BARD: Best African American Response to Asthma Drugs

• Sponsor: Milton S. Hershey Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01967173
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Enrollment: 574
• Locations: 28
• Arms: 8
• Duration (Months): 40.9
• Patients Per Site: 20.5
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The purpose of this study is to find the best asthma treatment to add for Blacks who have asthma that is not well controlled on a low dose of inhaled steroid. This study will also try to find out if Black adults and children differ in how they respond to the medications used in this study.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: Flovent Diskus® 100 mcg; Drug: Flovent Diskus® 250 mcg; Drug: Flovent Diskus® 500 mcg; Drug: Advair Diskus® 100/50 mcg; Drug: Advair Diskus® 250/50 mcg	Phase 3

Detailed Description

BARD is a 66 week prospective, randomized, double-blind, crossover trial in Blacks (individuals who self-report Black ancestry) who have inadequately controlled asthma while taking low-dose inhaled corticosteroids (ICS). BARD will examine the efficacy of increasing the dose of ICS with or without the addition of a long-acting beta agonist (LABA) to determine whether individual patients respond better to one treatment than another and, if so, whether the responses are different for children and adults or if they are related to genetic ancestry.

Study Design

• Study Type: Interventional
• Actual Enrollment: 574 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Best African American Response to Asthma Drugs
• Study Start Date: Feb 1, 2014
• Actual Primary Completion Date: Jul 1, 2017
• Actual Study Completion Date: Jul 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Crossover sequence 1 Flovent Diskus® 250 mcg,followed by Advair Diskus® 250/50 mcg, followed by Flovent Diskus® 100 mcg, followed by Advair Diskus® 100/50 mcg	Drug: Flovent Diskus® 100 mcg; Flovent is an ICS; Drug: Flovent Diskus® 250 mcg; Flovent is an ICS; Drug: Advair Diskus® 100/50 mcg; Advair is an ICS/LABA combination; Drug: Advair Diskus® 250/50 mcg; Advair is an ICS/LABA combination
Experimental: Crossover sequence 2 Advair Diskus® 250/50 mcg, followed by Advair Diskus® 100/50 mcg, followed by Flovent Diskus® 250 mcg, followed by Flovent Diskus® 100 mcg	Drug: Flovent Diskus® 100 mcg; Flovent is an ICS; Drug: Flovent Diskus® 250 mcg; Flovent is an ICS; Drug: Advair Diskus® 100/50 mcg; Advair is an ICS/LABA combination; Drug: Advair Diskus® 250/50 mcg; Advair is an ICS/LABA combination
Experimental: Crossover sequence 3 Flovent Diskus® 100 mcg, followed by Flovent Diskus® 250 mcg, followed by Advair Diskus® 100/50 mcg, followed by Advair Diskus® 250/50 mcg	Drug: Flovent Diskus® 100 mcg; Flovent is an ICS; Drug: Flovent Diskus® 250 mcg; Flovent is an ICS; Drug: Advair Diskus® 100/50 mcg; Advair is an ICS/LABA combination; Drug: Advair Diskus® 250/50 mcg; Advair is an ICS/LABA combination
Experimental: Crossover sequence 4 Advair Diskus® 100/50 mcg, followed by Flovent Diskus® 100 mcg, followed by Advair Diskus® 250/50 mcg, followed by Flovent Diskus® 250 mcg	Drug: Flovent Diskus® 100 mcg; Flovent is an ICS; Drug: Flovent Diskus® 250 mcg; Flovent is an ICS; Drug: Advair Diskus® 100/50 mcg; Advair is an ICS/LABA combination; Drug: Advair Diskus® 250/50 mcg; Advair is an ICS/LABA combination
Experimental: Crossover sequence 5 Flovent Diskus® 500 mcg, followed by Advair Diskus® 250/50 mcg, followed by Flovent Diskus® 250 mcg, followed by Advair Diskus® 100/50 mcg	Drug: Flovent Diskus® 250 mcg; Flovent is an ICS; Drug: Flovent Diskus® 500 mcg; Flovent is an ICS; Drug: Advair Diskus® 100/50 mcg; Advair is an ICS/LABA combination; Drug: Advair Diskus® 250/50 mcg; Advair is an ICS/LABA combination
Experimental: Crossover sequence 6 Advair Diskus® 250/50 mcg, followed by Advair Diskus® 100/50 mcg, followed by Flovent Diskus® 500 mcg, followed by Flovent Diskus® 250 mcg	Drug: Flovent Diskus® 250 mcg; Flovent is an ICS; Drug: Flovent Diskus® 500 mcg; Flovent is an ICS; Drug: Advair Diskus® 100/50 mcg; Advair is an ICS/LABA combination; Drug: Advair Diskus® 250/50 mcg; Advair is an ICS/LABA combination
Experimental: Crossover sequence 7 Flovent Diskus® 250 mcg, followed by Flovent Diskus® 500 mcg, followed by Advair Diskus® 100/50 mcg, followed by Advair Diskus® 250/50 mcg	Drug: Flovent Diskus® 250 mcg; Flovent is an ICS; Drug: Flovent Diskus® 500 mcg; Flovent is an ICS; Drug: Advair Diskus® 100/50 mcg; Advair is an ICS/LABA combination; Drug: Advair Diskus® 250/50 mcg; Advair is an ICS/LABA combination
Experimental: Crossover sequence 8 Advair Diskus® 100/50 mcg, followed by Flovent Diskus® 250 mcg, followed by Advair Diskus® 250/50 mcg, followed by Flovent Diskus® 500 mcg	Drug: Flovent Diskus® 250 mcg; Flovent is an ICS; Drug: Flovent Diskus® 500 mcg; Flovent is an ICS; Drug: Advair Diskus® 100/50 mcg; Advair is an ICS/LABA combination; Drug: Advair Diskus® 250/50 mcg; Advair is an ICS/LABA combination

