Asthma Clinical Research Network (ACRN)

Salmeterol and Leukotriene Modifiers vs. Salmeterol and ICS Treatment (SLiMSIT

NULL HYPOTHESIS

In patients with moderate persistent asthma, the combination of a long-acting beta-agonist (LABA) and an inhaled corticosteroid (ICS) is not superior to the combination of a LABA and a leukotriene receptor antagonist (LTRA) as judged by treatment failure (a need for intensification of asthma therapy).

DESIGN

SLiMSIT was a 36-week, double-blind, placebo-controlled, crossover study.  Patients who met NAEPP criteria for moderate persistent asthma underwent a 4-week run-in period with a combination of an ICS (beclomethasone HFA 80 mg bid) and an LTRA (montelukast 10 mg once daily). This was followed by a 14-week double-blind treatment period, another 4-week run-in period, and finally a crossing over to a second 14-week double blind treatment period.   The two treatments during the double-blind periods were (1) ICS (beclomethasone HFA 80 mg bid) plus LABA (salmeterol DPI 50 mg bid), and (2) LTRA (montelukast 10 mg once daily) plus LABA (salmeterol DPI 50 mg bid).   The primary outcome variable was time until treatment failure, defined as a significant decrease in FEV1, decrease in PEF, increase in symptoms, increase rescue albuterol use relative to baseline, occurrence of a significant exacerbation, and/or the need for emergency treatment/urgent care.  Secondary outcomes were changes in clinical and physiological outcomes (FEV1, AM and PM PEF, PEF variability, and methacholine PC20), and quality of life scores and rescue albuterol use.

 

RESULTS

Enrollment for SLiMSIT began in September 2002 and the last of 192 patients was randomized in February 2004.  Not all of the patients, however, completed the trial because the ACRN Data and Safety Monitoring Board (DSMB) recommended to the NHLBI on February 20, 2004 that the SLiMSIT trial be terminated prematurely.  The DSMB recommended this action because (1) the stopping rules for the interim data analysis of the primary outcome variable had been met, namely, ICS + LABA demonstrated statistically significant superiority to LTRA + LABA with respect to time to treatment failure, and (2) continuing the trial to full completion in order to provide analyses of secondary outcome variables would not lead to an appreciable gain in knowledge.  Nevertheless, ICS + LABA also demonstrated statistically significant superiority to LTRA + LABA with respect to most of the secondary outcome variables. The major publication is under development