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LASST: Long-acting Beta Agonist Step Down Study

Sponsor
Johns Hopkins University (Other)
Overall Status
Completed
CT.gov ID
NCT01437995
Collaborator
American Lung Association (Other), GlaxoSmithKline (Industry)
459
Enrollment
19
Locations
3
Arms
43
Duration (Months)
24.2
Patients Per Site
0.6
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Fluticasone/Salmeterol Diskus
  • Drug: Fluticasone/Salmeterol Diskus
  • Drug: Fluticasone Diskus
 Phase 4

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 Design

Study Type:
Interventional
Actual Enrollment :
459 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
Long-acting Beta Agonist Step Down Study
Study Start Date :
Mar 1, 2012
Actual Primary Completion Date :
Sep 1, 2015
Actual Study Completion Date :
Oct 1, 2015

Arms and Interventions

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:
  • 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 Names:
  • Fluticasone

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 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

    1. 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)

    2. 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

    3. 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.

    4. Pulmonary Function: Change in FEV1/FVC Ratio [Baseline and 48 weeks]

      Change in participant's FEV1/FVC ratio calculated as 48 weeks minus baseline.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    12 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Locations

    Site City State Country Postal Code
    1 University of Arizona, Arizona Respiratory Center Tucson Arizona United States 85724
    2 University of California, San Diego San Diego California United States 92103
    3 National Jewish Health Denver Colorado United States 80206
    4 Nemours Children's Clinic Jacksonville Florida United States 32207
    5 University of Miami/University of South Florida Tampa Florida United States 33613
    6 The Illinois Consortium Chicago Illinois United States 60611
    7 St. Vincent Healthcare Indianapolis Indiana United States 46260
    8 St. Vincent Hospital and Health Care Center, Inc Indianapolis Indiana United States 46290
    9 Louisiana State University Health Sciences Center, The Ernest N. Morial Asthma, Allergy and Respiratory Disease Center New Orleans Louisiana United States 70112
    10 University of Missouri, Kansas City School of Medicine Kansas City Missouri United States 64108
    11 Washington University/St. Louis University St. Louis Missouri United States 63110
    12 Hofstra North Shore-LIJ School of Medicine New Hyde Park New York United States 11040
    13 New York University School of Medicine New York New York United States 10016
    14 Maria Fareri Children's Hospital at Westchester Medical Center and New York Medical College Valhalla New York United States 10595
    15 Duke University Medical Center Durham North Carolina United States 27710
    16 The Ohio State University Medical Center Columbus Ohio United States 43221
    17 Baylor College of Medicine Houston Texas United States 77030
    18 Northern New England Consortium Colchester Vermont United States 05446
    19 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, NYU Langone Health

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Robert A. Wise, Professor of Medicine, Johns Hopkins University
    ClinicalTrials.gov Identifier:
    NCT01437995
    Other Study ID Numbers:
    • ADV115922
    First Posted:
    Sep 21, 2011
    Last Update Posted:
    Apr 25, 2017
    Last Verified:
    Mar 1, 2017
    Keywords provided by Robert A. Wise, Professor of Medicine, Johns Hopkins University
    Asthma
    Step down therapy
    Inhaled corticosteroids
    Long-acting beta agonists
    Fluticasone Salmeterol
    Additional relevant MeSH terms:
    Asthma
    Fluticasone
    Xhance
    Salmeterol Xinafoate
    Fluticasone-Salmeterol Drug Combination

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail Enrolled participants were enrolled in an 8-week open label treatment run-in and were subsequently randomized only if their asthma remained stable (i.e. an ACT score ≥ 20 at weeks 4 & 8, no unscheduled healthcare encounters, no change in asthma medication, pre-bronchodilator FEV1 ≥ 70% predicted, and limited use of rescue beta-agonist).
    Arm/Group Title Stable ICS-LABA Reduced ICS/LABA LABA Step Off
    Arm/Group Description Continuation of Fluticasone/Salmeterol Diskus 250/50 ug twice daily Fluticasone/Salmeterol Diskus: Continuation of Fluticasone/Salmeterol Diskus 250/50 ug twice daily Reduced dose Fluticasone/Salmeterol Diskus 100/50 ug twice daily Fluticasone/Salmeterol Diskus: Reduced dose Fluticasone/Salmeterol Diskus 100/50 ug twice daily Fluticasone Diskus alone 250 ug twice daily without Salmeterol Fluticasone Diskus: Fluticasone Diskus alone 250 ug twice daily without Salmeterol
    Period Title: Overall Study
    STARTED 151 149 155
    Included in Treatment Failure Analysis 150 146 151
    COMPLETED 140 131 135
    NOT COMPLETED 11 18 20