Outcome Measures

Primary Outcome Measures

1. The Primary Outcome is a Composite Measure That Uses Exacerbations, Asthma Control Days During the Last 12 of 14 Weeks of a Treatment Regimen, and Percent Predicted FEV1 at the End of a Treatment Regimen. [The last 12 weeks of each 14-week treatment period]

   This composite outcome uses a hierarchical method to ascertain differences in asthma control. For each participant, treatments are first compared to see if they differ in terms of exacerbations. If one treatment results in fewer exacerbations than another, it is deemed the superior treatment and no further comparisons are made. If treatment superiority cannot be assigned by exacerbations, then they are compared by asthma control days (ACDs). If one treatment yields at least 31 annualized ACDs more than another, it is deemed the superior treatment. If treatment superiority still cannot be assigned by ACDs, then they are compared by percent predicted FEV1 at the end of a treatment period. If one treatment yields at least 5% greater FEV1 than another, it is deemed the superior treatment. If treatment superiority cannot be assigned by exacerbations, ACDs or FEV1, then that participant is classified as having no differential response.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 5 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Individuals who self-report Black ancestry (with at least 1 Black grandparent).

2. Able to perform reproducible spirometry according to ATS criteria.

3. Clinical history consistent with asthma.

4. Baseline FEV1≥40% of predicted and/or post-bronchodilator FEV1≥40% of predicted.

5. Asthma confirmed either by: (1) Beta-agonist reversibility to 4 puffs albuterol ≥ 12% OR (2) PC20FEV1 ≤ 16 mg/ml OR (3) an absolute relative change in %predicted FEV1 of ≥ 12% over two measurements documented by repeat spirogram over the previous year

6. Either: A) inadequately controlled on low-, medium- or high-dose ICS monotherapy, or low- or medium-dose ICS/LABA, or B) well-controlled on medium- or high-dose ICS monotherapy, or low-, medium- or high-dose ICS/LABA. Inadequate asthma control will be defined as an ACT/c-ACT score <20; well-controlled asthma will be defined as an ACT/c-ACT score ≥20.

7. Stable asthma controller therapy dose (ICS or ICS/LABA) for the 2 weeks prior to enrollment.

8. Non-smoker (total lifetime smoking history < 5 pack-years if <18, or <10 pack-years if ≥18 years of age; no smoking for at least 1 year).

9. For participants ≥18 years of age: Ability to provide informed consent. For participants under 18 years of age: Ability to provide verbal or written assent and ability of parent to provide informed consent.

Exclusion Criteria:

1. Medical contraindication to LABA or history of adverse reactions to ICS or LABA preparations or any of their ingredients.

2. Current or prior use of medications known to significantly interact with corticosteroid disposition within the two-week period preceding enrollment.

3. Unwilling to provide a blood sample for DNA extraction and genetic analysis.

4. Major medical problems prohibiting study participation, i.e. presence of chronic or active lung disease other than asthma or history of unstable significant medical illness other than asthma, including thyroid disease, diabetes mellitus, Cushing's disease, Addison's disease, hepatic disease, or concurrent medical problems that could require oral corticosteroids during the study or that would place the participant at increased risk.

5. Systemic corticosteroid treatment for any condition within 4 weeks of enrollment or more than five courses of systemic corticosteroids in the past year.

6. History of a life-threatening asthma exacerbation requiring intubation, mechanical ventilation, or resulting in a hypoxic seizure within the last 2 years.

7. History of a respiratory tract infection within 4 weeks of enrollment.

8. If a female of child-bearing potential, failure to practice abstinence or use an acceptable birth control method.

9. Pregnancy or lactation or planning to get pregnant during the course of the trial.

10. Receiving hyposensitization therapy other than an established maintenance regimen defined as a continuous regimen for ≥ 3 months prior to enrollment.

