Clinical trial NCT01290874: Blacks and Exacerbations on Long Acting Beta Agonists (LABA) vs. Tiotropium (BELT)
Official title: Blacks and Exacerbations on LABA vs. Tiotropium (BELT)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Asthma
Keywords: Asthma
Blacks
LABA
Tiotropium
Spiriva
African American
Serevent
salmeterol
Foradil
formoterol
Advair
Symbicort
Dulera
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: Olmsted Medical Center
name: American Academy of Family Physicians National Research Network
name: Baim Institute for Clinical Research
First posted: 2011-02-07
Enrollment: 1070
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: We are doing this study to learn how genes affect the way that people, specifically Black people, respond to treatment for asthma. Recent studies suggest that people respond differently to some asthma medications (eg Serevent, Foradil). Some people feel better when they use these inhalers, but others may not, and some people get worse. It seems that this difference shows up more often in Blacks than in Whites, which is why we are looking for Black subjects for this study. In all people, this difference seems to depend on their genes or DNA. This study is comparing the use of long acting asthma medications (Serevent, Foradil) to Tiotropium (Spiriva) for the treatment of asthma. Spiriva is used to treat chronic obstructive pulmonary disease (COPD). This study will help to see if this medication is also useful for treating asthma and whether it works better for some people than the current asthma medications.

Detailed description: Asthma is a chronic respiratory disease that affects over 22 million people in the United States. Asthma produces 500,000 hospital admissions and accounts for 10.1 million days of lost work in adults annually. Asthma has been designated a priority condition of the Effective Health Care Program.

Blacks bear a disproportionate burden of asthma morbidity and mortality. In its 2005 report on ethnic disparities in health care, AHRQ identified hospital admissions for asthma as the second largest disparity in quality of health care for Blacks vs. Caucasians.

Long-acting beta-agonists (LABAs) produce extended increases in airway caliber among patients with asthma via action at the beta2-adrenergic receptor (ADRB2). Adding a LABA to an inhaled corticosteroid controller medication (ICS), can decrease asthma symptoms for many individuals and appears to decrease asthma exacerbations. LABA/ICS has become the most commonly prescribed ICS containing medication.

Drugs acting at ADRB2, including LABAs, have been associated with rare loss of long-term asthma control and increased serious adverse outcomes including death and respiratory failure, even when used with ICS. The risk appears four to five-fold greater in Blacks than non-Black patients with asthma.

Consensus guidelines recommend LABAs be added to ICS in those not completely controlled on ICS alone. These recommendations are based on weighing data on the benefit demonstrated in the general population vs. the rare risk of serious adverse outcomes and balancing the apparent benefits vs. the risks of LABAs (Kramer 2009). However, it appears that LABA/ICS may be significantly less effective in Blacks than Caucasians. Comparison of studies with LABA/ICS in Blacks vs. studies where Blacks were a small minority suggests that Blacks may have much less benefit than other racial groups. Additionally, recent data (Wechsler 2009) suggest that a polymorphism at the 16th position of the ADRB2 gene identifies a group of Blacks (those homozygous for arginine (Arg16Arg)) in whom the response of adding a LABA to an ICS is further diminished. This polymorphism is present in \~20% of US Blacks.

Eligibility criteria: Inclusion Criteria:

1. Black (self-identified, with at least one biological parent identified as Black)
2. Male and female subjects, ages 18-75
3. Ability to provide informed consent
4. Clinical history consistent with asthma for \> 1 year.
5. Ability to perform pulmonary function tests
6. FEV1 \> 40% of predicted
7. Receiving inhaled corticosteroids (ICS)/LABA combination therapy, or ICS moderate dose monotherapy and baseline ACQ\>1.25
8. Non-smoker for past year (total lifetime smoking history \< 10 pack-years)

Exclusion Criteria:

1. Use of greater than the equivalent of 1000 mcg inhaled fluticasone daily
2. Chronic use of oral corticosteroids or Anti IgE for asthma
3. Lung disease other than asthma or diagnosis of vocal cord dysfunction.
4. Significant medical illness (other than asthma) that is not stable.
5. Pregnancy or lactation or an unwillingness to maintain effective birth control.
6. History of a significant exacerbation of asthma or respiratory tract infection in the prior 4 weeks
7. History of life-threatening asthma requiring treatment with intubation and mechanical ventilation within 5 years.
8. Hypo sensitization therapy other than an established maintenance regimen.
9. Use of inhaled anticholinergic therapy (ipratropium, tiotropium) in prior month
10. Known contraindication to inhaled tiotropium e.g. narrow angle glaucoma, history of bladder neck obstruction or significant symptoms related to prostatic hypertrophy.
11. Inability to speak and read English.

Primary outcomes:
measure: Time to Asthma Exacerbation (Mean Number of Exacerbations/Person-year)
timeFrame: evaluated monthly (on average) via questionnaire for 12 months
Secondary outcomes:
measure: Change in FEV1
timeFrame: from baseline to 12 months
measure: Change in Asthma Control Questionnaire (ACQ)
timeFrame: from baseline to 12 months
measure: Change in Asthma Quality of Life (AQLQ)
timeFrame: from baseline to 12 months
measure: Change in Asthma Symptom Utility Index (ASUI)
timeFrame: from baseline to 12 months
measure: Change in Symptom-Free Day Questionnaire (SFDQ)
timeFrame: from baseline to 12 months
measure: Change in Rescue Medication Use
timeFrame: from baseline to 12 months
measure: Change in Moderate Asthma Deterioration
timeFrame: from baseline to 12 months
Other outcomes:
Locations:
city: Jacksonville
country: United States
facility: Edward Waters College Medical Center (Mayo)
state: Florida
city: Marietta
country: United States
facility: Urban Family Practice
state: Georgia
city: Newton
country: United States
facility: Albany Area Primary Healthcare, Inc
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: Canton
country: United States
facility: G.A. Carmichael F.H.C.
state: Mississippi
city: Kansas City
country: United States
facility: Swope Parkway Health Center
state: Missouri
city: Bronx
country: United States
facility: Montefiore Medical Group
state: New York
city: Buffalo
country: United States
facility: UNYNET - Jefferson Family Medicine
state: New York
city: Kannapolis
country: United States
facility: Carolinas Medical Center - NorthEast (Lovelace)
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Shaker Heights
country: United States
facility: Family Medicine Occupational Health Center
state: Ohio
city: Ridgeland
country: United States
facility: BJHCHS - Hardeeville Medical Center
state: South Carolina
Study officials:
affiliation: Brigham and Women's Hospital
name: Elliot Israel, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wechsler ME, Yawn BP, Fuhlbrigge AL, Pace WD, Pencina MJ, Doros G, Kazani S, Raby BA, Lanzillotti J, Madison S, Israel E; BELT Investigators. Anticholinergic vs Long-Acting beta-Agonist in Combination With Inhaled Corticosteroids in Black Adults With Asthma: The BELT Randomized Clinical Trial. JAMA. 2015 Oct 27;314(16):1720-30. doi: 10.1001/jama.2015.13277.