Long-acting Beta Agonist Step Down Study

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.

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 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 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 CHF, unstable angina, recent MI, 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