11. Participation in an intervention trial or use of investigative drugs in the past 30 days or plans to enroll in such a trial during the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Arizona College of Medicine	Tucson	Arizona	United States	85724
2	Children's Hospital & Research Center Oakland	Oakland	California	United States	94609
3	UCSF Benioff Children's Hospital	San Francisco	California	United States	94143
4	University of California - San Francisco	San Francisco	California	United States	94143
5	National Jewish Health	Denver	Colorado	United States	80206
6	Nemours Children's Clinic	Jacksonville	Florida	United States	32207
7	Nemours Children's Clinic	Orlando	Florida	United States	32827
8	Emory University	Atlanta	Georgia	United States	30322
9	Northwestern Memorial Hospital	Chicago	Illinois	United States	60611
10	Rush University Medical Center	Chicago	Illinois	United States	60612
11	University of Illinois at Chicago	Chicago	Illinois	United States	60612
12	Ann and Robert H. Lurie Children's Hospital	Chicago	Illinois	United States	60614
13	University of Chicago	Chicago	Illinois	United States	60637
14	Brigham & Women's Hospital	Boston	Massachusetts	United States	02115
15	Children's Hospital Boston	Boston	Massachusetts	United States	02115
16	St. Louis Children's Hospital	Saint Louis	Missouri	United States	63110
17	Washington University	Saint Louis	Missouri	United States	63110
18	University of New Mexico	Albuquerque	New Mexico	United States	87131
19	Columbia University Medical Center	New York	New York	United States	10032
20	Duke University School of Medicine	Durham	North Carolina	United States	27110
21	North Carolina Clinical Research	Raleigh	North Carolina	United States	27607
22	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
23	Rainbow Babies and Children's Hospital, Case Western Reserve University	Cleveland	Ohio	United States	44106
24	Allegheny General Hospital	Pittsburgh	Pennsylvania	United States	15212
25	University of Pittsburgh	Pittsburgh	Pennsylvania	United States	15213
26	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania	United States	15224
27	University of Wisconsin-Madison	Madison	Wisconsin	United States	53792
28	Center for Urban Population Health	Milwaukee	Wisconsin	United States	53223

Sponsors and Collaborators

• Milton S. Hershey Medical Center
• National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Study Chair: William Busse, MD, University of Wisconsin, Madison

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 21, 2017

More Information

Additional Information:

• AsthmaNet

Publications

None provided.

• Responsible Party: dave mauger, Principal Investigator, AsthmaNet Data Coordinating Center, Milton S. Hershey Medical Center
• ClinicalTrials.gov Identifier: NCT01967173
• Other Study ID Numbers: AsthmaNet 006; 1U10HL098115
• First Posted: Oct 22, 2013
• Last Update Posted: Nov 15, 2018
• Last Verified: Oct 1, 2018

• Keywords provided by dave mauger, Principal Investigator, AsthmaNet Data Coordinating Center, Milton S. Hershey Medical Center: Asthma; Fluticasone; Salmeterol
• Additional relevant MeSH terms: Asthma; Fluticasone; Xhance; Fluticasone-Salmeterol Drug Combination