    Baseline Characteristics

    Arm/Group Title Stable ICS-LABA Reduced ICS/LABA LABA Step Off Total
    Arm/Group Description Continuation of Fluticasone/Salmeterol Diskus 250/50 ug twice daily Fluticasone/Salmeterol Diskus: Continuation of Fluticasone/Salmeterol Diskus 250/50 ug twice daily Reduced dose Fluticasone/Salmeterol Diskus 100/50 ug twice daily Fluticasone/Salmeterol Diskus: Reduced dose Fluticasone/Salmeterol Diskus 100/50 ug twice daily Fluticasone Diskus alone 250 ug twice daily without Salmeterol Fluticasone Diskus: Fluticasone Diskus alone 250 ug twice daily without Salmeterol Total of all reporting groups
    Overall Participants 151 149 155 455
    Age (years) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [years]
    36
    33
    35
    35
    Age, Customized (participants) [Number]
    <18
    31
    20.5%
    39
    26.2%
    30
    19.4%
    100
    22%
    >=18
    120
    79.5%
    110
    73.8%
    125
    80.6%
    355
    78%
    Sex: Female, Male (Count of Participants)
    Female
    96
    63.6%
    88
    59.1%
    103
    66.5%
    287
    63.1%
    Male
    55
    36.4%
    61
    40.9%
    52
    33.5%
    168
    36.9%
    Race/Ethnicity, Customized (participants) [Number]
    White
    72
    47.7%
    74
    49.7%
    75
    48.4%
    221
    48.6%
    Black
    52
    34.4%
    48
    32.2%
    51
    32.9%
    151
    33.2%
    Hispanic
    19
    12.6%
    23
    15.4%
    24
    15.5%
    66
    14.5%
    Other
    8
    5.3%
    4
    2.7%
    5
    3.2%
    17
    3.7%
    Region of Enrollment (participants) [Number]
    United States
    151
    100%
    149
    100%
    155
    100%
    455
    100%
    Smoke exposure (participants) [Number]
    Former smoker
    23
    15.2%
    25
    16.8%
    14
    9%
    62
    13.6%
    Secondhand smoke home/work
    18
    11.9%
    21
    14.1%
    17
    11%
    56
    12.3%
    Asthma characteristics (participants) [Number]
    Hospitalized for asthma in past year
    5
    3.3%
    3
    2%
    6
    3.9%
    14
    3.1%
    Oral steroids in past year
    44
    29.1%
    36
    24.2%
    42
    27.1%
    122
    26.8%
    Daily short-acting beta agonist use
    7
    4.6%
    12
    8.1%
    10
    6.5%
    29
    6.4%
    Daily anti-leukotriene use
    32
    21.2%
    30
    20.1%
    30
    19.4%
    92
    20.2%
    Age of Asthma Onset (years) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [years]
    7
    7
    7
    7
    eNO (exhaled nitric oxide) (parts per billion) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [parts per billion]
    18.5
    17.5
    16.5
    17.5
    Atopy (phadiatop ≥ 0.35 kUA/l) (participants) [Number]
    Number [participants]
    115
    76.2%
    123
    82.6%
    114
    73.5%
    352
    77.4%
    Asthma Symptom Utility Index (units on a scale) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [units on a scale]
    0.95
    0.94
    0.98
    0.95
    Pulmonary function measures (Liters) [Median (Inter-Quartile Range) ]
    Pre-bronchodilator FEV1
    2.82
    2.86
    2.82
    2.83
    Pre-bronchodilator FVC
    3.54
    3.62
    3.65
    3.62
    Post-bronchodilator FEV1
    2.88
    2.96
    2.93
    2.92
    Post-bronchodilator FVC
    3.59
    3.72
    3.65
    3.62
    Pulmonary function measures, percent predicted (percent predicted) [Median (Inter-Quartile Range) ]
    Pre-bronchodilator FEV1
    91
    91
    92
    91
    Pre-bronchodilator FVC
    98
    100
    98
    99
    Pre-bronchodilator peak flow
    96
    100
    98
    98
    Other conditions, based upon self-report (participants) [Number]
    Eczema
    35
    23.2%
    28
    18.8%
    26
    16.8%
    89
    19.6%
    Sinusitis
    50
    33.1%
    41
    27.5%
    34
    21.9%
    125
    27.5%
    Allergic rhinitis
    85
    56.3%
    73
    49%
    88
    56.8%
    246
    54.1%
    Food allergies
    33
    21.9%
    40
    26.8%
    34
    21.9%
    107
    23.5%
    Allergies worsen asthma
    123
    81.5%
    113
    75.8%
    122
    78.7%
    358
    78.7%
    Pre-bronchodilator peak flow (Liters per minute) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [Liters per minute]
    420
    430
    430
    430
    Asthma Control Test Score (units on a scale) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [units on a scale]
    23
    23
    23
    23
    Marks AQLQ (units on a scale) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [units on a scale]
    4.0
    5.0
    4.0
    4.0
    Children's Health Survey for Asthma - Child Version (units on a scale) [Median (Inter-Quartile Range) ]
    Physical
    93
    93
    96
    93
    Activity
    100
    100
    100
    100
    Emotional
    93
    95
    93
    93
    Euroqual EQ-5D-5L (units on a scale) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [units on a scale]
    1.00
    1.00
    1.00
    1.00

