Long-acting Beta Agonist Step Down Study (LASST)

Johns Hopkins University

Status and phase: Completed; Phase 4

Conditions: Asthma

Treatments: Drug: Fluticasone Diskus; Drug: Fluticasone/Salmeterol Diskus

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01437995

ADV115922

Details and patient eligibility

About

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.

Full 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.

Enrollment: 459 patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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459 participants in 3 patient groups

Fluticasone/Salmeterol Diskus 250/50 ug

Active Comparator group

Description:

Continuation of Fluticasone/Salmeterol Diskus 250/50 ug twice daily

Treatment:

Drug: Fluticasone/Salmeterol Diskus

Drug: Fluticasone/Salmeterol Diskus

Fluticasone/Salmeterol Diskus 100/50 ug

Active Comparator group

Description:

Reduced dose Fluticasone/Salmeterol Diskus 100/50 ug twice daily

Treatment:

Drug: Fluticasone/Salmeterol Diskus

Drug: Fluticasone/Salmeterol Diskus

Fluticasone Diskus alone 250 ug

Active Comparator group

Description:

Fluticasone Diskus alone 250 ug twice daily without Salmeterol

Treatment:

Drug: Fluticasone Diskus