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)

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00565266

Acronym

TALC

Enrollment

210

Registered

2007-11-29

Start date

2008-05-31

Completion date

2010-05-31

Last updated

2018-07-02

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Asthma

Brief 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.

Detailed description

National and international asthma treatment guidelines recommend ICS as the initial controller therapy for people with asthma who are in need of daily treatment with a controller medication. If treatment with low to moderate doses of ICS is not sufficient to gain and maintain asthma control, current guidelines recommend adding a second controller medication rather than increasing the dose of ICS. Current options for the second medication include a long-acting beta-agonist, a leukotriene modifier, or theophylline. It is possible that other medications, not yet tested, could fill the role of the second controller medication. Tiotropium bromide is a medication that is used to treat chronic obstructive pulmonary disease (COPD). It works by relaxing and opening the air passages to the lungs to make breathing easier. For people with asthma, the addition of tiotropium bromide may be a good option as a second controller medication. The purpose of this study is to determine if combining tiotropium bromide with a low dose of ICS is more effective than doubling the dose of ICS in people with moderately severe asthma. This study will also examine whether the addition of tiotropium bromide to low dose ICS is as effective as the addition of a long-acting beta-agonist at maintaining asthma control. This study will begin with a 4-week run-in period during which participants will be monitored while they use an inhaler containing a low dose of ICS medication. Next, participants will be assigned to take part in either the TALC study or the Best Adjustment Strategy for Asthma in Long Term (BASALT) study, which is a separate Asthma Clinical Research Network (ACRN) study. All TALC participants will then undergo three 16-week treatment periods, which will include the following: * tiotropium bromide inhalation powder 18 mcg once daily (Tio) plus beclomethasone dipropionate 80 mcg twice daily (1xICS) * salmeterol xinafoate inhalation powder 50 mcg twice daily (LABA) plus beclomethasone dipropionate 80 mcg twice daily (1xICS) * beclomethasone dipropionate 160 mcg twice daily (2xICS) The order in which the three treatment periods will occur will be randomly assigned for each participant. Each of the three 16-week treatment periods will consist of 14 weeks of treatment followed by a 2-week washout period, in which participants will receive a single does of ICS. Study visits will occur at baseline and Weeks 2 and 4 of the 4-week run-in period, and at Weeks 4, 9, 14, and 16 of each 16-week treatment period. Spirometry tests to measure lung function will occur at each study visit and exhaled nitric oxide testing and questionnaires to assess asthma control and symptoms will occur at most visits. During study visits at Week 4 of the run-in period and Week 14 of each treatment period, lung function measurements, sputum collection, questionnaires to assess asthma quality-of-life, and measurements of sleep and daytime alertness will all occur. Participants will also record asthma symptoms, peak flow measurements, and medication usage in a daily diary.

Interventions

DRUGtiotropium bromide

tiotropium bromide inhalation powder 18 mcg once daily

DRUGsalmeterol xinafoate

salmeterol xinafoate inhalation powder 50 mcg twice daily

DRUGbeclomethasone dipropionate

beclomethasone dipropionate 80 mcg twice daily (1xICS) or 160 mcg twice daily (2xICS)

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame
Change Between Week 14 and Week 0 in the Morning (AM) Peak Expiratory Flow (PEF)	AM PEF was measured daily during each of the three 14-week treatment periods. The primary analysis constructed the change between week 14 and week 0.

Secondary

Measure	Time frame	Description
Change Between Week 14 and Week 0 in Asthma Symptoms	Asthma symptoms were measured daily during each of the three 14-week treatment periods. The primary analysis constructed the change between week 14 and week 0.	Asthma symptoms were recorded as 0 (absent = no symptom ) 1. (mild = symptom was minimally troublesome, i.e. not sufficient to interfere with normal daily activity or sleep) 2. (moderate = symptom was sufficiently troublesome to interfere with normal daily activity or sleep) 3. (severe = symptom was so severe as to prevent normal activity and/or sleep )
Change Between Week 14 and Week 0 in the Asthma Quality-of-life Questionnaire Score	The asthma quality-of-life questionnaire score was measured on four occasions during each of the three 14-week treatment periods. The primary analysis constructed the change between week 14 and week 0.	Scores on the Asthma Quality-of-Life Questionnaire range from 1 to 7, with a higher score indicating a better quality of life.
Change Between Week 14 and Week 0 in the Forced Expiratory Volume in One Second (FEV1)	FEV1 was measured on four occasions during each of the three 14-week treatment periods. The primary analysis constructed the change between week 14 and week 0.	—
Change Between Week 14 and Week 0 in the Albuterol Rescue Puffs Per Day	Albuterol rescue puffs were measured daily during each of the three 14-week treatment periods. The primary analysis constructed the change between week 14 and week 0.	Total number of puffs from the albuterol (rescue) inhaler during the previous 24 hours (excluding those puffs for preventive use).
Change Between Week 14 and Week 0 in the Proportion of Asthma Control Days	An asthma control day was determined daily during each of the three 14-week treatment periods. The primary analysis constructed the change between week 14 and week 0.	An asthma control day was defined as a day in which there were no symptoms and no albuterol (rescue) puffs.
Change Between Week 14 and Week 0 in the Asthma Control Questionnaire Score	The asthma control questionnaire score was measured on four occasions during each of the three 14-week treatment periods. The primary analysis constructed the change between week 14 and week 0.	Scores on the Asthma Control Questionnaire range from 0 to 6, with a higher score indicating worse asthma control.

Countries

United States

Participant flow

Participants by arm

Arm	Count
All Participants All participants randomized into the six-sequence crossover study	210
Total	210

Baseline characteristics

Characteristic	All Participants
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	3 Participants
Age, Categorical Between 18 and 65 years	207 Participants
Age, Continuous	42.2 years STANDARD_DEVIATION 12.3
Region of Enrollment United States	210 participants
Sex: Female, Male Female	141 Participants
Sex: Female, Male Male	69 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	2 / 203	2 / 196	6 / 195
serious Total, serious adverse events	3 / 203	4 / 196	4 / 195

Outcome results

Primary

Change Between Week 14 and Week 0 in the Morning (AM) Peak Expiratory Flow (PEF)

Time frame: AM PEF was measured daily during each of the three 14-week treatment periods. The primary analysis constructed the change between week 14 and week 0.