Asthma Clinical Research Network (ACRN) Trial - Best Adjustment Strategy for Asthma in Long Term (BASALT)

• Sponsor: Milton S. Hershey Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00495157
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Enrollment: 342
• Locations: 10
• Arms: 3
• Duration (Months): 37
• Patients Per Site: 34.2
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

Asthma can be effectively controlled using inhaled corticosteroid medication. Treatment with inhaled corticosteroids often requires periodic adjustments to medication dosing and frequency levels. This study examines whether it is more beneficial to adjust corticosteroid treatment based on asthma symptoms and/or biomarkers of lung function versus standard medical guidelines.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Behavioral: Symptom-based adjustment; Behavioral: Biomarker-based adjustment; Behavioral: Guideline-based adjustment	Phase 3

Detailed Description

Asthma is a common, long-term disease that is caused by inflammation of the airways. Symptoms of asthma may include wheezing, coughing, shortness of breath, and chest tightness. The most common treatment for asthma is the use of inhaled corticosteroid medications with periodic adjustments to treatment intensity. For example, corticosteroid dosage is increased when asthma symptoms worsen and decreased when symptoms improve. However, guidelines for making these adjustments, especially reduced intensity adjustments, have not been well established. In people who are initially well controlled on daily low-dose inhaled corticosteroid therapy, symptom-based adjustment (SBA) and/or biomarker-based adjustment (BBA) of inhaled corticosteroid therapy may be more beneficial at maintaining asthma control than standard, guideline-based adjustments (GBA). The purpose of this study is to determine if adjusting treatment based on symptoms and/or lung function biomarkers is more effective at controlling asthma than adjusting corticosteroid use based on standardized medical guidelines.

This study begins with a 4-week period during which participants are monitored while they use an inhaler containing a low dose of inhaled corticosteroid medication. Participants then are assigned to take part in either the BASALT study or the Tiotropium as an Alternative to Long-Acting Beta-Agonists and Corticosteroids (TALC) study, which is a separate Asthma Clinical Research Network (ACRN) study. Participants in BASALT undergo 2 to 4 weeks of adherence testing, which involves using three inhalers that have electronic monitoring devices attached to them. Participants also are asked to measure and record their breathing rates and lung function in a study diary.

BASALT participants are then randomly assigned to one of three treatment groups: SBA, BBA, or GBA. Each participant is given four inhalers: one inhaler contains albuterol, which is used on an as-needed basis as rescue medication; one inhaler contains corticosteroid medication; and two inhalers contain placebo. One of the latter three inhalers is used each time the albuterol inhaler is used, and the other two inhalers are used on a daily basis. Study visits occur at Weeks 2, 4, 6, 12, 18, 24, 30, and 36 of the treatment period. Inhalers are adjusted during these visits based on SBA, BBA, or GBA guidelines. At selected visits, the following procedures occur: physical exam; blood collection; allergy skin testing; heart rate monitoring; lung function and airway testing; methacholine challenge test to determine asthma severity; and questionnaires to assess asthma control, quality of life, and other healthcare factors. Participants record asthma symptoms, peak flow measurements, and medication usage in a daily diary.

Study Design

• Study Type: Interventional
• Actual Enrollment: 342 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Asthma Clinical Research Network (ACRN) Trial - Best Adjustment Strategy for Asthma in Long Term (BASALT)
• Study Start Date: Jun 1, 2007
• Actual Primary Completion Date: Jul 1, 2010
• Actual Study Completion Date: Jul 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Symptom-based adjustment Symptom-based adjustment of beclomethasone dipropionate administered via a hydrofluoroalkane (HFA) inhaler (QVAR® 40 mcg or QVAR® 80 mcg)	Behavioral: Symptom-based adjustment; Symptom-based adjustment of beclomethasone dipropionate administered via a hydrofluoroalkane (HFA) inhaler (QVAR® 40 mcg or QVAR® 80 mcg)
Experimental: Biomarker-based adjustment Biomarker-based adjustment of beclomethasone dipropionate administered via a hydrofluoroalkane (HFA) inhaler (QVAR® 40 mcg or QVAR® 80 mcg)	Behavioral: Biomarker-based adjustment; Biomarker-based adjustment of beclomethasone dipropionate administered via a hydrofluoroalkane (HFA) inhaler (QVAR® 40 mcg or QVAR® 80 mcg)
Experimental: Guideline-based adjustment Guideline-based adjustment of beclomethasone dipropionate administered via a hydrofluoroalkane (HFA) inhaler (QVAR® 40 mcg or QVAR® 80 mcg)	Behavioral: Guideline-based adjustment; Guideline-based adjustment of beclomethasone dipropionate administered via a hydrofluoroalkane (HFA) inhaler (QVAR® 40 mcg or QVAR® 80 mcg)