Study Results

Participant Flow

Arm/Group Title	Crossover Sequence 1	Crossover Sequence 2	Crossover Sequence 3	Crossover Sequence 4	Crossover Sequence 5	Crossover Sequence 6	Crossover Sequence 7	Crossover Sequence 8
Arm/Group Description	Flovent Diskus® 250 mcg,followed by Advair Diskus® 250/50 mcg, followed by Flovent Diskus® 100 mcg, followed by Advair Diskus® 100/50 mcg Flovent Diskus® 100 mcg: Flovent is an ICS Flovent Diskus® 250 mcg: Flovent is an ICS Advair Diskus® 100/50 mcg: Advair is an ICS/LABA combination Advair Diskus® 250/50 mcg: Advair is an ICS/LABA combination	Advair Diskus® 250/50 mcg, followed by Advair Diskus® 100/50 mcg, followed by Flovent Diskus® 250 mcg, followed by Flovent Diskus® 100 mcg Flovent Diskus® 100 mcg: Flovent is an ICS Flovent Diskus® 250 mcg: Flovent is an ICS Advair Diskus® 100/50 mcg: Advair is an ICS/LABA combination Advair Diskus® 250/50 mcg: Advair is an ICS/LABA combination	Flovent Diskus® 100 mcg, followed by Flovent Diskus® 250 mcg, followed by Advair Diskus® 100/50 mcg, followed by Advair Diskus® 250/50 mcg Flovent Diskus® 100 mcg: Flovent is an ICS Flovent Diskus® 250 mcg: Flovent is an ICS Advair Diskus® 100/50 mcg: Advair is an ICS/LABA combination Advair Diskus® 250/50 mcg: Advair is an ICS/LABA combination	Advair Diskus® 100/50 mcg, followed by Flovent Diskus® 100 mcg, followed by Advair Diskus® 250/50 mcg, followed by Flovent Diskus® 250 mcg Flovent Diskus® 100 mcg: Flovent is an ICS Flovent Diskus® 250 mcg: Flovent is an ICS Advair Diskus® 100/50 mcg: Advair is an ICS/LABA combination Advair Diskus® 250/50 mcg: Advair is an ICS/LABA combination	Flovent Diskus® 500 mcg, followed by Advair Diskus® 250/50 mcg, followed by Flovent Diskus® 250 mcg, followed by Advair Diskus® 100/50 mcg Flovent Diskus® 250 mcg: Flovent is an ICS Flovent Diskus® 500 mcg: Flovent is an ICS Advair Diskus® 100/50 mcg: Advair is an ICS/LABA combination Advair Diskus® 250/50 mcg: Advair is an ICS/LABA combination	Advair Diskus® 250/50 mcg, followed by Advair Diskus® 100/50 mcg, followed by Flovent Diskus® 500 mcg, followed by Flovent Diskus® 250 mcg Flovent Diskus® 250 mcg: Flovent is an ICS Flovent Diskus® 500 mcg: Flovent is an ICS Advair Diskus® 100/50 mcg: Advair is an ICS/LABA combination Advair Diskus® 250/50 mcg: Advair is an ICS/LABA combination	Flovent Diskus® 250 mcg, followed by Flovent Diskus® 500 mcg, followed by Advair Diskus® 100/50 mcg, followed by Advair Diskus® 250/50 mcg Flovent Diskus® 250 mcg: Flovent is an ICS Flovent Diskus® 500 mcg: Flovent is an ICS Advair Diskus® 100/50 mcg: Advair is an ICS/LABA combination Advair Diskus® 250/50 mcg: Advair is an ICS/LABA combination	Advair Diskus® 100/50 mcg, followed by Flovent Diskus® 250 mcg, followed by Advair Diskus® 250/50 mcg, followed by Flovent Diskus® 500 mcg Flovent Diskus® 250 mcg: Flovent is an ICS Flovent Diskus® 500 mcg: Flovent is an ICS Advair Diskus® 100/50 mcg: Advair is an ICS/LABA combination Advair Diskus® 250/50 mcg: Advair is an ICS/LABA combination
Period Title: Overall Study
STARTED	69	69	71	71	73	72	75	74
Completed 1st Period	58	60	67	65	64	62	67	69
Completed 2nd Period	52	58	63	62	63	57	63	61
Completed 3rd Period	48	54	60	61	59	56	59	56
Completed 4th Period	45	52	55	57	56	49	57	50
COMPLETED	45	52	55	57	56	49	57	50
NOT COMPLETED	24	17	16	14	17	23	18	24

