Asthma Clinical Research Network (ACRN) Trial - Long-Acting Beta Agonist Response by Genotype (LARGE)

This study has been completed.
Sponsor:
Collaborators:
Asthma Clinical Research Network
Information provided by (Responsible Party):
Vernon M. Chinchilli, PhD, Milton S. Hershey Medical Center
ClinicalTrials.gov Identifier:
NCT00200967
First received: September 12, 2005
Last updated: February 24, 2013
Last verified: February 2013
Results First Received: March 5, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Crossover Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Asthma
Interventions: Drug: salmeterol
Drug: beclomethasone HFA

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Recruitment for the LARGE trial began in November 2004 and the final participant visits occurred in February 2008. Seven academic medical centers throughout the US recruited the participants.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
474 participants were screened: 78 had B16 Arg/Arg genotype; 166 had B16 Gly/Gly genotype; 230 had Arg/Gly genotype. 47 matched Arg/Arg-Gly/Gly pairs entered the 8-week run-in period. 42 Arg/Arg were randomized (2 withdrew, 2 noncompliant, 1 lost); 45 Gly/Gly were randomized (1 withdrew, 1 noncompliant).

Reporting Groups
  Description
B16 Arg/Arg B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA
B16 Gly/Gly B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA

Participant Flow for 4 periods

Period 1:   First Treatment Period
    B16 Arg/Arg     B16 Gly/Gly  
STARTED     42     45  
First Treatment Period     42     45  
COMPLETED     36     44  
NOT COMPLETED     6     1  
Withdrawal by Subject                 5                 1  
Pregnancy                 1                 0  

Period 2:   Wash-out Period
    B16 Arg/Arg     B16 Gly/Gly  
STARTED     36     44  
COMPLETED     36     43  
NOT COMPLETED     0     1  
Lost to Follow-up                 0                 1  

Period 3:   Second Treatment Period
    B16 Arg/Arg     B16 Gly/Gly  
STARTED     36     43  
COMPLETED     35     41  
NOT COMPLETED     1     2  
Withdrawal by Subject                 1                 2  

Period 4:   Run-out Period
    B16 Arg/Arg     B16 Gly/Gly  
STARTED     35     41  
COMPLETED     34     41  
NOT COMPLETED     1     0  
Lost to Follow-up                 1                 0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
B16 Arg/Arg B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA
B16 Gly/Gly B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA
Total Total of all reporting groups

Baseline Measures
    B16 Arg/Arg     B16 Gly/Gly     Total  
Number of Participants  
[units: participants]
  42     45     87  
Age  
[units: participants]
     
<=18 years     0     0     0  
Between 18 and 65 years     42     45     87  
>=65 years     0     0     0  
Age  
[units: years]
Mean ± Standard Deviation
  39  ± 11     42  ± 12     41  ± 12  
Gender  
[units: participants]
     
Female     32     29     61  
Male     10     16     26  
Region of Enrollment  
[units: participants]
     
United States     42     45     87  



  Outcome Measures
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1.  Primary:   Morning (AM) Peak Expiratory Flow (PEF) Rate   [ Time Frame: Measured daily using a hand-held peak flow meter, and then averaged between weeks 0, 2, 6, 10, 14, and 18 of each treatment period ]

2.  Secondary:   Evening (PM) Peak Expiratory Flow (PEF) Rate   [ Time Frame: Measured daily using a hand-held peak flow meter, and then averaged between weeks 0, 2, 6, 10, 14, and 18 of each treatment period ]

3.  Secondary:   Peak Expiratory Flow (PEF) Variability   [ Time Frame: Measured daily using a hand-held peak flow meter, and then averaged between weeks 0, 2, 6, 10, 14, and 18 of each treatment period ]

4.  Secondary:   Asthma Symptoms   [ Time Frame: Recorded daily on a diary card, and then averaged between weeks 0, 2, 6, 10, 14, and 18 of each treatment period ]

5.  Secondary:   Rescue Medication (Ipratropium and Albuterol) Use   [ Time Frame: Recorded daily on a diary card, and then averaged between weeks 0, 2, 6, 10, 14, and 18 of each treatment period ]

6.  Secondary:   Spirometry Forced Expiratory Volume in One Second (FEV1), Pre-bronchodilator   [ Time Frame: Clinic visits at weeks 0, 2, 6, 10, 14, and 18 of each treatment period ]

7.  Secondary:   Spirometry Forced Vital Capacity (FVC), Pre-bronchodilator   [ Time Frame: Clinic visits at weeks 0, 2, 6, 10, 14, and 18 of each treatment period ]

8.  Secondary:   Spirometry Peak Expiratory Flow (PEF) Rate, Pre-bronchodilator   [ Time Frame: Clinic visits at weeks 0, 2, 6, 10, 14, and 18 of each treatment period ]

9.  Secondary:   Exhaled Nitric Oxide (eNO)   [ Time Frame: Clinic visits at weeks 0, 2, 6, 10, 14, and 18 of each treatment period ]

10.  Secondary:   Exhaled Breath Condensate (EBC)   [ Time Frame: Clinic visits at weeks 0, 10, and 18 of each treatment period ]

11.  Secondary:   Methacholine Provocative Concentration 20 (PC20)   [ Time Frame: Clinic visits at weeks 0 and 18 of each treatment period ]

12.  Secondary:   Asthma Control Questionnaire (ACQ)   [ Time Frame: Clinic visits at weeks 0 and 18 of each treatment period ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
The study used a moderately high dose of ICS. Genotype-specific effects may be evident at lower doses of ICS often used in combination therapy. Also, short-acting β2-agonists have been shown to have genotype-specific effects on asthma outcomes.


  More Information
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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.


Results Point of Contact:  
Name/Title: Vernon M. Chinchilli
Organization: Penn State College of Medicine
phone: 717-531-4262
e-mail: vchinchi@psu.edu


Publications of Results:

Responsible Party: Vernon M. Chinchilli, PhD, Milton S. Hershey Medical Center
ClinicalTrials.gov Identifier: NCT00200967     History of Changes
Other Study ID Numbers: 262, 5U10HL074231, U10 HL074073, U10 HL074204, U10 HL074208, U10 HL074212, U10 HL074218, U10 HL074225, U10 HL074227, U10 HL074231
Study First Received: September 12, 2005
Results First Received: March 5, 2009
Last Updated: February 24, 2013
Health Authority: United States: Federal Government