Evaluating Long Acting Beta Agonists Used to Treat Asthma Among Those With Either Arg/Arg or Gly/Gly Genotypes

Arg/Arg Genotype and Long Acting Beta Agonists in Asthma. Improved Quality of Care for Patients With Asthma.

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00521222

Acronym

ARGARG

Enrollment

Registered

2007-08-27

Start date

2007-06-30

Completion date

2010-11-30

Last updated

2023-04-21

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Asthma

Keywords

asthma, beta agonist, bronchodilator, pulmonary, genotype, pharmacogenomics, corticosteroid, allergy, immunology

Brief summary

The investigators are conducting a study of asthma patients who use fluticasone with salmeterol (Advair) or any other combination of an inhaled corticosteroid (ICS) and a long acting beta agonist (LABA) to manage their asthma symptoms. Participants begin the study by continuing to use fluticasone with salmeterol or substituting fluticasone with salmeterol for their current ICS/LABA medication at their regular dose or the comparable dose(all study medications are provided) for a six-week period. Patients are then separated into 2 groups: one group is asked to use fluticasone (Flovent), the other to use fluticasone with salmeterol , twice daily over a 16-week period (patients will need to be seen monthly during this time). Neither study personnel nor patients will know which drug is being used. Patients are also asked to use a peak flow meter and record their daily results on a form, along with the number of puffs they use of their rescue inhaler each day. They also record any changes in asthma medications and information on any asthma episodes. The investigators hypothesize that there are certain patients with asthma who will do better when a long acting beta agonist is removed from their maintenance asthma medications.

Detailed description

Beta 2 (b2) agonists are the most common type of bronchodilator used to treat asthma. Beta 2 (b2) agonists are agents that bind to b2 receptors and cause muscle relaxation of the airways. There are different variants of the gene (genotypes) that influence how b2 agonists perform among the population. A recent study demonstrated that patients with mild asthma and the Arg/Arg variant at the 16th amino acid position have improved lung function and asthma control when albuterol (Proventil-HFA), a short acting b2 agonist, is replaced with a different class of bronchodilator. The investigators plan to study asthma patients with distinct genetic makeups of the b2 receptor; specifically Arg/Arg and Gly/Gly. Throughout the treatment period, patients will be instructed to use ipratropium bromide (Atrovent-HFA), a bronchodilator which works through a different mechanism for rescue therapy; albuterol will be available for use if necessary. The goal of this study is to determine if the withdrawal of a beta 2 agonist leads to improved asthma control in those asthmatic patients with the Arg/Arg genotype compared with those with the Gly/Gly genotype.

Interventions

DRUGFluticasone with salmeterol

Fluticasone 45mcg, 115mcg, or 230mcg with salmeterol 21mcg, via HFA device, 2 puffs every 12 hrs, over 16 week study period.

DRUGFluticasone HFA

Fluticasone HFA alone at 44mcg, 110mcg or 220 mcg 2 puffs every 12 hrs, over 16 week study period.

DRUGIpratropium HFA

Primary as-needed rescue medication in all treatment groups

DRUGAlbuterol HFA

Secondary as-needed rescue medication in all treatment groups

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Age 18 years or older * History of moderate or severe and persistent asthma * Currently being treated with a long acting beta agonist and inhaled corticosteroid * Forced expiratory volume at one second (FEV1) \> or = 70% at randomization visit (pulmonary function test result) * Women of childbearing potential must be on an effective form of contraception * Ability to read and understand English

Exclusion criteria

* Active smoking or greater than 10-pack-year history of smoking * History of intubation for asthma within the past 10 years * Patients who are pregnant, become pregnant during the study or are breast feeding * Major comorbidity including: severe cardiac disease, uncontrolled hypertension, poorly controlled diabetes, malignancy within the past 5 years (except non-melanoma skin lesions), and pulmonary disease other than asthma

Design outcomes

Primary

Measure	Time frame	Description
Absolute Change in Morning Peak Flow	Up to 16 weeks from baseline	Absolute change in morning peak flow at the end of the 16-week study period compared with baseline (last two weeks of run-in). Peak flow measurement is a test to measure air flowing out of the lung.

Secondary

Measure	Time frame	Description
Change in Forced Expiratory Volume in 1 Second (FEV1) Pre-Bronchodilator	Up to 16 weeks from baseline	Change in Forced Expiratory Volume in 1 Second (FEV1) Pre-Bronchodilator as measured by spirometry
Change in Forced Expiratory Volume in 1 Second (FEV1) Post-Bronchodilator	Up to 16 weeks from baseline	Change in Forced Expiratory Volume in 1 Second (FEV1) Post-Bronchodilator as measured by spirometry
Change in Forced Expiratory Volume in 1 Second (FEV1) Percent Predicted Pre-Bronchodilator	Up to 16 weeks from baseline	Change in Forced Expiratory Volume in 1 Second (FEV1) Percent Predicted Pre-Bronchodilator as measured by spirometry
Change in Asthma Symptom Score	Up to 16 weeks from baseline	Asthma symptom score measures asthma symptoms on a scale from 0 to 3. 0 = No asthma symptoms; 1 = 1-3 asthma episodes each lasting 2 hours or less, all mild; 2= 4 or more asthma episodes that interfered with activity, play, school, or sleep for less than 2 hours; 3= 1 or more asthma episodes lasting longer than 2 hours, or resulting in shortening normal activity, or seeing a doctor, or going to a hospital. A higher score indicates a worse outcome.