    Outcome Measures

    1. Primary Outcome
    Title Treatment Failure
    Description 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.
    Time Frame 48 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Stable ICS-LABA Reduced ICS/LABA LABA Step Off
    Arm/Group Description Continuation of Fluticasone/Salmeterol Diskus 250/50 ug twice daily Fluticasone/Salmeterol Diskus: Continuation of Fluticasone/Salmeterol Diskus 250/50 ug twice daily Reduced dose Fluticasone/Salmeterol Diskus 100/50 ug twice daily Fluticasone/Salmeterol Diskus: Reduced dose Fluticasone/Salmeterol Diskus 100/50 ug twice daily Fluticasone Diskus alone 250 ug twice daily without Salmeterol Fluticasone Diskus: Fluticasone Diskus alone 250 ug twice daily without Salmeterol
    Measure Participants 150 146 151
    Number [participants]
    38
    25.2%
    39
    26.2%
    45
    29%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Stable ICS-LABA, Reduced ICS/LABA, LABA Step Off
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.07
    Confidence Interval (2-Sided) 95.3%
    0.69 to 1.65
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Pulmonary Function- Change in Peak Expiratory Flow
    Description Change in morning peak expiratory flow rate from the patients' daily diary cards, calculated at 48 weeks minus baseline (randomization)
    Time Frame Baseline and 48 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Stable ICS-LABA Reduced ICS/LABA LABA Step Off
    Arm/Group Description Continuation of Fluticasone/Salmeterol Diskus 250/50 ug twice daily Fluticasone/Salmeterol Diskus: Continuation of Fluticasone/Salmeterol Diskus 250/50 ug twice daily Reduced dose Fluticasone/Salmeterol Diskus 100/50 ug twice daily Fluticasone/Salmeterol Diskus: Reduced dose Fluticasone/Salmeterol Diskus 100/50 ug twice daily Fluticasone Diskus alone 250 ug twice daily without Salmeterol Fluticasone Diskus: Fluticasone Diskus alone 250 ug twice daily without Salmeterol
    Measure Participants 150 146 151
    Median (95% Confidence Interval) [Liters per minute]
    -0.08
    4.40
    -14.16
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Stable ICS-LABA, Reduced ICS/LABA
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.43
    Comments
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Stable ICS-LABA, LABA Step Off
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.022
    Comments
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Reduced ICS/LABA, LABA Step Off
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    Comments
    Method Kruskal-Wallis
    Comments
    3. Secondary Outcome
    Title Rate of Episodes of Poor Asthma Control
    Description 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
    Time Frame 48 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Stable ICS-LABA Reduced ICS/LABA LABA Step Off
    Arm/Group Description Continuation of Fluticasone/Salmeterol Diskus 250/50 ug twice daily Fluticasone/Salmeterol Diskus: Continuation of Fluticasone/Salmeterol Diskus 250/50 ug twice daily Reduced dose Fluticasone/Salmeterol Diskus 100/50 ug twice daily Fluticasone/Salmeterol Diskus: Reduced dose Fluticasone/Salmeterol Diskus 100/50 ug twice daily Fluticasone Diskus alone 250 ug twice daily without Salmeterol Fluticasone Diskus: Fluticasone Diskus alone 250 ug twice daily without Salmeterol
    Measure Participants 152 147 153
    Number [Episodes of poor asthma control]
    183
    164
    219
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Stable ICS-LABA, Reduced ICS/LABA
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 0.93
    Confidence Interval (2-Sided) 95%
    0.63 to 1.41
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Stable ICS-LABA, LABA Step Off
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 1.18
    Confidence Interval (2-Sided) 95%
    0.80 to 1.73
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Reduced ICS/LABA, LABA Step Off
