Best African American Response to Asthma Drugs (BARD)

• ClinicalTrials.gov Identifier: NCT01967173
• Recruitment Status: Completed
• First Posted: October 22, 2013
• Results First Posted: November 15, 2018
• Last Update Posted: November 15, 2018
• Sponsor: Milton S. Hershey Medical Center
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Information provided by (Responsible Party): dave mauger, Milton S. Hershey Medical Center

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Asthma	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	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 574 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Best African American Response to Asthma Drugs
• Study Start Date: February 2014
• Actual Primary Completion Date: July 1, 2017
• Actual Study Completion Date: July 1, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: Crossover sequence 1; 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; Flovent is an ICS; Drug: Flovent Diskus® 250 mcg; Flovent is an ICS; Drug: Advair Diskus® 100/50 mcg; Advair is an ICS/LABA combination; Drug: Advair Diskus® 250/50 mcg; Advair is an ICS/LABA combination
Experimental: Crossover sequence 2; 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; Flovent is an ICS; Drug: Flovent Diskus® 250 mcg; Flovent is an ICS; Drug: Advair Diskus® 100/50 mcg; Advair is an ICS/LABA combination; Drug: Advair Diskus® 250/50 mcg; Advair is an ICS/LABA combination
Experimental: Crossover sequence 3; 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; Flovent is an ICS; Drug: Flovent Diskus® 250 mcg; Flovent is an ICS; Drug: Advair Diskus® 100/50 mcg; Advair is an ICS/LABA combination; Drug: Advair Diskus® 250/50 mcg; Advair is an ICS/LABA combination
Experimental: Crossover sequence 4; 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; Flovent is an ICS; Drug: Flovent Diskus® 250 mcg; Flovent is an ICS; Drug: Advair Diskus® 100/50 mcg; Advair is an ICS/LABA combination; Drug: Advair Diskus® 250/50 mcg; Advair is an ICS/LABA combination
Experimental: Crossover sequence 5; 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; Flovent is an ICS; Drug: Flovent Diskus® 500 mcg; Flovent is an ICS; Drug: Advair Diskus® 100/50 mcg; Advair is an ICS/LABA combination; Drug: Advair Diskus® 250/50 mcg; Advair is an ICS/LABA combination
Experimental: Crossover sequence 6; 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; Flovent is an ICS; Drug: Flovent Diskus® 500 mcg; Flovent is an ICS; Drug: Advair Diskus® 100/50 mcg; Advair is an ICS/LABA combination; Drug: Advair Diskus® 250/50 mcg; Advair is an ICS/LABA combination
Experimental: Crossover sequence 7; 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; Flovent is an ICS; Drug: Flovent Diskus® 500 mcg; Flovent is an ICS; Drug: Advair Diskus® 100/50 mcg; Advair is an ICS/LABA combination; Drug: Advair Diskus® 250/50 mcg; Advair is an ICS/LABA combination
Experimental: Crossover sequence 8; 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; Flovent is an ICS; Drug: Flovent Diskus® 500 mcg; Flovent is an ICS; Drug: Advair Diskus® 100/50 mcg; Advair is an ICS/LABA combination; Drug: Advair Diskus® 250/50 mcg; Advair is an ICS/LABA combination

Outcome Measures

Primary Outcome Measures :

1. 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. [ Time Frame: The last 12 weeks of each 14-week treatment period ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 5 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Arizona

University of Arizona College of Medicine

Tucson, Arizona, United States, 85724

United States, California

Children's Hospital & Research Center Oakland

Oakland, California, United States, 94609

UCSF Benioff Children's Hospital

San Francisco, California, United States, 94143

University of California - San Francisco

San Francisco, California, United States, 94143

United States, Colorado

National Jewish Health

Denver, Colorado, United States, 80206

United States, Florida

Nemours Children's Clinic

Jacksonville, Florida, United States, 32207

Nemours Children's Clinic

Orlando, Florida, United States, 32827

United States, Georgia

Emory University

Atlanta, Georgia, United States, 30322

United States, Illinois

Northwestern Memorial Hospital

Chicago, Illinois, United States, 60611

Rush University Medical Center

Chicago, Illinois, United States, 60612

University of Illinois at Chicago

Chicago, Illinois, United States, 60612

Ann and Robert H. Lurie Children's Hospital

Chicago, Illinois, United States, 60614

University of Chicago

Chicago, Illinois, United States, 60637

United States, Massachusetts

Brigham & Women's Hospital

Boston, Massachusetts, United States, 02115

Children's Hospital Boston

Boston, Massachusetts, United States, 02115

United States, Missouri

St. Louis Children's Hospital

Saint Louis, Missouri, United States, 63110

Washington University

Saint Louis, Missouri, United States, 63110

United States, New Mexico

University of New Mexico

Albuquerque, New Mexico, United States, 87131

United States, New York

Columbia University Medical Center

New York, New York, United States, 10032

United States, North Carolina

Duke University School of Medicine

Durham, North Carolina, United States, 27110

North Carolina Clinical Research

Raleigh, North Carolina, United States, 27607

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States, 27157

United States, Ohio

Rainbow Babies and Children's Hospital, Case Western Reserve University

Cleveland, Ohio, United States, 44106

United States, Pennsylvania

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States, 15212

University of Pittsburgh

Pittsburgh, Pennsylvania, United States, 15213

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States, 15224

United States, Wisconsin

University of Wisconsin-Madison

Madison, Wisconsin, United States, 53792

Center for Urban Population Health

Milwaukee, Wisconsin, United States, 53223

Sponsors and Collaborators

Milton S. Hershey Medical Center

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Study Chair: William Busse, MD; University of Wisconsin, Madison

  Study Documents (Full-Text)

Documents provided by dave mauger, Milton S. Hershey Medical Center:

Study Protocol and Statistical Analysis Plan  [PDF] July 21, 2017

More Information

Additional Information:

AsthmaNet 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: dave mauger, Principal Investigator, AsthmaNet Data Coordinating Center, Milton S. Hershey Medical Center
• ClinicalTrials.gov Identifier: NCT01967173
• Other Study ID Numbers: AsthmaNet 006; 1U10HL098115 ( U.S. NIH Grant/Contract )
• First Posted: October 22, 2013
• Results First Posted: November 15, 2018
• Last Update Posted: November 15, 2018
• Last Verified: October 2018

Keywords provided by dave mauger, Milton S. Hershey Medical Center:

Asthma; Fluticasone; Salmeterol

Additional relevant MeSH terms:

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