Date: 2016-03-06
Type of information: Publication of results in a medical journal
phase: 4
Announcement: publication of results in The New English Journal of Medicine
Company: GSK (UK)
Product: Advair® Diskus® (salmeterol and fluticasone propionate)
Action
mechanism: long-acting beta2-agonist (LABA)/ corticosteroid. Advair® Diskus® is a combination of the LABA, salmeterol, and inhaled corticosteroid (ICS), fluticasone propionate (FP).
Disease: asthma
Therapeutic area: Allergic diseases - Inflammatory diseases - Respiratory diseases
Country: Argentina, Australia, Austria, Belgium, Bulgaria, Canada, Chile, Colombia, Croatia, Czech Republic, Denmark, Germany, Hungary, Indonesia, Italy, Republic of Korea, Latvia, Lithuania, Malaysia, Mexico, Peru, Philippines, Poland, Romania, Russian Federation, Serbia, Slovakia, South Africa, Spain, Taiwan, Ukraine, UK, USA
Trial
details: SAS115359 is a safety and efficacy study of inhaled fluticasone propionate/salmeterol combination versus inhaled fluticasone propionate in the treatment of adolescent and adult subjects with asthma. The purpose of this study is to assess whether the risk of serious asthma-related events (asthma-related hospitalizations, endotracheal intubations, and deaths) in adolescents and adults (12 years of age and older) taking inhaled fluticasone propionate/salmeterol combination is the same as those taking inhaled fluticasone propionate alone. (NCT01475721 )
Latest
news: * On March 6, 2016, GSK announced publication of results from the ‘LABA’ (long acting beta2-agonist) safety study, AUSTRI (SAS115359) in the New England Journal of Medicine (NEJM). The study, which reported results in October, compared Advair® Diskus®, a combination of the LABA, salmeterol, and inhaled corticosteroid (ICS), fluticasone propionate (FP), to FP monotherapy, to assess the safety profiles of each medicine when used to treat adolescent and adult patients with asthma. This was assessed by the composite endpoint of serious asthma-related events (deaths, intubations or hospitalisations) and showed that Advair had a safety profile comparable to FP, including no asthma-related deaths in either arm. These results are being simultaneously presented at the American Academy of Asthma, Allergy and Immunology (AAAAI) Congress in Los Angeles, California. AUSTRI was undertaken as a post-marketing requirement of GSK for the FDA. Three other manufacturers of LABA-containing products, which are also indicated for the treatment of asthma, are undertaking identical studies designed to evaluate whether the addition of a LABA to an ICS increased the risk of an event in the composite endpoint of serious asthma-related events in adolescents and adults with asthma. AUSTRI is the first of the large-scale safety studies to report results and was conducted in over 11,000 patients. Patients were required to have a history of asthma for at least one year prior to randomisation and experienced a severe asthma exacerbation requiring treatment with oral corticosteroids (or their equivalent) or an asthma-related hospitalisation in the year prior to treatment, but not in the 30 days prior to randomisation. Patients were randomised to either fluticasone propionate/salmeterol combination (FSC) or FP. The FP (ICS) treatment dose (100mcg bd, 250mcg bd, 500mcg bd) was determined by the previous use of controller medications and an assessment of the patient’s asthma control. Upon entry into the study, patients took part in a screening period of up to two weeks, a randomisation visit (visit 2) followed by a treatment period of 26 weeks where patients attended 3 on-treatment clinic visits. In months where there was not a visit, patients were contacted by telephone. Serious adverse events were collected within six months after the first use of study drug or seven days after the last date of study drug treatment, whichever date was greater. Patients were permitted to use albuterol/salbutamol rescue medication throughout the study. The primary analysis was to determine whether the addition of LABA to ICS therapy (FSC) is non-inferior to ICS therapy alone (FP) on risk of a composite of serious asthma events (asthma-related hospitalisation, intubation and death). To demonstrate non-inferiority, a predefined margin of 2 was required, meaning the upper limit of the 95% confidence interval needed to be less than two to rule out a doubling in the risk of incidence on FSC compared with FP. All serious asthma related events were adjudicated by an independent committee. In addition to the AUSTRI study, GSK is also conducting a second LABA safety study, VESTRI, in children with asthma aged 4 – 11 years of age. This study is on track to report at the end of Q1 2016.