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 1.24
    Confidence Interval (2-Sided) 95%
    0.83 to 1.81
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title Change in Pulmonary Function: FEV1 and FVC
    Description Change in participant's pre-bronchodilator pulmonary function tests (FEV1 and FVC) calculated as 48 weeks minus baseline.
    Time Frame Baseline and 48 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Stable ICS-LABA Reduced ICS/LABA LABA Step Off
    Arm/Group Description Continuation of Fluticasone/Salmeterol Diskus 250/50 ug twice daily Fluticasone/Salmeterol Diskus: Continuation of Fluticasone/Salmeterol Diskus 250/50 ug twice daily Reduced dose Fluticasone/Salmeterol Diskus 100/50 ug twice daily Fluticasone/Salmeterol Diskus: Reduced dose Fluticasone/Salmeterol Diskus 100/50 ug twice daily Fluticasone Diskus alone 250 ug twice daily without Salmeterol Fluticasone Diskus: Fluticasone Diskus alone 250 ug twice daily without Salmeterol
    Measure Participants 150 146 151
    Pre-bronchodilator FEV1
    -0.02
    -0.07
    -0.13
    Pre-bronchodilator FVC
    -0.01
    -0.04
    -0.09
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Stable ICS-LABA, Reduced ICS/LABA
    Comments Comparing change in pre-bronchodilator FEV1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.15
    Comments
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Stable ICS-LABA, LABA Step Off
    Comments Comparing change in pre-bronchodilator FEV1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Reduced ICS/LABA, LABA Step Off
    Comments Comparing change in pre-bronchodilator FEV1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.027
    Comments
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Stable ICS-LABA, Reduced ICS/LABA
    Comments Comparison of change in pre-bronchodilator FVC
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.40
    Comments
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Stable ICS-LABA, LABA Step Off
    Comments Comparison of change in pre-bronchodilator FVC
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.032
    Comments
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Reduced ICS/LABA, LABA Step Off
    Comments Comparison of change in pre-bronchodilator FVC
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.21
    Comments
    Method Kruskal-Wallis
    Comments
    5. Secondary Outcome
    Title Pulmonary Function: Change in FEV1/FVC Ratio
    Description Change in participant's FEV1/FVC ratio calculated as 48 weeks minus baseline.
    Time Frame Baseline and 48 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Stable ICS-LABA Reduced ICS/LABA LABA Step Off
    Arm/Group Description Continuation of Fluticasone/Salmeterol Diskus 250/50 ug twice daily Fluticasone/Salmeterol Diskus: Continuation of Fluticasone/Salmeterol Diskus 250/50 ug twice daily Reduced dose Fluticasone/Salmeterol Diskus 100/50 ug twice daily Fluticasone/Salmeterol Diskus: Reduced dose Fluticasone/Salmeterol Diskus 100/50 ug twice daily Fluticasone Diskus alone 250 ug twice daily without Salmeterol Fluticasone Diskus: Fluticasone Diskus alone 250 ug twice daily without Salmeterol
    Measure Participants 150 146 151
    Median (95% Confidence Interval) [ratio]
    -0.002
    -0.009
    -0.02
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Stable ICS-LABA, Reduced ICS/LABA
    Comments Comparison of change in FEV1/FVC ratio
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.14
    Comments
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Stable ICS-LABA, LABA Step Off
    Comments Comparison of change in FEV1/FVC ratio
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Reduced ICS/LABA, LABA Step Off
    Comments Comparison of change in FEV1/FVC ratio
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.031
    Comments
    Method Kruskal-Wallis
    Comments

