AsthmaPhase 3BELTNCT01290874
Blacks and Exacerbations on Long Acting Beta Agonists (LABA) vs. Tiotropium (BELT)
A Phase 3 study testing Tiotropium, Salmeterol and Formoterol in people with Asthma, run by Brigham and Women's Hospital at 13 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Asthma
- What is being tested?
- Tiotropium, Salmeterol and Formoterol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,070 participants
- Where
- 13 sitesUnited States
- Study dates
- 30 Mar 2011to Jul 2013
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Black (self-identified, with at least one biological parent identified as Black)
- Male and female subjects, ages 18-75
- Ability to provide informed consent
- Clinical history consistent with asthma for > 1 year.
- Ability to perform pulmonary function tests
- FEV1 > 40% of predicted
- Receiving inhaled corticosteroids (ICS)/LABA combination therapy, or ICS moderate dose monotherapy and baseline ACQ>1.25
- Non-smoker for past year (total lifetime smoking history < 10 pack-years)
Who cannot join
- Use of greater than the equivalent of 1000 mcg inhaled fluticasone daily
- Chronic use of oral corticosteroids or Anti IgE for asthma
- Lung disease other than asthma or diagnosis of vocal cord dysfunction.
- Significant medical illness (other than asthma) that is not stable.
- Pregnancy or lactation or an unwillingness to maintain effective birth control.
- History of a significant exacerbation of asthma or respiratory tract infection in the prior 4 weeks
Show all 11Show fewer
- History of life-threatening asthma requiring treatment with intubation and mechanical ventilation within 5 years.
- Hypo sensitization therapy other than an established maintenance regimen.
- Use of inhaled anticholinergic therapy (ipratropium, tiotropium) in prior month
- Known contraindication to inhaled tiotropium e.g. narrow angle glaucoma, history of bladder neck obstruction or significant symptoms related to prostatic hypertrophy.
- Inability to speak and read English.
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
United States13 sites
UNYNET - Jefferson Family Medicine
Buffalo, New York, 14215
G.A. Carmichael F.H.C.
Canton, Mississippi, 39046
Northwestern University
Chicago, Illinois, 60611
Cleveland Clinic
Cleveland, Ohio, 44195
Wayne State University
Detroit, Michigan, 48201
Edward Waters College Medical Center (Mayo)
Jacksonville, Florida, 32209
Carolinas Medical Center - NorthEast (Lovelace)
Kannapolis, North Carolina, 28081
Swope Parkway Health Center
Kansas City, Missouri, 64130
Urban Family Practice
Marietta, Georgia, 30067
Albany Area Primary Healthcare, Inc
Newton, Georgia, 39870
BJHCHS - Hardeeville Medical Center
Ridgeland, South Carolina, 29936
Family Medicine Occupational Health Center
Shaker Heights, Ohio, 44120
Montefiore Medical Group
The Bronx, New York, 10462
About this study
Official title: Blacks and Exacerbations on LABA vs. Tiotropium (BELT)
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.
Read the 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
- Being tested
- Tiotropium, Salmeterol, Formoterol
- Keywords
- Asthma, Blacks, LABA, Tiotropium, Spiriva, African American, Serevent, salmeterol, Foradil, formoterol, Advair, Symbicort, Dulera
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TiotropiumDrug
Also called Spiriva
Tiotropium bromide 18 mcg once daily for one year of treatment.
SalmeterolDrug
Also called Serevent
Salmeterol 50 mcg twice daily for one year of treatment.
FormoterolDrug
Also called Foradil
Formoterol 12 mcg twice daily for one year
| Study group | Role | What they receive |
|---|---|---|
| Tiotropium | Experimental | Tiotropium bromide will be evaluated as a treatment for asthma. Receives: Drug: Tiotropium |
| Salmeterol or Formoterol | Active comparator | Long acting beta agonists (Serevent, Foradil) are the standard treatments for moderate asthma. The efficacy of Tiotropium will be compared to this standard. Receives: Drug: Salmeterol; Drug: Formoterol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Asthma Exacerbation (Mean Number of Exacerbations/Person-year)
We summarize the survival experience using mean number of exacerbations/person-year and compare it using the log-rank test comparing kaplan-meier survival curve.
Measured: evaluated monthly (on average) via questionnaire for 12 months
Secondary outcomes (7)
Change in FEV1
Average change in lung function (FEV1) evaluated by spirometry per participant over 12 months
Measured: from baseline to 12 months
Change in Asthma Control Questionnaire (ACQ)
Average Change in Asthma Control Score Per Participant Over 12 Months Using the Asthma Control Questionnaire (ACQ).
The ACQ has six questions regarding symptoms, rescue short-acting β-agonist use and one about FEV1 % predicted. A 7-point scale (0 = no impairment, 6 = maximum impairment) is used for each question and the ACQ score is the mean value of these questions - hence between 0 (totally controlled) and 6 (severely uncontrolled).
Measured: from baseline to 12 months
Change in Asthma Quality of Life (AQLQ)
Average Change in Asthma Quality of Life Score Per Participant Over 12 Months Using the Asthma Quality of Life Questionnaire (AQLQ).
The AQLQ has 32 questions in four domains (symptoms, activity limitation, emotional function, and environmental stimuli) and measures the functional problems that are troublesome to individuals with asthma. Symptoms (11 items), Activity Limitation (12 items, 5 of which are individualized), Emotional Function (5 items), and Environmental Exposure (4 items); 7-point Likert scale (7 = not impaired at all - 1 = severely impaired); scores range 1-7, with higher scores indicating better quality of life.
Measured: from baseline to 12 months
Change in Asthma Symptom Utility Index (ASUI)
Average Change in Asthma Symptom Utility Score Per Participant Over 12 Months Using the Asthma Symptom Utility Index (ASUI).