Baseline Characteristics

Arm/Group Title	Crossover Sequence 1	Crossover Sequence 2	Crossover Sequence 3	Crossover Sequence 4	Crossover Sequence 5	Crossover Sequence 6	Crossover Sequence 7	Crossover Sequence 8	Total
Arm/Group Description	Flovent Diskus® 250 mcg,followed by Advair Diskus® 250/50 mcg, followed by Flovent Diskus® 100 mcg, followed by Advair Diskus® 100/50 mcg Flovent Diskus® 100 mcg: Flovent is an ICS Flovent Diskus® 250 mcg: Flovent is an ICS Advair Diskus® 100/50 mcg: Advair is an ICS/LABA combination Advair Diskus® 250/50 mcg: Advair is an ICS/LABA combination	Advair Diskus® 250/50 mcg, followed by Advair Diskus® 100/50 mcg, followed by Flovent Diskus® 250 mcg, followed by Flovent Diskus® 100 mcg Flovent Diskus® 100 mcg: Flovent is an ICS Flovent Diskus® 250 mcg: Flovent is an ICS Advair Diskus® 100/50 mcg: Advair is an ICS/LABA combination Advair Diskus® 250/50 mcg: Advair is an ICS/LABA combination	Flovent Diskus® 100 mcg, followed by Flovent Diskus® 250 mcg, followed by Advair Diskus® 100/50 mcg, followed by Advair Diskus® 250/50 mcg Flovent Diskus® 100 mcg: Flovent is an ICS Flovent Diskus® 250 mcg: Flovent is an ICS Advair Diskus® 100/50 mcg: Advair is an ICS/LABA combination Advair Diskus® 250/50 mcg: Advair is an ICS/LABA combination	Advair Diskus® 100/50 mcg, followed by Flovent Diskus® 100 mcg, followed by Advair Diskus® 250/50 mcg, followed by Flovent Diskus® 250 mcg Flovent Diskus® 100 mcg: Flovent is an ICS Flovent Diskus® 250 mcg: Flovent is an ICS Advair Diskus® 100/50 mcg: Advair is an ICS/LABA combination Advair Diskus® 250/50 mcg: Advair is an ICS/LABA combination	Flovent Diskus® 500 mcg, followed by Advair Diskus® 250/50 mcg, followed by Flovent Diskus® 250 mcg, followed by Advair Diskus® 100/50 mcg Flovent Diskus® 250 mcg: Flovent is an ICS Flovent Diskus® 500 mcg: Flovent is an ICS Advair Diskus® 100/50 mcg: Advair is an ICS/LABA combination Advair Diskus® 250/50 mcg: Advair is an ICS/LABA combination	Advair Diskus® 250/50 mcg, followed by Advair Diskus® 100/50 mcg, followed by Flovent Diskus® 500 mcg, followed by Flovent Diskus® 250 mcg Flovent Diskus® 250 mcg: Flovent is an ICS Flovent Diskus® 500 mcg: Flovent is an ICS Advair Diskus® 100/50 mcg: Advair is an ICS/LABA combination Advair Diskus® 250/50 mcg: Advair is an ICS/LABA combination	Flovent Diskus® 250 mcg, followed by Flovent Diskus® 500 mcg, followed by Advair Diskus® 100/50 mcg, followed by Advair Diskus® 250/50 mcg Flovent Diskus® 250 mcg: Flovent is an ICS Flovent Diskus® 500 mcg: Flovent is an ICS Advair Diskus® 100/50 mcg: Advair is an ICS/LABA combination Advair Diskus® 250/50 mcg: Advair is an ICS/LABA combination	Advair Diskus® 100/50 mcg, followed by Flovent Diskus® 250 mcg, followed by Advair Diskus® 250/50 mcg, followed by Flovent Diskus® 500 mcg Flovent Diskus® 250 mcg: Flovent is an ICS Flovent Diskus® 500 mcg: Flovent is an ICS Advair Diskus® 100/50 mcg: Advair is an ICS/LABA combination Advair Diskus® 250/50 mcg: Advair is an ICS/LABA combination	Total of all reporting groups
Overall Participants	69	69	71	71	73	72	75	74	574
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	8.7 (2.0)	8.5 (1.7)	8.4 (1.9)	8.4 (1.8)	38.5 (16.5)	38.5 (15.9)	39.3 (16.0)	35.6 (16.0)	23.2 (18.5)
Sex: Female, Male (Count of Participants)
Female	29 42%	27 39.1%	26 36.6%	28 39.4%	52 71.2%	48 66.7%	47 62.7%	52 70.3%	309 53.8%
Male	40 58%	42 60.9%	45 63.4%	43 60.6%	21 28.8%	24 33.3%	28 37.3%	22 29.7%	265 46.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	7 10.1%	4 5.8%	7 9.9%	6 8.5%	2 2.7%	2 2.8%	2 2.7%	3 4.1%	33 5.7%
Not Hispanic or Latino	62 89.9%	65 94.2%	64 90.1%	65 91.5%	71 97.3%	70 97.2%	73 97.3%	71 95.9%	541 94.3%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
Black	63 91.3%	65 94.2%	68 95.8%	66 93%	69 94.5%	71 98.6%	74 98.7%	73 98.6%	549 95.6%
Other	6 8.7%	4 5.8%	3 4.2%	5 7%	4 5.5%	1 1.4%	1 1.3%	1 1.4%	25 4.4%
Region of Enrollment (participants) [Number]
United States	69 100%	69 100%	71 100%	71 100%	73 100%	72 100%	75 100%	74 100%	574 100%
Forced expiratory volume at one second (FEV1) Percent of Predicted (percent) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percent]	98.1 (15.4)	92.6 (17.9)	95 (13.6)	96.2 (19.1)	83.8 (19.1)	82.9 (15.5)	83.7 (17.3)	83.4 (18)	89.3 (18.1)
Asthma Control Test (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	18.9 (3.8)	18.6 (3.9)	19.2 (3.7)	18.8 (3.8)	18.9 (3.8)
Childhood Asthma Control Test (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	21.5 (3.7)	21.2 (3.6)	20.7 (4.1)	22.1 (3.6)	21.4 (3.8)

Outcome Measures

1. Primary Outcome

Title	The Primary Outcome is a Composite Measure That Uses Exacerbations, Asthma Control Days During the Last 12 of 14 Weeks of a Treatment Regimen, and Percent Predicted FEV1 at the End of a Treatment Regimen.
Description	This composite outcome uses a hierarchical method to ascertain differences in asthma control. For each participant, treatments are first compared to see if they differ in terms of exacerbations. If one treatment results in fewer exacerbations than another, it is deemed the superior treatment and no further comparisons are made. If treatment superiority cannot be assigned by exacerbations, then they are compared by asthma control days (ACDs). If one treatment yields at least 31 annualized ACDs more than another, it is deemed the superior treatment. If treatment superiority still cannot be assigned by ACDs, then they are compared by percent predicted FEV1 at the end of a treatment period. If one treatment yields at least 5% greater FEV1 than another, it is deemed the superior treatment. If treatment superiority cannot be assigned by exacerbations, ACDs or FEV1, then that participant is classified as having no differential response.
Time Frame	The last 12 weeks of each 14-week treatment period