Countries

United States

Participant flow

Pre-assignment details

90 participants enrolled (40 Arg/Arg Genotype and 50 Gly/Gly Genotype). Nine Arg/Arg participants and 14 Gly/Gly participants were not randomized due to dropout or ineligibility.

Participants by arm

Arm	Count
Arg/Arg Genotype on Advair (Fluticasone With Salmeterol) HFA Asthma patients with the Arg/Arg genotype who are randomized to continue the combination therapy of a specific long-acting beta 2 agonist (salmeterol) and inhaled corticosteroid (fluticasone) in the form of Advair HFA. Drug: Fluticasone with salmeterol Fluticasone 45mcg, 115mcg, or 230mcg with salmeterol 21mcg, via HFA device, 2 puffs every 12 hrs, over 16 week study period. Other Name: Advair HFA Drug: Ipratropium HFA Primary as-needed rescue medication in all treatment groups Other Name: Atrovent Drug: Albuterol HFA Secondary as-needed rescue medication in all treatment groups	15
Gly/Gly Genotype on Advair (Fluticasone With Salmeterol) HFA Asthma patients with the Gly/Gly genotype who are randomized to continue the combination therapy of a specific long-acting beta 2 agonist (salmeterol) and inhaled corticosteroid (fluticasone) in the form of Advair HFA. Drug: Fluticasone with salmeterol Fluticasone 45mcg, 115mcg, or 230mcg with salmeterol 21mcg, via HFA device, 2 puffs every 12 hrs, over 16 week study period. Other Name: Advair HFA Drug: Ipratropium HFA Primary as-needed rescue medication in all treatment groups Other Name: Atrovent Drug: Albuterol HFA Secondary as-needed rescue medication in all treatment groups	17
Arg/Arg Genotype on Fluticasone HFA Asthma patients with the Arg/Arg genotype who are randomized to fluticasone (Flovent HFA) alone. Drug: Fluticasone HFA Fluticasone HFA alone at 44mcg, 110mcg or 220 mcg 2 puffs every 12 hrs, over 16 week study period. Other Name: Flovent HFA Drug: Ipratropium HFA Primary as-needed rescue medication in all treatment groups Other Name: Atrovent Drug: Albuterol HFA Secondary as-needed rescue medication in all treatment groups	13
Gly/Gly Genotype on Fluticasone HFA Gly/Gly genotype on Fluticasone HFA Drug: Fluticasone HFA Fluticasone HFA alone at 44mcg, 110mcg or 220 mcg 2 puffs every 12 hrs, over 16 week study period. Other Name: Flovent HFA Drug: Ipratropium HFA Primary as-needed rescue medication in all treatment groups Other Name: Atrovent Drug: Albuterol HFA Secondary as-needed rescue medication in all treatment groups	16
Total	61

Withdrawals & dropouts

Period	Reason	FG001	FG002	FG003
Overall Study	Lost to Follow-up	0	1	1
Overall Study	Physician Decision	1	0	1
Overall Study	Withdrawal by Subject	0	2	0

Baseline characteristics

Characteristic	Arg/Arg Genotype on Advair (Fluticasone With Salmeterol) HFA	Gly/Gly Genotype on Advair (Fluticasone With Salmeterol) HFA	Arg/Arg Genotype on Fluticasone HFA	Gly/Gly Genotype on Fluticasone HFA	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	15 Participants	17 Participants	13 Participants	16 Participants	61 Participants
Race/Ethnicity, Customized African-American	5 Participants	6 Participants	3 Participants	4 Participants	18 Participants
Race/Ethnicity, Customized Asian	0 Participants	3 Participants	2 Participants	0 Participants	5 Participants
Race/Ethnicity, Customized Hispanic	1 Participants	3 Participants	3 Participants	2 Participants	9 Participants
Race/Ethnicity, Customized Other	2 Participants	1 Participants	1 Participants	2 Participants	6 Participants
Race/Ethnicity, Customized White	8 Participants	7 Participants	7 Participants	10 Participants	32 Participants
Sex: Female, Male Female	13 Participants	10 Participants	12 Participants	12 Participants	47 Participants
Sex: Female, Male Male	2 Participants	7 Participants	1 Participants	4 Participants	14 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	0 / 15	0 / 17	0 / 13	0 / 16
other Total, other adverse events	3 / 15	3 / 17	3 / 13	3 / 16
serious Total, serious adverse events	0 / 15	0 / 17	0 / 13	0 / 16

Outcome results

Primary

Absolute Change in Morning Peak Flow

Absolute change in morning peak flow at the end of the 16-week study period compared with baseline (last two weeks of run-in). Peak flow measurement is a test to measure air flowing out of the lung.