Long-acting Beta Agonist Step Down Study - Full Text View

Purpose

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.

Condition	Intervention	Phase
Asthma	Drug: Fluticasone/Salmeterol Diskus Drug: Fluticasone Diskus	Phase 4


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Participant, Care Provider, Investigator Primary Purpose: Treatment
Official Title:	Long-acting Beta Agonist Step Down Study

Resource links provided by NLM:

Drug Information available for: Fluticasone propionate Salmeterol Fluticasone Salmeterol xinafoate Fluticasone furoate

U.S. FDA Resources

Further study details as provided by Robert A. Wise, Johns Hopkins University:

Primary Outcome Measures:

Treatment Failure [ Time Frame: 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:

Pulmonary Function- Change in Peak Expiratory Flow [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Baseline and 48 weeks ]
Change in participant's FEV1/FVC ratio calculated as 48 weeks minus baseline.


Enrollment:	459
Study Start Date:	March 2012
Study Completion Date:	October 2015
Primary Completion Date:	September 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Fluticasone/Salmeterol Diskus 250/50 ug Continuation of Fluticasone/Salmeterol Diskus 250/50 ug twice daily	Drug: Fluticasone/Salmeterol Diskus Continuation of Fluticasone/Salmeterol Diskus 250/50 ug twice daily Other Names: Fluticasone Salmeterol
Active Comparator: Fluticasone/Salmeterol Diskus 100/50 ug Reduced dose Fluticasone/Salmeterol Diskus 100/50 ug twice daily	Drug: Fluticasone/Salmeterol Diskus Reduced dose Fluticasone/Salmeterol Diskus 100/50 ug twice daily Other Names: Fluticasone Salmeterol
Active Comparator: Fluticasone Diskus alone 250 ug Fluticasone Diskus alone 250 ug twice daily without Salmeterol	Drug: Fluticasone Diskus Fluticasone Diskus alone 250 ug twice daily without Salmeterol Other Name: Fluticasone

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


Ages Eligible for Study:	12 Years and older (Child, Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01437995

Locations


United States, Arizona
University of Arizona, Arizona Respiratory Center
Tucson, Arizona, United States, 85724
United States, California
University of California, San Diego
San Diego, California, United States, 92103
United States, Colorado
National Jewish Health
Denver, Colorado, United States, 80206
United States, Florida
Nemours Children's Clinic
Jacksonville, Florida, United States, 32207
University of Miami/University of South Florida
Tampa, Florida, United States, 33613
United States, Illinois
The Illinois Consortium
Chicago, Illinois, United States, 60611
United States, Indiana
St. Vincent Healthcare
Indianapolis, Indiana, United States, 46260
St. Vincent Hospital and Health Care Center, Inc
Indianapolis, Indiana, United States, 46290
United States, Louisiana
Louisiana State University Health Sciences Center, The Ernest N. Morial Asthma, Allergy and Respiratory Disease Center
New Orleans, Louisiana, United States, 70112
United States, Missouri
University of Missouri, Kansas City School of Medicine
Kansas City, Missouri, United States, 64108
Washington University/St. Louis University
St. Louis, Missouri, United States, 63110
United States, New York
Hofstra North Shore-LIJ School of Medicine
New Hyde Park, New York, United States, 11040
New York University School of Medicine
New York, New York, United States, 10016
Maria Fareri Children's Hospital at Westchester Medical Center and New York Medical College
Valhalla, New York, United States, 10595
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
The Ohio State University Medical Center
Columbus, Ohio, United States, 43221
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
United States, Vermont
Northern New England Consortium
Colchester, Vermont, United States, 05446
United States, Virginia
University of Virginia
Charlottesville, Virginia, United States, 22908

Sponsors and Collaborators

Johns Hopkins University

American Lung Association

GlaxoSmithKline

Investigators


Study Director:	Robert A Wise, MD	Johns Hopkins University
Principal Investigator:	Linda Rogers, MD	New York University School of Medicine

More Information

Additional Information:

American Lung Association This link exits the ClinicalTrials.gov site


Responsible Party:	Robert A. Wise, Professor of Medicine, Johns Hopkins University
ClinicalTrials.gov Identifier:	NCT01437995 History of Changes
Other Study ID Numbers:	ADV115922
Study First Received:	September 5, 2011
Results First Received:	October 7, 2016
Last Updated:	March 14, 2017

Keywords provided by Robert A. Wise, Johns Hopkins University:


Asthma Step down therapy Inhaled corticosteroids Long-acting beta agonists Fluticasone Salmeterol

Additional relevant MeSH terms:


Fluticasone Salmeterol Xinafoate Fluticasone Propionate, Salmeterol Xinafoate Drug Combination Anti-Inflammatory Agents Bronchodilator Agents Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Anti-Asthmatic Agents Respiratory System Agents Dermatologic Agents	Anti-Allergic Agents Adrenergic beta-2 Receptor Agonists Adrenergic beta-Agonists Adrenergic Agonists Adrenergic Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Sympathomimetics

ClinicalTrials.gov processed this record on June 23, 2017

Long-acting Beta Agonist Step Down Study (LASST)