Outcome Measure Data

Analysis Population Description

Not all treatments were used in all participants. Flovent 500 was not used in children and Flovent 100 was not used in adolescents and adults

Arm/Group Title	Adolescents and Adults	Children
Arm/Group Description	All study participant age 12 years or greater	All study participants under age 12 years
Measure Participants	294	280
Advair 100/50 superior to Flovent 250	.49	.46
Advair 100/50 inferior to Flovent 250	.28	.46
Advair 100/50 superior to Flovent 500	.53
Advair 100/50 inferior to Flovent 500	.27
Advair 100/50 superior to Advair 250/50	.42	.47
Advair 100/50 inferior to Advair 250/50	.36	.49
Advair 100/50 superior to Flovent 100	.53
Advair 100/50 inferior to Flovent 100	.41
Advair 250/50 superior to Flovent 250	.46	.43
Advair 250/50 inferior to Flovent 250	.33	.47
Advair 250/50 superior to Flovent 500	.49
Advair 250/50 inferior to Flovent 500	.31
Flovent 500 superior to Flovent 250	.35
Flovent 500 inferior to Flovent 250	.40
Flovent 250 superior to Flovent 100	.51
Flovent 250 inferior to Flovent 100	.37

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Adolescents and Adults
	Comments	Test of the null hypothesis that the superiority of Advair 100/50 compared to Fluticasone 250 is equal to the inferiority of Advair 100/50 compared to Fluticasone 250
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Children
	Comments	Test of the null hypothesis that the superiority of Advair 100/50 compared to Fluticasone 250 is equal to the inferiority of Advair 100/50 compared to Fluticasone 250
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9
	Comments
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Adolescents and Adults
	Comments	Test of the null hypothesis that the superiority of Advair 100/50 compared to Fluticasone 500 is equal to the inferiority of Advair 100/50 compared to Fluticasone 500
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Adolescents and Adults
	Comments	Test of the null hypothesis that the superiority of Advair 100/50 compared to Advair 250/50 is equal to the inferiority of Advair 100/50 compared to Advair 250/50
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.42
	Comments
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Children
	Comments	Test of the null hypothesis that the superiority of Advair 100/50 compared to Advair 250/50 is equal to the inferiority of Advair 100/50 compared to Advair 250/50
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.84
	Comments
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Adolescents and Adults
	Comments	Test of the null hypothesis that the superiority of Advair 250/50 compared to Fluticasone 500 is equal to the inferiority of Advair 250/50 compared to Fluticasone 500
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.015
	Comments
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Adolescents and Adults
	Comments	Test of the null hypothesis that the superiority of Advair 250/50 compared to Fluticasone 250 is equal to the inferiority of Advair 250/50 compared to Fluticasone 250
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.085
	Comments
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Children
	Comments	Test of the null hypothesis that the superiority of Advair 250/50 compared to Fluticasone 250 is equal to the inferiority of Advair 250/50 compared to Fluticasone 250
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.62
	Comments
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Adolescents and Adults
	Comments	Test of the null hypothesis that the superiority of Fluticasone 500 compared to Fluticasone 250 is equal to the inferiority of Fluticasone 500 compared to Fluticasone 250
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.48
	Comments
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Children
	Comments	Test of the null hypothesis that the superiority of Advair 100/50 compared to Fluticasone 100 is equal to the inferiority of Advair 100/50 compared to Fluticasone 100
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.14
	Comments
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Children
	Comments	Test of the null hypothesis that the superiority of Fluticasone 250 compared to Fluticasone 100 is equal to the inferiority of Fluticasone 250 compared to Fluticasone 100
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.096
	Comments
	Method	Mixed Models Analysis
	Comments

