Best African American Response to Asthma Drugs

NCT01967173 | Completed Phase 3 Results DMC

• 2 other identifiers: AsthmaNet 0061U10HL098115
• Study Type: interventional
• Target: 574
• Locations: 1 country
• Sites: 28

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.

Conditions

Asthma

Keywords

Asthma; Fluticasone; Salmeterol

Outcome Measures

Primary Outcomes (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.

  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

Study Arms (8)

Crossover sequence 1

EXPERIMENTAL

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

Crossover sequence 2

EXPERIMENTAL

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

Crossover sequence 3

EXPERIMENTAL

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

Crossover sequence 4

EXPERIMENTAL

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

Crossover sequence 5

EXPERIMENTAL

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

Crossover sequence 6

EXPERIMENTAL

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

Crossover sequence 7

EXPERIMENTAL

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

Crossover sequence 8

EXPERIMENTAL

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

Interventions

Flovent Diskus® 100 mcg DRUG

Flovent is an ICS

Crossover sequence 1; Crossover sequence 2; Crossover sequence 3; Crossover sequence 4

Flovent Diskus® 250 mcg DRUG

Flovent is an ICS

Crossover sequence 1; Crossover sequence 2; Crossover sequence 3; Crossover sequence 4; Crossover sequence 5; Crossover sequence 6; Crossover sequence 7; Crossover sequence 8

Flovent Diskus® 500 mcg DRUG

Flovent is an ICS

Crossover sequence 5; Crossover sequence 6; Crossover sequence 7; Crossover sequence 8

Advair Diskus® 100/50 mcg DRUG

Advair is an ICS/LABA combination

Crossover sequence 1; Crossover sequence 2; Crossover sequence 3; Crossover sequence 4; Crossover sequence 5; Crossover sequence 6; Crossover sequence 7; Crossover sequence 8

Advair Diskus® 250/50 mcg DRUG

Advair is an ICS/LABA combination

Crossover sequence 1; Crossover sequence 2; Crossover sequence 3; Crossover sequence 4; Crossover sequence 5; Crossover sequence 6; Crossover sequence 7; Crossover sequence 8

Eligibility Criteria

• Age: 5 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Milton S. Hershey Medical Center: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (28)

University of Arizona College of Medicine

Tucson, Arizona, 85724, United States

Location

Children's Hospital & Research Center Oakland

Oakland, California, 94609, United States

Location

UCSF Benioff Children's Hospital

San Francisco, California, 94143, United States

Location

University of California - San Francisco

San Francisco, California, 94143, United States

Location

National Jewish Health

Denver, Colorado, 80206, United States

Location

Nemours Children's Clinic

Jacksonville, Florida, 32207, United States

Location

Nemours Children's Clinic

Orlando, Florida, 32827, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Illinois at Chicago

Chicago, Illinois, 60612, United States

Location

Ann and Robert H. Lurie Children's Hospital

Chicago, Illinois, 60614, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Brigham & Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Children's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

St. Louis Children's Hospital

St Louis, Missouri, 63110, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

University of New Mexico

Albuquerque, New Mexico, 87131, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Duke University School of Medicine

Durham, North Carolina, 27110, United States

Location

North Carolina Clinical Research

Raleigh, North Carolina, 27607, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

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

Cleveland, Ohio, 44106, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

University of Wisconsin-Madison

Madison, Wisconsin, 53792, United States

Location

Center for Urban Population Health

Milwaukee, Wisconsin, 53223, United States

Location

Related Publications (1)

• 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.

  PMID: 31553835 DERIVED

Related Links

• AsthmaNet

MeSH Terms

Conditions

Asthma

Interventions

Fluticasone; Fluticasone-Salmeterol Drug Combination

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Androstadienes; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Salmeterol Xinafoate; Albuterol; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: David Mauger
• Organization: Penn State University

dmauger@psu.edu

717-531-7178

Study Officials

• William Busse, MD

  University of Wisconsin, Madison

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, AsthmaNet Data Coordinating Center

Study Record Dates

• First Submitted: October 11, 2013
• First Posted: October 22, 2013
• Study Start: February 1, 2014
• Primary Completion: July 1, 2017
• Study Completion: July 1, 2017
• Last Updated: November 15, 2018
• Results First Posted: November 15, 2018

Record last verified: 2018-10

Locations

US (28)