The Leukotriene Modifier Or Corticosteroid or Corticosteroid-Salmeterol Trial

This research study will compare the treatment effects of three different asthma medications in asthma subjects whose asthma is well controlled when they take fluticasone, an inhaled corticosteroid. The treatments are fluticasone, montelukast (an anti?leukotriene drug), and a combination therapy of fluticasone and salmeterol (a long-acting beta-agonist). Fluticasone, montelukast, and the combination therapy of fluticasone and salmeterol (Advair Diskus®) are all approved for the treatment of asthma. We are looking at whether the three treatments are equally effective for reducing the number and the severity of asthma attacks in subjects with mild to moderately severe asthma.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: fluticasone; Drug: montelukast; Drug: Fluticasone plus salmeterol

Detailed Description

This trial will attempt to investigate whether asthmatic patients that are well controlled with low-dose twice daily inhaled corticosteroid (ICS) therapy can safely be switched to other modes of controller therapy without loss of asthma control. Patients demonstrating good control on twice-daily low-dose ICS will be randomized to one of three treatment groups: once-daily low-dose ICS (fluticasone), leukotriene receptor antagonist (montelukast), or once-daily combination therapy (fluticasone-salmeterol).

• Study Type: Interventional
• Enrollment (Actual): 500
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Hospital
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Nemour's Childrens Center
    • Miami, Florida, United States, 33136
      • University of Miami (and University of South Florida in Tampa)
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Illinois Consortium (Northwestern, Univ. of Chicago, Univ. of Illinois)
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Louisiana State University
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • University of Missouri at Kansas City
    • St. Louis, Missouri, United States, 63110
      • Washington University
  • New York
    • New Hyde Park, New York, United States, 11040
      • Long Island Jewish Hospital (and North Shore Hospital)
    • New York, New York, United States, 10016
      • New York Consortium (New York Univ. and Columbia Univ.)
    • Valhalla, New York, United States, 10595
      • New York Medical College
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University School of Medicine
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
  • Vermont
    • Burlington, Vermont, United States, 05405
      • Northern New England Consortium (Univ. of Vermont and other locations)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• physician-diagnosed asthma
• age 6 or older
• pre-bronchodilator forced expiratory volume (FEV1) of at least 60% of predicted
• beta-agonist reversibility OR airways hyperreactivity by methacholine challenge
• Juniper Asthma Control Score of 1.5 or greater if not on daily controller
• good current health

Exclusion Criteria:

• current or past smoking (greater than 20 pack-years)
• chronic or current oral steroid therapy
• pregnancy, lack of effective contraception (when appropriate), lactation

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Fluticasone; Participants continued fluticasone (100 microgram twice daily) treatment.	Drug: fluticasone; fluticasone (100 microgram twice daily) treatment; Drug: montelukast; Montelukast (5 or 10 mg each night).; Drug: Fluticasone plus salmeterol; fluticasone (100 microgram) plus salmeterol (50 microgram) each night
Experimental: Montelukast; Participants were changed to Montelukast (5 or 10 mg each night).	Drug: fluticasone; fluticasone (100 microgram twice daily) treatment; Drug: montelukast; Montelukast (5 or 10 mg each night).; Drug: Fluticasone plus salmeterol; fluticasone (100 microgram) plus salmeterol (50 microgram) each night
Experimental: Fluticasone plus salmeterol; Participants were given fluticasone (100 microgram) plus salmeterol (50 microgram) each night.	Drug: fluticasone; fluticasone (100 microgram twice daily) treatment; Drug: montelukast; Montelukast (5 or 10 mg each night).; Drug: Fluticasone plus salmeterol; fluticasone (100 microgram) plus salmeterol (50 microgram) each night

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Failure	The primary outcome measure was treatment failure, defined as the occurrence of any one of the following events: hospitalization or an urgent medical visit for asthma initiated by the patient or physician; use of systemic corticosteroids for asthma or need for open-label use of inhaled corticosteroids for asthma, as determined by the study physician or an asthma care provider; a decrease in prebronchodilator forced expiratory volume in 1 second (FEV1) to more than 20% below the baseline value measured at randomization; a decrease in the morning peak expiratory flow rate to more than 35% below the baseline value (the mean over the final 2 weeks of the run-in period) on 2 consecutive days; use of 10 puffs or more per day of rescue beta-agonist for 2 consecutive days (except as medication before exercise); refusal of the patient to continue because of lack of satisfaction with treatment; or judgment by a physician that the patient should stop treatment for reasons of safety.	16 weeks

Collaborators and Investigators

• Sponsor: JHSPH Center for Clinical Trials
• Collaborators: GlaxoSmithKline
• Investigators: Study Chair: Nicholas Anthonisen, MD, University of Winnipeg

Publications and helpful links

General Publications

• Duan QL, Gaume BR, Hawkins GA, Himes BE, Bleecker ER, Klanderman B, Irvin CG, Peters SP, Meyers DA, Hanrahan JP, Lima JJ, Litonjua AA, Tantisira KG, Liggett SB. Regulatory haplotypes in ARG1 are associated with altered bronchodilator response. Am J Respir Crit Care Med. 2011 Feb 15;183(4):449-54. doi: 10.1164/rccm.201005-0758OC. Epub 2010 Sep 17.
• Lang JE, Hossain J, Dixon AE, Shade D, Wise RA, Peters SP, Lima JJ; American Lung Association-Asthma Clinical Research Centers. Does age impact the obese asthma phenotype? Longitudinal asthma control, airway function, and airflow perception among mild persistent asthmatics. Chest. 2011 Dec;140(6):1524-1533. doi: 10.1378/chest.11-0675. Epub 2011 Jul 28.
• American Lung Association Asthma Clinical Research Centers; Peters SP, Anthonisen N, Castro M, Holbrook JT, Irvin CG, Smith LJ, Wise RA. Randomized comparison of strategies for reducing treatment in mild persistent asthma. N Engl J Med. 2007 May 17;356(20):2027-39. doi: 10.1056/NEJMoa070013. Erratum In: N Engl J Med. 2007 Aug 16;357(7):728.

Helpful Links

• American Lung Association Asthma Clinical Research Centers

Study record dates

Study Major Dates

• Study Start: June 1, 2003
• Primary Completion (Actual): August 1, 2005
• Study Completion (Actual): August 1, 2006

Study Registration Dates

• First Submitted: September 8, 2005
• First Submitted That Met QC Criteria: September 8, 2005
• First Posted (Estimate): September 12, 2005

Study Record Updates

• Last Update Posted (Estimate): December 9, 2015
• Last Update Submitted That Met QC Criteria: November 4, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: Asthma; Asthma Control
• 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; Hormones, Hormone Substitutes, and Hormone Antagonists; Adrenergic Agonists; Dermatologic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Leukotriene Antagonists; Hormone Antagonists; Cytochrome P-450 CYP1A2 Inducers; Cytochrome P-450 Enzyme Inducers; Anti-Allergic Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Montelukast; Fluticasone; Xhance; Salmeterol Xinafoate
• Other Study ID Numbers: ALAACRC-03