Long-acting Beta Agonist Step Down Study

NCT ID: NCT01437995

Last Updated: 2017-04-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 459 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-03-31
• Study Completion Date: 2015-10-31

Brief Summary

This study is a 56-week, multi-center, blinded, randomized, double-masked parallel group comparative effectiveness study of approaches to stepping down therapy for patients with well-controlled asthma treated with combination ICS and LABA.

Detailed Description

Current asthma guidelines recommend stepping down therapy once asthma is controlled for at least 3 months. For patients treated with inhaled corticosteroids (ICS) alone, a dose reduction of 25-50% to a minimal dose that controls disease is recommended. The optimal approach to reducing treatment in patients with asthma treated with combination inhaled corticosteroids and long-acting beta agonists (ICS/LABA) is not clear. The American Lung Association Asthma Clinical Research Center (ALAACRC) is a network of 18 asthma research centers with the goal of performing clinical trials directly relevant to clinical practice. The question of the optimal way to de-escalate therapy in patients with asthma that is well controlled on fixed dose combination ICS/LABA is a key question for practitioners caring for patients with moderate to severe persistent asthma. We propose a 56 week multi-center, prospective, randomized, three-arm parallel group comparative effectiveness study comparing three approaches to care of patients with asthma well-controlled for three months on combination ICS/LABA: reduction of ICS dose and maintenance of LABA, initial discontinuation of LABA with continuation of ICS, and continuation of stable dose ICS/LABA. Our primary goal is to perform a pragmatic study that resembles clinical practice and determine the optimal treatment strategy that results in the lowest rate of treatment failure over 48 weeks of follow-up. Additional exploratory analyses include assessing risk factors for step-down failure, and to assess the duration of time that asthma control is maintained when therapy is de-escalated.

Conditions

Asthma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Fluticasone/Salmeterol Diskus 250/50 ug

Continuation of Fluticasone/Salmeterol Diskus 250/50 ug twice daily

Group Type: ACTIVE_COMPARATOR

Fluticasone/Salmeterol Diskus

Intervention Type: DRUG

Continuation of Fluticasone/Salmeterol Diskus 250/50 ug twice daily

Fluticasone/Salmeterol Diskus 100/50 ug

Reduced dose Fluticasone/Salmeterol Diskus 100/50 ug twice daily

Group Type: ACTIVE_COMPARATOR

Fluticasone/Salmeterol Diskus

Intervention Type: DRUG

Reduced dose Fluticasone/Salmeterol Diskus 100/50 ug twice daily

Fluticasone Diskus alone 250 ug

Fluticasone Diskus alone 250 ug twice daily without Salmeterol

Group Type: ACTIVE_COMPARATOR

Fluticasone Diskus

Intervention Type: DRUG

Fluticasone Diskus alone 250 ug twice daily without Salmeterol

Interventions

Fluticasone/Salmeterol Diskus

Continuation of Fluticasone/Salmeterol Diskus 250/50 ug twice daily

Intervention Type: DRUG

Fluticasone/Salmeterol Diskus

Reduced dose Fluticasone/Salmeterol Diskus 100/50 ug twice daily

Intervention Type: DRUG

Fluticasone Diskus

Fluticasone Diskus alone 250 ug twice daily without Salmeterol

Intervention Type: DRUG

Other Intervention Names

Fluticasone; Salmeterol; Fluticasone; Salmeterol; Fluticasone

Eligibility Criteria

Inclusion Criteria

• age 12-80 years
• physician diagnosed asthma that is well-controlled on moderate dose ICS/LABA based on an Asthma Control Test (ACT) score more than or equal to 20, and the absence of unscheduled visits or use of rescue prednisone for 4 weeks prior to enrollment
• pre-bronchodilator FEV1 (forced expiratory volume in 1 second) more than or equal to 70% predicted

