Asthma Clinical Research Network (ACRN) Trial - Tiotropium Bromide as an Alternative to Increased Inhaled Corticosteroid in Patients Inadequately Controlled on a Lower Dose of Inhaled Corticosteroid (TALC)
Condition: Asthma
MeSH terms: Asthma
Intervention: tiotropium bromide; salmeterol xinafoate; beclomethasone dipropionate
Intervention description: tiotropium bromide inhalation powder 18 mcg once daily; salmeterol xinafoate inhalation powder 50 mcg twice daily; beclomethasone dipropionate 80 mcg twice daily (1xICS) or 160 mcg twice daily (2xICS)
Intervention MeSH terms: Beclomethasone; Bromides; Tiotropium Bromide; Salmeterol Xinafoate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 210.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Typically, people with asthma are initially prescribed a low dose of inhaled corticosteroid
      (ICS) medication to control asthma symptoms. If a low dose of ICS is ineffective at
      controlling symptoms, the addition of a second controller medication is recommended. This
      study will examine the effectiveness of the medication tiotropium bromide combined with a low
      dose of ICS at maintaining asthma control in people with moderately severe asthma.
    

Eligibility criteria:

        Inclusion Criteria for TALC and BASALT Studies:

          -  Clinical history consistent with asthma

          -  Forced expiratory volume in one second (FEV1) greater than 40% of predicted value

          -  Asthma confirmed by one of the following two criteria:

               1. Beta-agonist reversibility to 4 puffs albuterol of at least 12% OR

               2. Methacholine provocative concentration at 20% (PC20) of 8 milligrams per
                  milliliter (mg/mL) or less when not on an inhaled corticosteroid (ICS), or 16
                  mg/mL or less when on an ICS

          -  Need for daily controller therapy (i.e., ICS, leukotriene modifiers, and/or
             long-acting beta-agonists) based on one or more of the following criteria:

               1. Received prescription for or used asthma controller within the 12 months prior to
                  study entry OR

               2. Experienced symptoms for more than twice a week and not on asthma controller

          -  If on inhaled steroids (any drug at any dose not exceeding the equivalent of 1000
             micrograms (mcg) of fluticasone daily), participant must have been on a stable dose
             for at least 2 weeks prior to study entry

          -  Non-smoker (i.e., total lifetime smoking history less than 10 pack-years; no smoking
             for at least 1 year prior to study entry)

          -  Willing to use an effective form of birth control throughout the study

        Inclusion Criteria for TALC Study:

          -  Ability to measure morning (AM) peak expiratory flow (PEF) on schedule using
             electronic peak flow meter (EPFM) and to complete the study diary correctly at least
             75% of the time during the interval between Weeks 2 and 4 of the run-in period

          -  Adherence with study medication dosing at least 75% of the time during the interval
             between Weeks 2 and 4 of the run-in period

          -  No asthma exacerbation requiring use of oral corticosteroids or additional asthma
             medications (including an increased dose of ICS) during the run-in period

          -  FEV1 greater than 40% of the predicted value

        Exclusion Criteria for BASALT and TALC Studies:

          -  Lung disease other than asthma, including chronic obstructive pulmonary disease (COPD)
             and chronic bronchitis

          -  Established or suspected diagnosis of vocal cord dysfunction

          -  Significant medical illness other than asthma

          -  History of respiratory tract infection within the 4 weeks prior to study entry

          -  History of a significant asthma exacerbation within the 4 weeks prior to study entry

          -  History of life-threatening asthma requiring treatment with intubation and mechanical
             ventilation in the 5 years prior to study entry

          -  Hyposensitization therapy other than an established maintenance regimen

          -  Inability to coordinate use of the delivery devices used in the study, based on the
             opinion of the investigator or clinical coordinator

          -  Pregnant

        Exclusion Criteria for TALC Study:

          -  Inability to coordinate use of the medication delivery devices used in the study,
             based on the opinion of the investigator or clinical coordinator

          -  Presence at Week 4 of the run-in period of any of the exclusion criteria stipulated
             for Week 0 of the run-in period (Note: Respiratory tract infections that do not cause
             the participant to meet exacerbation criteria are not considered exclusionary.)