Best African American Response to Asthma Drugs (BARD)

Penn State Health

Status and phase: Completed; Phase 3

Conditions: Asthma

Treatments: Drug: Flovent Diskus® 100 mcg; Drug: Advair Diskus® 250/50 mcg; Drug: Flovent Diskus® 250 mcg; Drug: Flovent Diskus® 500 mcg; Drug: Advair Diskus® 100/50 mcg

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01967173

AsthmaNet 006

1U10HL098115 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 574 patients

Sex: All

Ages: 5+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Individuals who self-report Black ancestry (with at least 1 Black grandparent).
2. Able to perform reproducible spirometry according to ATS criteria.
3. Clinical history consistent with asthma.
4. Baseline FEV1≥40% of predicted and/or post-bronchodilator FEV1≥40% of predicted.
5. 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
6. 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.
7. Stable asthma controller therapy dose (ICS or ICS/LABA) for the 2 weeks prior to enrollment.
8. 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).
9. 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

1. Medical contraindication to LABA or history of adverse reactions to ICS or LABA preparations or any of their ingredients.
2. Current or prior use of medications known to significantly interact with corticosteroid disposition within the two-week period preceding enrollment.
3. Unwilling to provide a blood sample for DNA extraction and genetic analysis.
4. 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.
5. Systemic corticosteroid treatment for any condition within 4 weeks of enrollment or more than five courses of systemic corticosteroids in the past year.
6. History of a life-threatening asthma exacerbation requiring intubation, mechanical ventilation, or resulting in a hypoxic seizure within the last 2 years.
7. History of a respiratory tract infection within 4 weeks of enrollment.
8. If a female of child-bearing potential, failure to practice abstinence or use an acceptable birth control method.
9. Pregnancy or lactation or planning to get pregnant during the course of the trial.
10. Receiving hyposensitization therapy other than an established maintenance regimen defined as a continuous regimen for ≥ 3 months prior to enrollment.
11. 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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574 participants in 8 patient groups

Crossover sequence 1

Experimental group

Description:

Flovent Diskus® 250 mcg,followed by Advair Diskus® 250/50 mcg, followed by Flovent Diskus® 100 mcg, followed by Advair Diskus® 100/50 mcg

Treatment:

Drug: Flovent Diskus® 100 mcg

Drug: Flovent Diskus® 250 mcg

Drug: Advair Diskus® 100/50 mcg

Drug: Advair Diskus® 250/50 mcg

Crossover sequence 2

Experimental group

Description:

Advair Diskus® 250/50 mcg, followed by Advair Diskus® 100/50 mcg, followed by Flovent Diskus® 250 mcg, followed by Flovent Diskus® 100 mcg

Treatment:

Drug: Flovent Diskus® 100 mcg

Drug: Flovent Diskus® 250 mcg

Drug: Advair Diskus® 100/50 mcg

Drug: Advair Diskus® 250/50 mcg

Crossover sequence 3

Experimental group

Description:

Flovent Diskus® 100 mcg, followed by Flovent Diskus® 250 mcg, followed by Advair Diskus® 100/50 mcg, followed by Advair Diskus® 250/50 mcg

Treatment:

Drug: Flovent Diskus® 100 mcg

Drug: Flovent Diskus® 250 mcg

Drug: Advair Diskus® 100/50 mcg

Drug: Advair Diskus® 250/50 mcg

Crossover sequence 4

Experimental group

Description:

Advair Diskus® 100/50 mcg, followed by Flovent Diskus® 100 mcg, followed by Advair Diskus® 250/50 mcg, followed by Flovent Diskus® 250 mcg

Treatment:

Drug: Flovent Diskus® 100 mcg

Drug: Flovent Diskus® 250 mcg

Drug: Advair Diskus® 100/50 mcg

Drug: Advair Diskus® 250/50 mcg

Crossover sequence 5

Experimental group

Description:

Flovent Diskus® 500 mcg, followed by Advair Diskus® 250/50 mcg, followed by Flovent Diskus® 250 mcg, followed by Advair Diskus® 100/50 mcg

Treatment:

Drug: Flovent Diskus® 250 mcg

Drug: Flovent Diskus® 500 mcg

Drug: Advair Diskus® 100/50 mcg

Drug: Advair Diskus® 250/50 mcg

Crossover sequence 6

Experimental group

Description:

Advair Diskus® 250/50 mcg, followed by Advair Diskus® 100/50 mcg, followed by Flovent Diskus® 500 mcg, followed by Flovent Diskus® 250 mcg

Treatment:

Drug: Flovent Diskus® 250 mcg

Drug: Flovent Diskus® 500 mcg

Drug: Advair Diskus® 100/50 mcg

Drug: Advair Diskus® 250/50 mcg

Crossover sequence 7

Experimental group

Description:

Flovent Diskus® 250 mcg, followed by Flovent Diskus® 500 mcg, followed by Advair Diskus® 100/50 mcg, followed by Advair Diskus® 250/50 mcg

Treatment:

Drug: Flovent Diskus® 250 mcg

Drug: Flovent Diskus® 500 mcg

Drug: Advair Diskus® 100/50 mcg

Drug: Advair Diskus® 250/50 mcg

Crossover sequence 8

Experimental group

Description:

Advair Diskus® 100/50 mcg, followed by Flovent Diskus® 250 mcg, followed by Advair Diskus® 250/50 mcg, followed by Flovent Diskus® 500 mcg

Treatment:

Drug: Flovent Diskus® 250 mcg

Drug: Flovent Diskus® 500 mcg

Drug: Advair Diskus® 100/50 mcg

Drug: Advair Diskus® 250/50 mcg