Long-acting Beta Agonist Step Down Study

Study Overview
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Brief Summary
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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
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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.

Official Title
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Long-acting Beta Agonist Step Down Study

Conditions
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Asthma

Intervention / Treatment
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* Drug: Fluticasone/Salmeterol Diskus
* Drug: Fluticasone/Salmeterol Diskus
* Drug: Fluticasone Diskus


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Fluticasone/Salmeterol Diskus 250/50 ug<br>Continuation of Fluticasone/Salmeterol Diskus 250/50 ug twice daily | Drug: Fluticasone/Salmeterol Diskus<br>* Continuation of Fluticasone/Salmeterol Diskus 250/50 ug twice daily<br>* Other names: Salmeterol;|
| Active Comparator: Fluticasone/Salmeterol Diskus 100/50 ug<br>Reduced dose Fluticasone/Salmeterol Diskus 100/50 ug twice daily | Drug: Fluticasone/Salmeterol Diskus<br>* Reduced dose Fluticasone/Salmeterol Diskus 100/50 ug twice daily<br>* Other names: Salmeterol;|
| Active Comparator: Fluticasone Diskus alone 250 ug<br>Fluticasone Diskus alone 250 ug twice daily without Salmeterol | Drug: Fluticasone Diskus<br>* Fluticasone Diskus alone 250 ug twice daily without Salmeterol<br>* Other names: Fluticasone;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, Step down therapy, Inhaled corticosteroids, Long-acting beta agonists, Fluticasone Salmeterol