Study on Foster Efficacy Maintenance and Reliever vs Foster Maintenance + Salbutamol Reliever in Asthmatics (MART2)

Inclusion Criteria

• Written signed and dated informed consent obtained from patient;
• Male or female patients aged ≥ 18 years;
• Clinical diagnosis of asthma for ≥ 6 months;
• A positive reversibility test, defined as an increase of at least 12% and at least 200 mL from pre-dose in FEV1 30 minutes following 4 puffs (4 × 100 μg) of inhaled salbutamol pMDI. If this could not be achieved, a documented reversibility test to salbutamol within the last 6 months was acceptable for eligibility;
• Patients who experienced at least one severe exacerbation in the 12 months before entry (but not in the last month), defined as deterioration in asthma resulting in hospitalization or emergency room treatment due to asthma worsening, or the need for systemic steroids for at least 3 days because of asthma;
• Using inhaled corticosteroids (ICS) in monotherapy or using ICS in a fixed or free combination with long acting β2 agonists (LABA) at a constant dose (changes in doses for less than seven days were accepted) for two months before V1.
• If patients were under ICS only, the daily dose had to be ≥ non-extrafine 1000 μg BDP or equivalent.
• If patients were under ICS + LABA, the ICS daily dose had to be ≥ non-extrafine 500 μg BDP or equivalent. LABA were to be stopped at least 24 hours before V1.
• Not fully controlled asthmatics (which means partly controlled or/and uncontrolled patients according to GINA guidelines 2007) (apart from asthma exacerbation criteria) in the last month before V1.

Asthma control was assessed in terms of:

• Daytime symptoms (more than twice a week);
• Limitation of activities (any);
• Nocturnal symptoms/awakening (any);
• Need for rescue (more than twice a week);
• Forced expiratory volume in the first second (FEV1) 5 mIU/mL). Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precluded intercourse with a male partner and women whose partners had been sterilized by vasectomy or other means, unless they met the following definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL or were using one or more of the following acceptable methods of contraception:
• Surgical sterilization (e.g. bilateral tubal ligation, hysterectomy);
• Hormonal contraception (implantable, patch, oral);
• Double-barrier methods (any double combination of: IUD, male or female condom, diaphragm, sponge, cervical cap).

Acceptable methods of contraception could include total abstinence at the discretion of the investigator in cases where the age, career, lifestyle, or sexual orientation of the patient ensured compliance. Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods) and withdrawal were not acceptable methods of contraception. Reliable contraception should be maintained throughout the study and for 30 days after study drug discontinuation;

• Body Mass Index (BMI) > 34 kg/m2;
• Patients with lower respiratory tract infections affecting the patient's asthma within 30 days of the screening visit;
• Use of systemic steroids in the last month;
• Patients with other lung diseases such as (but not limited to) COPD, cystic fibrosis, interstitial lung diseases or any other clinically or functionally significant lung disorder;
• Patients who had an uncontrolled respiratory, haematological, immunologic, renal, neurologic, hepatic, endocrinal or other disease, or any condition that could, in the judgment of the investigator, represent for the patients an undue risk or that could compromise the results or interpretation of the study;
• History or current evidence of uncontrolled heart failure, clinically relevant coronary artery disease, recent myocardial infarction, severe hypertension, uncontrolled cardiac arrhythmias;
• Cancer or any other chronic disease with poor prognosis (less than 2 year