    Adverse Events

    Time Frame 52 weeks
    Adverse Event Reporting Description Adverse events were assessed via a questionnaire in the clinic visit form, which was completed at every visit. Adverse events were recorded for participants who had newly detected moderate or severe symptoms after baseline.
    Arm/Group Title Stable ICS-LABA Reduced ICS/LABA LABA Step Off
    Arm/Group Description Continuation of Fluticasone/Salmeterol Diskus 250/50 ug twice daily Fluticasone/Salmeterol Diskus: Continuation of Fluticasone/Salmeterol Diskus 250/50 ug twice daily Reduced dose Fluticasone/Salmeterol Diskus 100/50 ug twice daily Fluticasone/Salmeterol Diskus: Reduced dose Fluticasone/Salmeterol Diskus 100/50 ug twice daily Fluticasone Diskus alone 250 ug twice daily without Salmeterol Fluticasone Diskus: Fluticasone Diskus alone 250 ug twice daily without Salmeterol
    All Cause Mortality
    Stable ICS-LABA Reduced ICS/LABA LABA Step Off
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Stable ICS-LABA Reduced ICS/LABA LABA Step Off
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 7/151 (4.6%) 3/149 (2%) 15/155 (9.7%)
    Endocrine disorders
    Elevated blood sugar 0/151 (0%) 0 1/149 (0.7%) 1 1/155 (0.6%) 1
    Graves' Disease, diagnosis 0/151 (0%) 0 0/149 (0%) 0 1/155 (0.6%) 1
    Gastrointestinal disorders
    Partial small bowel obstruction 1/151 (0.7%) 1 0/149 (0%) 0 0/155 (0%) 0
    Abdominal pain 0/151 (0%) 0 0/149 (0%) 0 1/155 (0.6%) 1
    Appendectomy 1/151 (0.7%) 1 0/149 (0%) 0 1/155 (0.6%) 1
    Immune system disorders
    Allergic reaction 1/151 (0.7%) 1 0/149 (0%) 0 1/155 (0.6%) 1
    Injury, poisoning and procedural complications
    Hospitalized for contusion 0/151 (0%) 0 0/149 (0%) 0 1/155 (0.6%) 1
    Musculoskeletal and connective tissue disorders
    Knee replacement (planned) 0/151 (0%) 0 0/149 (0%) 0 2/155 (1.3%) 2
    Renal and urinary disorders
    Acute renal failure, resolved 0/151 (0%) 0 0/149 (0%) 0 1/155 (0.6%) 1
    Reproductive system and breast disorders
    Pregnancy 1/151 (0.7%) 1 2/149 (1.3%) 2 0/155 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Pneumonia 1/151 (0.7%) 1 0/149 (0%) 0 1/155 (0.6%) 1
    Asthma Exacerbation 0/151 (0%) 0 0/149 (0%) 0 5/155 (3.2%) 5
    Chest discomfort, shortness of breath 1/151 (0.7%) 1 0/149 (0%) 0 0/155 (0%) 0
    Vascular disorders
    Hypertension 0/151 (0%) 0 0/149 (0%) 0 1/155 (0.6%) 1
    Stroke 1/151 (0.7%) 1 0/149 (0%) 0 0/155 (0%) 0
    Other (Not Including Serious) Adverse Events
    Stable ICS-LABA Reduced ICS/LABA LABA Step Off
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 110/151 (72.8%) 102/149 (68.5%) 100/155 (64.5%)
    Cardiac disorders
    Increased/irregular heartbeat 6/151 (4%) 6 1/149 (0.7%) 1 6/155 (3.9%) 6
    Gastrointestinal disorders
    Nausea/vomiting 16/151 (10.6%) 17 18/149 (12.1%) 18 12/155 (7.7%) 12
    General disorders
    Headache 38/151 (25.2%) 39 24/149 (16.1%) 29 37/155 (23.9%) 40
    Restlessness or nervousness 17/151 (11.3%) 18 14/149 (9.4%) 15 13/155 (8.4%) 13
    Musculoskeletal and connective tissue disorders
    Musculoskeletal pain 34/151 (22.5%) 36 23/149 (15.4%) 25 26/155 (16.8%) 27
    Respiratory, thoracic and mediastinal disorders
    Upper respiratory infection 45/151 (29.8%) 48 34/149 (22.8%) 35 46/155 (29.7%) 48
    Sore throat 24/151 (15.9%) 28 35/149 (23.5%) 37 34/155 (21.9%) 35
    Hoarseness 26/151 (17.2%) 30 34/149 (22.8%) 34 21/155 (13.5%) 21
    Chest pain 12/151 (7.9%) 12 16/149 (10.7%) 16 18/155 (11.6%) 18
    Cough 53/151 (35.1%) 55 56/149 (37.6%) 59 58/155 (37.4%) 61
    Runny nose/congestion 52/151 (34.4%) 60 48/149 (32.2%) 58 52/155 (33.5%) 55
    Skin and subcutaneous tissue disorders
    Skin bruising 12/151 (7.9%) 12 8/149 (5.4%) 8 9/155 (5.8%) 9

    Limitations/Caveats

    At the time of this release, this data has not undergone peer-review.

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Alexis Rea
    Organization Johns Hopkins University
    Phone 4432878496
    Email area5@jhu.edu
    Responsible Party:
    Robert A. Wise, Professor of Medicine, Johns Hopkins University
    ClinicalTrials.gov Identifier:
    NCT01437995
    Other Study ID Numbers:
    • ADV115922
    First Posted:
    Sep 21, 2011
    Last Update Posted:
    Apr 25, 2017
    Last Verified:
    Mar 1, 2017