Long-acting Beta Agonist Step Down Study

Phase 4

Completed

Conditions: Asthma

Interventions: Drug: Fluticasone/Salmeterol Diskus
Drug: Fluticasone Diskus

Registration Number: NCT01437995

Lead Sponsor: Johns Hopkins University

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 459

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Fluticasone/Salmeterol Diskus 250/50 ug	Fluticasone/Salmeterol Diskus	Continuation of Fluticasone/Salmeterol Diskus 250/50 ug twice daily
Fluticasone/Salmeterol Diskus 100/50 ug	Fluticasone/Salmeterol Diskus	Reduced dose Fluticasone/Salmeterol Diskus 100/50 ug twice daily
Fluticasone Diskus alone 250 ug	Fluticasone Diskus	Fluticasone Diskus alone 250 ug twice daily without Salmeterol

Primary Outcome Measures

Name	Time	Method
Treatment Failure	48 weeks	Rate of treatment failures assessed by decline in peak flow or FEV1, increased need for beta agonists, requirement for non-scheduled medical care for asthma symptoms, or prednisone taper.

Secondary Outcome Measures

Name	Time	Method
Pulmonary Function- Change in Peak Expiratory Flow	Baseline and 48 weeks	Change in morning peak expiratory flow rate from the patients' daily diary cards, calculated at 48 weeks minus baseline (randomization)
Rate of Episodes of Poor Asthma Control	48 weeks	Rate of episodes of poor asthma control (EPAC) defined by unscheduled medical care, hospitalization, use of oral corticosteroids and/or increased use of rescue medications and/or decrease of 30% or more in morning peak expiratory flow rate
Change in Pulmonary Function: FEV1 and FVC	Baseline and 48 weeks	Change in participant's pre-bronchodilator pulmonary function tests (FEV1 and FVC) calculated as 48 weeks minus baseline.
Pulmonary Function: Change in FEV1/FVC Ratio	Baseline and 48 weeks	Change in participant's FEV1/FVC ratio calculated as 48 weeks minus baseline.

Trial Locations

Locations (19): Washington University/St. Louis University
🇺🇸
St. Louis, Missouri, United States
The Ohio State University Medical Center
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Columbus, Ohio, United States
St. Vincent Healthcare
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Indianapolis, Indiana, United States
Duke University Medical Center
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Durham, North Carolina, United States
University of Arizona, Arizona Respiratory Center
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Tucson, Arizona, United States
University of Miami/University of South Florida
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Tampa, Florida, United States
National Jewish Health
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Denver, Colorado, United States
University of California, San Diego
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San Diego, California, United States
St. Vincent Hospital and Health Care Center, Inc
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Indianapolis, Indiana, United States
New York University School of Medicine
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New York, New York, United States
Louisiana State University Health Sciences Center, The Ernest N. Morial Asthma, Allergy and Respiratory Disease Center
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New Orleans, Louisiana, United States
Hofstra North Shore-LIJ School of Medicine
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New Hyde Park, New York, United States
University of Missouri, Kansas City School of Medicine
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Kansas City, Missouri, United States
Maria Fareri Children's Hospital at Westchester Medical Center and New York Medical College
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Valhalla, New York, United States
Northern New England Consortium
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Colchester, Vermont, United States
Baylor College of Medicine
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Houston, Texas, United States
The Illinois Consortium
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Chicago, Illinois, United States
Nemours Children's Clinic
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Jacksonville, Florida, United States
University of Virginia
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Charlottesville, Virginia, United States