV

non-COVID

None

None

No

No

No

No

Yes, For Some Specimens

No

Some subjects allow use of their specimens for genetic use

Asthma

To assess whether patients of African American heritage with inadequately controlled asthma benefit from the addition of a long-acting beta-agonist and/or increased glucocorticoids dosage, and whether the response varies for children vs. adolescents and adults.

Epidemiologic studies have demonstrated that African American patients with asthma experience more complications including exacerbations, asthma-related urgent-care visits, hospitalizations, and deaths, as compared to Caucasian patients with asthma. Ethnicity can also influence medication response, and studies have shown that African Americans patients have more glucocorticoid resistance, less cellular sensitivity to glucocorticoids, and more eosinophilic inflammation during inhaled glucocorticoid treatment than Caucasian patients. This may be due to the effect of genetic variants on response to pharmacotherapy for asthma.

Asthma symptoms are primarily controlled with inhaled glucocorticoids, but a longacting β2-adrenergic receptor agonist (LABA) may be used as an additional treatment when glucocorticoids alone do not sufficiently suppress symptoms. However, prior to the BARD study, this recommendation was based on studies with limited numbers of African American patients and without evaluation of differences in genetic ancestry. In particular, additional analysis has indicated that adding a LABA was not superior to increasing the dose of an inhaled glucocorticoid in African American patients. Therefore, the BARD trials were initiated to address this gap in scientific understanding and determine a preferred pharmacotherapy strategy in African American children, adolescents, and adults.

Eligible participants were recruited from nine AsthmaNet sites and consisted of asthma patients at least five years of age that had at least one African American grandparent. Participants were required to have a baseline forced expiratory volume in 1 second (FEV1) of at least 40% of the predicted value after bronchodilator use (four 90 μg puffs of albuterol) and a diagnosis of asthma, as confirmed by beta-agonist reversibility, a methacholine provocation concentration causing a 20% decrease in the FEV1 of 16 mg per milliliter or less, or an absolute difference in the percentage of the predicted FEV1 of at least 12 percentage points over two measurements documented within the previous year. The asthma must also be inadequately controlled (CT/c-ACT score <20) while on a low-dose inhaled glucocorticoid.

A total of 280 children and 294 adolescents and adults were enrolled and underwent randomization.

BARD consisted of two prospective, randomized, double-blind trials. One trial involved children 5 to 11 years of age with four treatment groups: doubling the dose of an inhaled glucocorticoid (fluticasone propionate) to 100 μg twice daily; doubling the dose of fluticasone to 100 μg and adding a LABA (salmeterol) at a dose of 50 μg; quintupling the dose of fluticasone to 250 μg; or quintupling the dose of fluticasone to 250 μg and adding 50 μg of salmeterol. The other trial involved adolescents and adults 12 years of age or older with four treatment groups: adding twice-daily salmeterol at a dose of 50 μg to baseline twice-daily administration of fluticasone propionate at a dose of 100 μg; increasing the dose of fluticasone by a factor of 2.5 to 250 μg; quintupling the dose of fluticasone to 500 μg; or increasing the dose of fluticasone by a factor of 2.5 to 250 μg and adding 50 μg of salmeterol. The first step-up regimen differed between trials due to the lack of a low-dose inhaled glucocorticoid–LABA medication for children. The trials were otherwise identical in design and step-up dosing strategies.

The run-in period consisted of treatment up to 10 weeks with an open-label low-dose inhaled glucocorticoid (50 μg of fluticasone propionate twice daily in children and 100 μg twice daily in adolescents and adults) in order to assess whether patients had inadequately controlled asthma prior to randomization. Eligible patients were then randomly assigned to the step-up treatment sequences, each lasting 14 weeks, in a four-way crossover design with add-on LABA, different strengths of increased doses of inhaled glucocorticoid, or an increased dose of inhaled glucocorticoid with LABA in dry-powder. The initial 2 weeks of each period were considered to be a washout period for the previous treatment and a wash-in period for the new regimen.

The primary clinical outcome of each trial was a hierarchical composite measure that sequentially evaluated asthma exacerbations, asthma-control days, and lung function (percentage of the predicted FEV1) at the end of the 14-week treatment regimens to determine a differential response.

In African American adolescents and adults with poorly controlled asthma, the addition of a LABA to inhaled glucocorticoid was more likely to produce superior responses than increasing the dose of an inhaled glucocorticoid. In contrast, almost half of the African American children with poorly controlled asthma had a superior response to an increase in the dose of an inhaled glucocorticoid and almost half had a superior response to the addition of a LABA.

Wechsler ME, Szefler SJ, Ortega VE, et al. Step-Up Therapy in Black Children and Adults with Poorly Controlled Asthma. N Engl J Med. 2019 Sep 26;381(13):1227-1239. doi: 10.1056/NEJMoa1905560.

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