The ASUI is an 11-item preference-based outcome measure used in clinical trials and cost-effectiveness studies for asthma and is designed to assess the frequency and severity of cough, wheeze, dyspnea, nighttime awakenings, and side effects, weighted according to patient preferences.
4-point Likert scale to assess frequency (not at all, 1 to 3 days, 4 to 7 days, and 8 to 14 days) and severity (not applicable, mild, moderate and severe); scores range from 0 (worst possible symptoms) to 1 (no symptoms).
Measured: from baseline to 12 months
Change in Symptom-Free Day Questionnaire (SFDQ)
Average Change in Symptom-Free Days Per Participant Over 12 Months Using the Symptom-Free Day Questionnaire (SFDQ).
The asthma symptom free day questionnaire (SFDQ) quantifies the number of days with neither daytime nor nighttime asthma symptoms, nor awakenings due to asthma symptoms.
Measured: from baseline to 12 months
Change in Rescue Medication Use
Average Change in Rescue Medication Use Per Participant Over 12 Months. Monthly questionnaires will evaluate the amount of rescue medication subjects have used on average, measured in puffs per day.
Measured: from baseline to 12 months
Change in Moderate Asthma Deterioration
Average Change in Moderate Asthma Deterioration Per Participant Over 12 Months. The definition of a moderate asthma deterioration should include one or more of the following: deterioration in symptoms, deterioration in lung function, or increased rescue bronchodilator use. These features should last for 2 days or more, but not be severe enough to warrant systemic corticosteroid use and/or hospitalization.
Measured: from baseline to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Feb 2011 (estimated)
- Study start30 Mar 2011
- Primary completionJul 2013
- Study completionJul 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,070 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Olmsted Medical Center, American Academy of Family Physicians National Research Network, Baim Institute for Clinical Research
- Responsible party
- Principal investigator, Elliot Israel, MD, Brigham and Women's Hospital
- Investigators
- Elliot Israel, MD, Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01290874
- Sponsor's protocol ID
- 2010p001898
- Acronym
- BELT
- Status last verified
- Mar 2018
- First submitted
- 28 Dec 2010
- Last updated
- 30 Mar 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
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.
PubMed 26505596Oba 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.
PubMed 36472162
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Blacks and Exacerbations on LABA vs. Tiotropium (BELT)
- ClinicalTrials.gov ID
- NCT01290874
- Acronym / sponsor ID
- BELT / 2010p001898
- Conditions
- Asthma
- Keywords
- Asthma, Blacks, LABA, Tiotropium, Spiriva, African American, Serevent, salmeterol
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,070 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Collaborators
- Olmsted Medical Center, American Academy of Family Physicians National Research Network, Baim Institute for Clinical Research
- Study start
- 30 Mar 2011
- Primary completion
- Jul 2013 (actual)
- Study completion
- Jul 2013 (actual)
- First posted
- 7 Feb 2011 (estimated)
- Results
- Posted 30 Mar 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tiotropium | Experimental | Drug: TiotropiumTiotropium bromide will be evaluated as a treatment for asthma. |
| Salmeterol or Formoterol | Active comparator | Drug: Salmeterol, Drug: FormoterolLong acting beta agonists (Serevent, Foradil) are the standard treatments for moderate asthma. The efficacy of Tiotropium will be compared to this standard. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Black (self-identified, with at least one biological parent identified as Black)
- Male and female subjects, ages 18-75
- Ability to provide informed consent
- Clinical history consistent with asthma for > 1 year.
- Ability to perform pulmonary function tests
Key exclusion criteria (11 listed)
- Use of greater than the equivalent of 1000 mcg inhaled fluticasone daily
- Chronic use of oral corticosteroids or Anti IgE for asthma
- Lung disease other than asthma or diagnosis of vocal cord dysfunction.
- Significant medical illness (other than asthma) that is not stable.
- Pregnancy or lactation or an unwillingness to maintain effective birth control.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TiotropiumAlso: SpirivaTiotropium bromide 18 mcg once daily for one year of treatment. | Drug | Tiotropium |
| SalmeterolAlso: SereventSalmeterol 50 mcg twice daily for one year of treatment. | Drug | Salmeterol or Formoterol |
| FormoterolAlso: ForadilFormoterol 12 mcg twice daily for one year | Drug | Salmeterol or Formoterol |
Primary outcome
Time to Asthma Exacerbation (Mean Number of Exacerbations/Person-year)
Time frame: evaluated monthly (on average) via questionnaire for 12 months
We summarize the survival experience using mean number of exacerbations/person-year and compare it using the log-rank test comparing kaplan-meier survival curve.
7 secondary outcomes
Change in FEV1
Time frame: from baseline to 12 months
Change in Asthma Control Questionnaire (ACQ)
Time frame: from baseline to 12 months
Change in Asthma Quality of Life (AQLQ)
Time frame: from baseline to 12 months
Change in Asthma Symptom Utility Index (ASUI)
Time frame: from baseline to 12 months
Change in Symptom-Free Day Questionnaire (SFDQ)
Time frame: from baseline to 12 months
Change in Rescue Medication Use
Time frame: from baseline to 12 months
Change in Moderate Asthma Deterioration
Time frame: from baseline to 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 26505596Wechsler 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.
- Derived from this study: PubMed 36472162Oba 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.
- Individual participant dataSharing planned: Undecided
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Asthma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elliot Israel, MD principal investigator
Brigham and Women's Hospital
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tiotropium, Salmeterol and Formoterol in people with Asthma, run by Brigham and Women's Hospital at 13 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Mar 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to Asthma Exacerbation (Mean Number of Exacerbations/Person-year) (time frame: evaluated monthly (on average) via questionnaire for 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01290874, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2018.