Adverse Events

Time Frame	Each participant was followed over the course of four 14-week treatment periods for a total of 56 weeks. The adverse events recorded below are reported at the treatment period level and represent 14 weeks of "at risk" exposure time.
Arm/Group Title	Flovent 250 in Pediatric Group		Advair 250/50 in Pediatric Group		Flovent 100 in Pediatric Group		Advair 100/50 in Pediatric Group		Flovent 500 in Adolescent/Adult Group		Advair 250/50 in Adolescent/Adult Group		Flovent 250 in Adolescent/Adult Group		Advair 100/50 in Adolescent/Adult Group
Arm/Group Description	Flovent 250 in participants under 12 years		Advair 250/50 in participants under 12 years		Flovent 100 in participants under 12 years		Advair 100/50 in participants under 12 years		Flovent 500 in participants 12 years and older		Advair 250/50 in participants 12 years and older		Flovent 250 in participants 12 years and older		Advair 100/50 in participants 12 years and older
All Cause Mortality
	Flovent 250 in Pediatric Group		Advair 250/50 in Pediatric Group		Flovent 100 in Pediatric Group		Advair 100/50 in Pediatric Group		Flovent 500 in Adolescent/Adult Group		Advair 250/50 in Adolescent/Adult Group		Flovent 250 in Adolescent/Adult Group		Advair 100/50 in Adolescent/Adult Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/280 (0%)		0/280 (0%)		0/280 (0%)		0/280 (0%)		0/294 (0%)		0/294 (0%)		0/294 (0%)		0/294 (0%)
Serious Adverse Events
	Flovent 250 in Pediatric Group		Advair 250/50 in Pediatric Group		Flovent 100 in Pediatric Group		Advair 100/50 in Pediatric Group		Flovent 500 in Adolescent/Adult Group		Advair 250/50 in Adolescent/Adult Group		Flovent 250 in Adolescent/Adult Group		Advair 100/50 in Adolescent/Adult Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/280 (2.9%)		1/280 (0.4%)		2/280 (0.7%)		4/280 (1.4%)		10/294 (3.4%)		7/294 (2.4%)		7/294 (2.4%)		8/294 (2.7%)
Blood and lymphatic system disorders
Anemia	0/280 (0%)	0	0/280 (0%)	0	0/280 (0%)	0	0/280 (0%)	0	0/294 (0%)	0	0/294 (0%)	0	1/294 (0.3%)	1	0/294 (0%)	0
Cardiac disorders
Acute Pericarditis	0/280 (0%)	0	0/280 (0%)	0	0/280 (0%)	0	0/280 (0%)	0	0/294 (0%)	0	0/294 (0%)	0	1/294 (0.3%)	1	0/294 (0%)	0
Gastrointestinal disorders
Acute Gastritis	0/280 (0%)	0	0/280 (0%)	0	0/280 (0%)	0	0/280 (0%)	0	1/294 (0.3%)	1	0/294 (0%)	0	0/294 (0%)	0	0/294 (0%)	0
Acute Peptic Ulcer	0/280 (0%)	0	0/280 (0%)	0	0/280 (0%)	0	0/280 (0%)	0	1/294 (0.3%)	1	0/294 (0%)	0	0/294 (0%)	0	0/294 (0%)	0
Chest Pain Not Elsewhere Classified	0/280 (0%)	0	0/280 (0%)	0	0/280 (0%)	0	0/280 (0%)	0	1/294 (0.3%)	1	0/294 (0%)	0	0/294 (0%)	0	0/294 (0%)	0
General disorders
Convulsions Not Elsewhere Classified	1/280 (0.4%)	1	0/280 (0%)	0	0/280 (0%)	0	0/280 (0%)	0	0/294 (0%)	0	0/294 (0%)	0	0/294 (0%)	0	0/294 (0%)	0
Syncope and Collapse	0/280 (0%)	0	0/280 (0%)	0	0/280 (0%)	0	0/280 (0%)	0	0/294 (0%)	0	1/294 (0.3%)	1	0/294 (0%)	0	0/294 (0%)	0
Injury, poisoning and procedural complications
Adverse Food Reaction	0/280 (0%)	0	0/280 (0%)	0	0/280 (0%)	0	0/280 (0%)	0	0/294 (0%)	0	1/294 (0.3%)	1	0/294 (0%)	0	0/294 (0%)	0
Anaphylactic Shock	0/280 (0%)	0	0/280 (0%)	0	0/280 (0%)	0	0/280 (0%)	0	0/294 (0%)	0	1/294 (0.3%)	1	1/294 (0.3%)	1	0/294 (0%)	0
Closed Fracture	0/280 (0%)	0	0/280 (0%)	0	0/280 (0%)	0	1/280 (0.4%)	1	0/294 (0%)	0	0/294 (0%)	0	0/294 (0%)	0	0/294 (0%)	0
