Blacks and Exacerbations on Long Acting Beta Agonists (LABA) vs. Tiotropium (BELT)

NCT ID: NCT01290874

Last Updated: 2018-03-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1070 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-03-30
• Study Completion Date: 2013-07-31

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.

Conditions

Asthma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tiotropium

Tiotropium bromide will be evaluated as a treatment for asthma.

Group Type: EXPERIMENTAL

Tiotropium

Intervention Type: DRUG

Tiotropium bromide 18 mcg once daily for one year of treatment.

Salmeterol or Formoterol

Long acting beta agonists (Serevent, Foradil) are the standard treatments for moderate asthma. The efficacy of Tiotropium will be compared to this standard.

Group Type: ACTIVE_COMPARATOR

Salmeterol

Intervention Type: DRUG

Salmeterol 50 mcg twice daily for one year of treatment.

Formoterol

Intervention Type: DRUG

Formoterol 12 mcg twice daily for one year

Interventions

Tiotropium

Tiotropium bromide 18 mcg once daily for one year of treatment.

Intervention Type: DRUG

Salmeterol

Salmeterol 50 mcg twice daily for one year of treatment.

Intervention Type: DRUG

Formoterol

Formoterol 12 mcg twice daily for one year

Intervention Type: DRUG

Other Intervention Names

Spiriva; Serevent; Foradil

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Olmsted Medical Center

OTHER

Sponsor Role: collaborator

American Academy of Family Physicians National Research Network

NETWORK

Sponsor Role: collaborator

Baim Institute for Clinical Research

OTHER

Sponsor Role: collaborator

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Elliot Israel, MD

Director of the Asthma Research Center

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Elliot Israel, MD

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Locations

Edward Waters College Medical Center (Mayo)

Jacksonville, Florida, United States

Urban Family Practice

Marietta, Georgia, United States

Albany Area Primary Healthcare, Inc

Newton, Georgia, United States

Northwestern University

Chicago, Illinois, United States

Wayne State University

Detroit, Michigan, United States

G.A. Carmichael F.H.C.

Canton, Mississippi, United States

Swope Parkway Health Center

Kansas City, Missouri, United States

UNYNET - Jefferson Family Medicine

Buffalo, New York, United States

Montefiore Medical Group

The Bronx, New York, United States

Carolinas Medical Center - NorthEast (Lovelace)

Kannapolis, North Carolina, United States

Cleveland Clinic

Cleveland, Ohio, United States

Family Medicine Occupational Health Center

Shaker Heights, Ohio, United States

BJHCHS - Hardeeville Medical Center

Ridgeland, South Carolina, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 26505596 (View on PubMed)

Oba Y, Anwer S, Maduke T, Patel T, Dias S. Effectiveness and tolerability of dual and triple combination inhaler therapies compared with each other and varying doses of inhaled corticosteroids in adolescents and adults with asthma: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2022 Dec 6;12(12):CD013799. doi: 10.1002/14651858.CD013799.pub2.

Reference Type: DERIVED

PMID: 36472162 (View on PubMed)

Other Identifiers

2010p001898

Identifier Type: -

Identifier Source: org_study_id