Clinical trial NCT01967173: Best African American Response to Asthma Drugs
Official title: Best African American Response to Asthma Drugs
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Asthma
Keywords: Asthma
Fluticasone
Salmeterol
Lead sponsor: Milton S. Hershey Medical Center
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2013-10-22
Enrollment: 574
Sex: ALL
Minimum age (years): 5
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: The last 12 weeks of each 14-week treatment period
Secondary outcomes:
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona College of Medicine
state: Arizona
city: Oakland
country: United States
facility: Children's Hospital & Research Center Oakland
state: California
city: San Francisco
country: United States
facility: UCSF Benioff Children's Hospital
state: California
city: San Francisco
country: United States
facility: University of California - San Francisco
state: California
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Jacksonville
country: United States
facility: Nemours Children's Clinic
state: Florida
city: Orlando
country: United States
facility: Nemours Children's Clinic
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Chicago
country: United States
facility: Ann and Robert H. Lurie Children's Hospital
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Boston
country: United States
facility: Brigham & Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
city: Saint Louis
country: United States
facility: St. Louis Children's Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Durham
country: United States
facility: Duke University School of Medicine
state: North Carolina
city: Raleigh
country: United States
facility: North Carolina Clinical Research
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Cleveland
country: United States
facility: Rainbow Babies and Children's Hospital, Case Western Reserve University
state: Ohio
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Madison
country: United States
facility: University of Wisconsin-Madison
state: Wisconsin
city: Milwaukee
country: United States
facility: Center for Urban Population Health
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: William Busse, MD
role: STUDY_CHAIR
References:
citation: Wechsler ME, Szefler SJ, Ortega VE, Pongracic JA, Chinchilli V, Lima JJ, Krishnan JA, Kunselman SJ, Mauger D, Bleecker ER, Bacharier LB, Beigelman A, Benson M, Blake KV, Cabana MD, Cardet JC, Castro M, Chmiel JF, Covar R, Denlinger L, DiMango E, Fitzpatrick AM, Gentile D, Grossman N, Holguin F, Jackson DJ, Kumar H, Kraft M, LaForce CF, Lang J, Lazarus SC, Lemanske RF Jr, Long D, Lugogo N, Martinez F, Meyers DA, Moore WC, Moy J, Naureckas E, Olin JT, Peters SP, Phipatanakul W, Que L, Raissy H, Robison RG, Ross K, Sheehan W, Smith LJ, Solway J, Sorkness CA, Sullivan-Vedder L, Wenzel S, White S, Israel E; NHLBI AsthmaNet. 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.