Outcome Measures

Primary Outcome Measures

1. Time to Treatment Failure (Measured in Days) [Measured during the 36-week treatment period]

Secondary Outcome Measures

1. Number of Episodes of Treatment Failure [Measured during the 36-week treatment period]

2. Time to First Asthma Exacerbation [Measured during the 36-week treatment period]

3. Number of Asthma Exacerbations [Measured during the 36-week treatment period]

4. Tests of Airway Caliber and Responsiveness (Forced Expiratory Volume in One Second (FEV1) Pre- and Post-bronchodilator Inhalation), Methacholine Provocative Concentration at 20% (PC20) [Measured during the 36-week treatment period]

5. Tests of Airway Inflammation (Exhaled Breath Condensate (EBC), Fractional Exhaled Nitric Oxide (FeNO), Sputum Eosinophils) [Measured during the 36-week treatment period]

6. Quality-of-life (AQLQ), Asthma Control Questionnaire (ACQ), and Number of Visit Days That ACQ is Less Than 1.25 [Measured during the 36-week treatment period]

7. Total Amount of Oral Prednisone Required and Total Amount of Inhaled Steroids [Measured during the 36-week treatment period]

8. Adverse Events [Measured during the 36-week treatment period]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria for BASALT and TALC 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) FEV1 of 8 milligrams per millimeter (mg/mL) or less when not on an inhaled corticosteroid, or 16 mg/mL or less when on an inhaled corticosteroid

• Need for daily controller therapy (i.e., inhaled corticosteroids, 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 BASALT Study:

• Ability to measure peak expiratory flow (PEF) each morning using the electronic peak flow meter (EPFM) device and to accurately transcribe the PEF measurements onto the diary cards at least 75% of the time during the last 2 weeks of the adherence testing period

• 75% compliance with recording peak flow measurements and symptoms in a symptom diary during the last 2 weeks of the adherence testing period

• Ability to take Inhalers A, B, and C at least 75% of scheduled doses; 75% compliance per inhaler is required

• No treatment failure (includes significant asthma exacerbation) within the last 4 weeks

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 exacerbation of asthma 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

Exclusion Criteria for BASALT Study:

• Inability to coordinate use of the medication delivery devices used in the study, based on the opinion of the investigator or clinical coordinator

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, San Diego	San Diego	California	United States	92093
2	University of California, San Francisco	San Francisco	California	United States	94143
3	National Jewish Medical and Research Center	Denver	Colorado	United States	80206
4	Brigham & Women's Hospital	Boston	Massachusetts	United States	02115
5	Washington University, St. Louis	St. Louis	Missouri	United States	63130
6	Columbia University Medical Center	New York	New York	United States	10032
7	Duke University Medical Center	Durham	North Carolina	United States	27710
8	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
9	University of Texas Medical Branch	Galveston	Texas	United States	77555
10	University of Wisconsin, Madison	Madison	Wisconsin	United States	53706

Sponsors and Collaborators

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

Investigators

• Principal Investigator: William J. Calhoun, MD, University of Texas, Galveston
• Principal Investigator: Mario Castro, MD, Washington University School of Medicine
• Principal Investigator: Robert F. Lemanske, MD, University of Wisconsin, Madison
• Principal Investigator: Richard J. Martin, MD, National Jewish Health
• Principal Investigator: Elliot Israel, MD, Brigham and Women's Hospital
• Principal Investigator: Stephen P. Peters, MD, PhD, Wake Forest University Health Sciences
• Principal Investigator: Homer A. Boushey, MD, University of California, San Francsico
• Principal Investigator: Stephen I. Wasserman, MD, University of California, San Diego
• Principal Investigator: Emily DiMango, MD, Columbia University
• Principal Investigator: Monica Kraft, MD, Duke University
• Study Chair: Reuben M. Cherniack, MD, National Jewish Health

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Click here for the Asthma Clinical Research Network Web site

Publications

None provided.

• Responsible Party: Vernon M. Chinchilli, PhD, Professor and Chair, Department of Public Health Sciences, Milton S. Hershey Medical Center
• ClinicalTrials.gov Identifier: NCT00495157
• Other Study ID Numbers: 494; 5U10HL074231; U10HL074206; U10HL074208; U10HL074073; U10HL074227; U10HL074225; U10HL074204; U10HL074218; U10HL074212; U10HL074231
• First Posted: Jul 2, 2007
• Last Update Posted: Apr 11, 2013
• Last Verified: Apr 1, 2013

• Additional relevant MeSH terms: Asthma

Study Results

Participant Flow

Arm/Group Title	Symptom-based Adjustment	Biomarker-based Adjustment	Guideline-based Adjustment
Arm/Group Description	Symptom-based adjustment of beclomethasone dipropionate administered via a hydrofluoroalkane (HFA) inhaler (QVAR® 40 mcg or QVAR® 80 mcg)	Biomarker-based adjustment of beclomethasone dipropionate administered via a hydrofluoroalkane (HFA) inhaler (QVAR® 40 mcg or QVAR® 80 mcg)	Guideline-based adjustment of beclomethasone dipropionate administered via a hydrofluoroalkane (HFA) inhaler (QVAR® 40 mcg or QVAR® 80 mcg)
Period Title: Overall Study
STARTED	113	115	114
COMPLETED	97	92	101
NOT COMPLETED	16	23	13