Exclusion Criteria

• chronic oral steroid therapy
• hospitalization or urgent care visit within 4 weeks of the screening visit
• lung disease other than asthma including COPD, bronchiectasis, sarcoidosis or other lung disease
• less than 10 pack/yr of tobacco use and abstinence for at least 1 yr
• history of extensive environmental tobacco exposure or occupational exposure suggestive of possible COPD (chronic obstructive pulmonary disease) per judgment of investigator
• post bronchodilator FEV1 less than 70% predicted
• near fatal asthma (intubation or ICU admission for asthma) within 2 yrs of enrollment
• high risk of near fatal or fatal asthma
• history of known premature birth less than 33 weeks or any significant level of respiratory care including prolonged oxygen administration or mechanical ventilation during the neonatal period
• unstable cardiac disease (decompensated congestive heart failure, unstable angina, recent myocardial infarction, atrial fibrillation, supraventricular or ventricular tachycardia, congenital heart disease, or severe uncontrolled hypertension)
• other major chronic illnesses which in the judgment of the study physician would interfere with participation in the study e.g. including but not limited to uncontrolled diabetes, uncontrolled HIV infection or other immune system disorder
• drug allergies to any component of study drug or history of adverse reaction to short or long acting beta agonists
• for women of child bearing potential; not pregnant, not lactating and agree to practice an adequate birth control method (abstinence, combination barrier and spermicide, or hormonal) for the duration of the study

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

American Lung Association

OTHER

Sponsor Role: collaborator

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

Johns Hopkins University

OTHER

Sponsor Role: lead

Responsible Party

Robert A. Wise

Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Robert A Wise, MD

Role: STUDY_DIRECTOR

Johns Hopkins University

Linda Rogers, MD

Role: PRINCIPAL_INVESTIGATOR

NYU Langone Health

Locations

University of Arizona, Arizona Respiratory Center

Tucson, Arizona, United States

University of California, San Diego

San Diego, California, United States

National Jewish Health

Denver, Colorado, United States

Nemours Children's Clinic

Jacksonville, Florida, United States

University of Miami/University of South Florida

Tampa, Florida, United States

The Illinois Consortium

Chicago, Illinois, United States

St. Vincent Healthcare

Indianapolis, Indiana, United States

St. Vincent Hospital and Health Care Center, Inc

Indianapolis, Indiana, United States

Louisiana State University Health Sciences Center, The Ernest N. Morial Asthma, Allergy and Respiratory Disease Center

New Orleans, Louisiana, United States

University of Missouri, Kansas City School of Medicine

Kansas City, Missouri, United States

Washington University/St. Louis University

St Louis, Missouri, United States

Hofstra North Shore-LIJ School of Medicine

New Hyde Park, New York, United States

New York University School of Medicine

New York, New York, United States

Maria Fareri Children's Hospital at Westchester Medical Center and New York Medical College

Valhalla, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

The Ohio State University Medical Center

Columbus, Ohio, United States

Baylor College of Medicine

Houston, Texas, United States

Northern New England Consortium

Colchester, Vermont, United States

University of Virginia

Charlottesville, Virginia, United States

Countries

United States

References

Blake KV, Antal H, Bunnell HT, He J, Henderson R, Holbrook JT, McCahan SM, Pennington C, Rogers L, Shade D, Sugar EA, Taylor A, Wise RA, Wysocki T. Comprehension by Caregivers and Adolescents of Clinical Trial Information Delivered via Multimedia Video Versus Conventional Practice: Nonrandomized Controlled Trial. JMIR Pediatr Parent. 2023 Jun 22;6:e44252. doi: 10.2196/44252.

Reference Type: DERIVED

PMID: 37347518 (View on PubMed)

DiMango E, Rogers L, Reibman J, Gerald LB, Brown M, Sugar EA, Henderson R, Holbrook JT. Risk Factors for Asthma Exacerbation and Treatment Failure in Adults and Adolescents with Well-controlled Asthma during Continuation and Step-Down Therapy. Ann Am Thorac Soc. 2018 Aug;15(8):955-961. doi: 10.1513/AnnalsATS.201711-886OC.

Reference Type: DERIVED

PMID: 29863899 (View on PubMed)

Related Links

http://www.lungusa.org/

American Lung Association

Other Identifiers

ADV115922

Identifier Type: -

Identifier Source: org_study_id