Long-acting Beta Agonist Step Down Study (LASST)

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.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Fluticasone/Salmeterol Diskus; Drug: Fluticasone/Salmeterol Diskus; Drug: Fluticasone Diskus

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.

• Study Type: Interventional
• Enrollment (Actual): 459
• Phase: Phase 4

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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: Salmeterol; Fluticasone; Drug: Fluticasone/Salmeterol Diskus; Reduced dose Fluticasone/Salmeterol Diskus 100/50 ug twice daily; Other Names: Salmeterol; Fluticasone
Active Comparator: Fluticasone/Salmeterol Diskus 100/50 ug; Reduced dose Fluticasone/Salmeterol Diskus 100/50 ug twice daily	Drug: Fluticasone/Salmeterol Diskus; Continuation of Fluticasone/Salmeterol Diskus 250/50 ug twice daily; Other Names: Salmeterol; Fluticasone; Drug: Fluticasone/Salmeterol Diskus; Reduced dose Fluticasone/Salmeterol Diskus 100/50 ug twice daily; Other Names: Salmeterol; Fluticasone
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 Names: Fluticasone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Failure	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.	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pulmonary Function- Change in Peak Expiratory Flow	Change in morning peak expiratory flow rate from the patients' daily diary cards, calculated at 48 weeks minus baseline (randomization)	Baseline and 48 weeks
Rate of Episodes of Poor Asthma Control	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	48 weeks
Change in Pulmonary Function: FEV1 and FVC	Change in participant's pre-bronchodilator pulmonary function tests (FEV1 and FVC) calculated as 48 weeks minus baseline.	Baseline and 48 weeks
Pulmonary Function: Change in FEV1/FVC Ratio	Change in participant's FEV1/FVC ratio calculated as 48 weeks minus baseline.	Baseline and 48 weeks

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: GlaxoSmithKline; American Lung Association
• Investigators: Study Director: Robert A Wise, MD, Johns Hopkins University; Principal Investigator: Linda Rogers, MD, NYU Langone Health

Publications and helpful links

General Publications

• 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.

Helpful Links

• American Lung Association

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): October 1, 2015

Study Registration Dates

• First Submitted: September 5, 2011
• First Submitted That Met QC Criteria: September 20, 2011
• First Posted (Estimate): September 21, 2011

Study Record Updates

• Last Update Posted (Actual): April 25, 2017
• Last Update Submitted That Met QC Criteria: March 14, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Asthma; Inhaled corticosteroids; Step down therapy; Long-acting beta agonists; Fluticasone Salmeterol
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Adrenergic Agonists; Dermatologic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Sympathomimetics; Fluticasone; Xhance; Salmeterol Xinafoate; Fluticasone-Salmeterol Drug Combination
• Other Study ID Numbers: ADV115922