Baseline Characteristics

Arm/Group Title	Symptom-based Adjustment	Biomarker-based Adjustment	Guideline-based Adjustment	Total
Arm/Group Description	Symptom-based adjustment of beclomethasone dipropionate administered via a hydrofluoroalkane (HFA) inhaler (QVAR® 40 mcg or QVAR® 80 mcg)	Biomarker-based adjustment of beclomethasone dipropionate administered via a hydrofluoroalkane (HFA) inhaler (QVAR® 40 mcg or QVAR® 80 mcg)	Guideline-based adjustment of beclomethasone dipropionate administered via a hydrofluoroalkane (HFA) inhaler (QVAR® 40 mcg or QVAR® 80 mcg)	Total of all reporting groups
Overall Participants	113	115	114	342
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	111 98.2%	114 99.1%	112 98.2%	337 98.5%
>=65 years	2 1.8%	1 0.9%	2 1.8%	5 1.5%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	36.0 (12.2)	34.8 (11.3)	34.2 (11.9)	35.0 (11.8)
Sex: Female, Male (Count of Participants)
Female	83 73.5%	82 71.3%	72 63.2%	237 69.3%
Male	30 26.5%	33 28.7%	42 36.8%	105 30.7%
Region of Enrollment (participants) [Number]
United States	113 100%	115 100%	114 100%	342 100%

Outcome Measures

1. Primary Outcome

Title	Time to Treatment Failure (Measured in Days)
Time Frame	Measured during the 36-week treatment period

Outcome Measure Data

Analysis Population Description

All participants were followed for time to treatment failure or right censoring (measured in days).

Arm/Group Title	Symptom-based Adjustment	Biomarker-based Adjustment	Guideline-based Adjustment
Arm/Group Description	Symptom-based adjustment of beclomethasone dipropionate administered via a hydrofluoroalkane (HFA) inhaler (QVAR® 40 mcg or QVAR® 80 mcg)	Biomarker-based adjustment of beclomethasone dipropionate administered via a hydrofluoroalkane (HFA) inhaler (QVAR® 40 mcg or QVAR® 80 mcg)	Guideline-based adjustment of beclomethasone dipropionate administered via a hydrofluoroalkane (HFA) inhaler (QVAR® 40 mcg or QVAR® 80 mcg)
Measure Participants	113	115	114
Mean (Standard Error) [days]	196.9 (4.0)	225.2 (5.6)	182.3 (4.7)

2. Secondary Outcome

Title	Number of Episodes of Treatment Failure
Time Frame	Measured during the 36-week treatment period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Time to First Asthma Exacerbation
Time Frame	Measured during the 36-week treatment period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Number of Asthma Exacerbations
Time Frame	Measured during the 36-week treatment period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Tests of Airway Caliber and Responsiveness (Forced Expiratory Volume in One Second (FEV1) Pre- and Post-bronchodilator Inhalation), Methacholine Provocative Concentration at 20% (PC20)
Time Frame	Measured during the 36-week treatment period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Tests of Airway Inflammation (Exhaled Breath Condensate (EBC), Fractional Exhaled Nitric Oxide (FeNO), Sputum Eosinophils)
Time Frame	Measured during the 36-week treatment period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Quality-of-life (AQLQ), Asthma Control Questionnaire (ACQ), and Number of Visit Days That ACQ is Less Than 1.25
Time Frame	Measured during the 36-week treatment period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Secondary Outcome

Title	Total Amount of Oral Prednisone Required and Total Amount of Inhaled Steroids
Time Frame	Measured during the 36-week treatment period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

9. Secondary Outcome

Title	Adverse Events
Time Frame	Measured during the 36-week treatment period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	Symptom-based Adjustment		Biomarker-based Adjustment		Guideline-based Adjustment
Arm/Group Description	Symptom-based adjustment of beclomethasone dipropionate administered via a hydrofluoroalkane (HFA) inhaler (QVAR® 40 mcg or QVAR® 80 mcg)		Biomarker-based adjustment of beclomethasone dipropionate administered via a hydrofluoroalkane (HFA) inhaler (QVAR® 40 mcg or QVAR® 80 mcg)		Guideline-based adjustment of beclomethasone dipropionate administered via a hydrofluoroalkane (HFA) inhaler (QVAR® 40 mcg or QVAR® 80 mcg)
All Cause Mortality
	Symptom-based Adjustment		Biomarker-based Adjustment		Guideline-based Adjustment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Symptom-based Adjustment		Biomarker-based Adjustment		Guideline-based Adjustment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/113 (5.3%)		0/115 (0%)		1/114 (0.9%)
General disorders
hospitalizations for unrelated events	6/113 (5.3%)	6	0/115 (0%)	0	1/114 (0.9%)	1
Other (Not Including Serious) Adverse Events
	Symptom-based Adjustment		Biomarker-based Adjustment		Guideline-based Adjustment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/113 (1.8%)		7/115 (6.1%)		8/114 (7%)
Respiratory, thoracic and mediastinal disorders
urgent care for asthma	2/113 (1.8%)	2	7/115 (6.1%)	7	8/114 (7%)	8

Limitations/Caveats

[Not Specified]

More Information

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.