Clinical trial NCT01437995: Long-acting Beta Agonist Step Down Study
Official title: Long-acting Beta Agonist Step Down Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Asthma
Keywords: Asthma
Step down therapy
Inhaled corticosteroids
Long-acting beta agonists
Fluticasone Salmeterol
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: American Lung Association
name: GlaxoSmithKline
First posted: 2011-09-21
Enrollment: 459
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Treatment Failure
timeFrame: 48 weeks
Secondary outcomes:
measure: Pulmonary Function- Change in Peak Expiratory Flow
timeFrame: Baseline and 48 weeks
measure: Rate of Episodes of Poor Asthma Control
timeFrame: 48 weeks
measure: Change in Pulmonary Function: FEV1 and FVC
timeFrame: Baseline and 48 weeks
measure: Pulmonary Function: Change in FEV1/FVC Ratio
timeFrame: Baseline and 48 weeks
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona, Arizona Respiratory Center
state: Arizona
city: San Diego
country: United States
facility: University of California, San Diego
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: Tampa
country: United States
facility: University of Miami/University of South Florida
state: Florida
city: Chicago
country: United States
facility: The Illinois Consortium
state: Illinois
city: Indianapolis
country: United States
facility: St. Vincent Healthcare
state: Indiana
city: Indianapolis
country: United States
facility: St. Vincent Hospital and Health Care Center, Inc
state: Indiana
city: New Orleans
country: United States
facility: Louisiana State University Health Sciences Center, The Ernest N. Morial Asthma, Allergy and Respiratory Disease Center
state: Louisiana
city: Kansas City
country: United States
facility: University of Missouri, Kansas City School of Medicine
state: Missouri
city: St. Louis
country: United States
facility: Washington University/St. Louis University
state: Missouri
city: New Hyde Park
country: United States
facility: Hofstra North Shore-LIJ School of Medicine
state: New York
city: New York
country: United States
facility: New York University School of Medicine
state: New York
city: Valhalla
country: United States
facility: Maria Fareri Children's Hospital at Westchester Medical Center and New York Medical College
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University Medical Center
state: Ohio
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Colchester
country: United States
facility: Northern New England Consortium
state: Vermont
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
Study officials:
affiliation: Johns Hopkins University
name: Robert A Wise, MD
role: STUDY_DIRECTOR
affiliation: NYU Langone Health
name: Linda Rogers, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.