Musculoskeletal and connective tissue disorders
Lumbar Spinal Cord Compression	0/280 (0%)	0	0/280 (0%)	0	0/280 (0%)	0	0/280 (0%)	0	1/294 (0.3%)	1	0/294 (0%)	0	0/294 (0%)	0	0/294 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant Neoplasm Brain	0/280 (0%)	0	0/280 (0%)	0	0/280 (0%)	0	0/280 (0%)	0	1/294 (0.3%)	1	0/294 (0%)	0	0/294 (0%)	0	0/294 (0%)	0
Malignant Neoplasm Thyroid	0/280 (0%)	0	0/280 (0%)	0	0/280 (0%)	0	0/280 (0%)	0	0/294 (0%)	0	1/294 (0.3%)	1	0/294 (0%)	0	0/294 (0%)	0
Nervous system disorders
Acute Post-Op Pain	0/280 (0%)	0	0/280 (0%)	0	0/280 (0%)	0	0/280 (0%)	0	0/294 (0%)	0	0/294 (0%)	0	0/294 (0%)	0	1/294 (0.3%)	1
Migraine	0/280 (0%)	0	0/280 (0%)	0	0/280 (0%)	0	0/280 (0%)	0	0/294 (0%)	0	0/294 (0%)	0	0/294 (0%)	0	1/294 (0.3%)	1
Psychiatric disorders
Major Depression	0/280 (0%)	0	0/280 (0%)	0	0/280 (0%)	0	0/280 (0%)	0	0/294 (0%)	0	0/294 (0%)	0	1/294 (0.3%)	1	1/294 (0.3%)	1
Drug Withdrawal	0/280 (0%)	0	0/280 (0%)	0	0/280 (0%)	0	0/280 (0%)	0	0/294 (0%)	0	0/294 (0%)	0	0/294 (0%)	0	1/294 (0.3%)	1
Intermittent Explosive Disorder	0/280 (0%)	0	0/280 (0%)	0	0/280 (0%)	0	1/280 (0.4%)	1	0/294 (0%)	0	0/294 (0%)	0	0/294 (0%)	0	0/294 (0%)	0
Altered Mental Status	0/280 (0%)	0	0/280 (0%)	0	1/280 (0.4%)	1	0/280 (0%)	0	0/294 (0%)	0	0/294 (0%)	0	0/294 (0%)	0	0/294 (0%)	0
Renal and urinary disorders
Acute Kidney Failure	0/280 (0%)	0	0/280 (0%)	0	0/280 (0%)	0	0/280 (0%)	0	0/294 (0%)	0	1/294 (0.3%)	1	0/294 (0%)	0	0/294 (0%)	0
Respiratory, thoracic and mediastinal disorders
Asthma Exacerbation	6/280 (2.1%)	6	1/280 (0.4%)	1	1/280 (0.4%)	1	2/280 (0.7%)	2	4/294 (1.4%)	4	2/294 (0.7%)	2	1/294 (0.3%)	1	3/294 (1%)	3
Pneumonia	0/280 (0%)	0	0/280 (0%)	0	0/280 (0%)	0	0/280 (0%)	0	1/294 (0.3%)	1	0/294 (0%)	0	2/294 (0.7%)	2	0/294 (0%)	0
Flu	1/280 (0.4%)	1	0/280 (0%)	0	0/280 (0%)	0	0/280 (0%)	0	0/294 (0%)	0	0/294 (0%)	0	0/294 (0%)	0	1/294 (0.3%)	1
Other (Not Including Serious) Adverse Events
	Flovent 250 in Pediatric Group		Advair 250/50 in Pediatric Group		Flovent 100 in Pediatric Group		Advair 100/50 in Pediatric Group		Flovent 500 in Adolescent/Adult Group		Advair 250/50 in Adolescent/Adult Group		Flovent 250 in Adolescent/Adult Group		Advair 100/50 in Adolescent/Adult Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	64/280 (22.9%)		52/280 (18.6%)		43/280 (15.4%)		27/280 (9.6%)		53/294 (18%)		47/294 (16%)		35/294 (11.9%)		34/294 (11.6%)
General disorders
Cough	11/280 (3.9%)	20	10/280 (3.6%)	23	13/280 (4.6%)	24	15/280 (5.4%)	21	2/294 (0.7%)	2	3/294 (1%)	5	6/294 (2%)	7	3/294 (1%)	3
Fever	10/280 (3.6%)	11	6/280 (2.1%)	8	16/280 (5.7%)	19	8/280 (2.9%)	10	4/294 (1.4%)	4	3/294 (1%)	3	0/294 (0%)	0	4/294 (1.4%)	5
Respiratory, thoracic and mediastinal disorders
Acute Nasopharyngitis	20/280 (7.1%)	35	18/280 (6.4%)	36	19/280 (6.8%)	33	20/280 (7.1%)	39	24/294 (8.2%)	33	27/294 (9.2%)	46	20/294 (6.8%)	40	22/294 (7.5%)	42
Acute Upper Respiratory Tract Infection	16/280 (5.7%)	25	10/280 (3.6%)	14	11/280 (3.9%)	16	11/280 (3.9%)	20	11/294 (3.7%)	19	11/294 (3.7%)	15	16/294 (5.4%)	24	13/294 (4.4%)	20
Asthma Exacerbation	23/280 (8.2%)	41	20/280 (7.1%)	47	40/280 (14.3%)	54	18/280 (6.4%)	31	18/294 (6.1%)	20	17/294 (5.8%)	20	17/294 (5.8%)	22	18/294 (6.1%)	23

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.