Salmeterol Multi-Center Asthma Research Trial (SMART)
Salmeterol Multi-Center Asthma Research Trial (SMART) Information
DATA FROM A LARGE PLACEBO-CONTROLLED SAFETY STUDY THAT WAS STOPPED EARLY SUGGEST THAT SALMETEROL, A COMPONENT OF ADVAIR DISKUS, MAY BE ASSOCIATED WITH RARE SERIOUS ASTHMA EPISODES OR ASTHMA-RELATED DEATHS. The Salmeterol Multi-center Asthma Research Trial (SMART) enrolled long-acting beta2-agonist-naive patients with asthma to assess the safety ofsalmeterol (Serevent Inhalation Aerosol) 42 mcg twice daily over 28 weeks compared to placebo, when added to usual asthma therapy. The primary endpoint was the combined number of respiratory-related deaths or respiratory-related life-threatening experiences (intubation and mechanical ventilation). Other endpoints included combined asthma-related deaths or life-threatening experiences and asthma-related deaths.
A planned interim analysis was conducted when approximately half of the intended number of patients had been enrolled (N = 26,353). The analysis showed no significant difference for the primary endpoint for the total population. However, a higher number of asthma-related deaths or life-threatening experiences (36 vs. 23) and a higher number of asthma-related deaths (13 vs. 4) occurred in the patients treated with Serevent Inhalation Aerosol. Post hoc subgroup analyses revealed no significant increase in respiratory- or asthma-related episodes, including deaths, in Caucasian patients. In African-Americans, the study showed a small, though statistically significantly greater, number of primary events (20 vs. 7), asthma-related deaths or life-threatening experiences (19 vs. 4), and asthma-related deaths (8 vs. 1) in patients taking Serevent Inhalation Aerosol compared to those taking placebo. Even though SMART did not reach predetermined stopping criteria for the total population, the study was stopped due to the findings in African-American patients and difficulties in enrollment. The data from the SMART study are not adequate to determine whether concurrent use of inhaled corticosteroids, such as fluticasone propionate, a component of Advair Diskus, provides protection from this risk. Therefore, it is not known whether the findings seen with Serevent Inhalation Aerosol would apply to Advair Diskus.
Findings similar to the SMART study findings were reported in a prior 16-week clinical study performed in the United Kingdom, the Salmeterol Nationwide Surveillance (SNS) study. In the SNS study, the incidence of asthma-related death was numerically, though not statistically, greater in patients with asthma treated with salmeterol (42 mcg twice daily) versus albuterol (180 mcg 4 times daily) added to usual asthma therapy.
Given the similar basic mechanisms of action of beta2-agonists, it is possible that the findings seen in the SMART study may be consistent with a class effect.
