Asthma, Bronchial Diseases, Respiratory Tract Infections, Lung Diseases, Obstructive, Lung Diseases, Respiratory Hypersensitivity, Immune System Diseases
Conditions
Keywords
asthma
Brief summary
This is a patient level randomized trial for teenagers and adults with asthma who will be randomized to four arms - enhance usual care, rescue inhaled corticosteroids, azithromycin and both rescue inhaled corticosteroids and azithromycin. Participants in all arms will be offered access to an online asthma symptom monitoring system.
Detailed description
Design. Current activities consist of a Feasibility study to test all activities prior to the full study. The Feasibility study will involve only 5 centers and each participant will be involved for only 3 months. The study will consist of a four arm, patient level randomized trial (N=125). Comparators: Rescue Inhaled Corticosteroids (R-ICS) versus azithromycin versus R-ICS plus azithromycin versus enhanced usual care patients. All arms will include home monitoring of asthma symptoms using various approaches. R-ICS therapy will consist of a corticosteriod/formoterol inhaler, or a stand-alone ICS inhaler used with usual rescue therapy or when available a combination corticosteroid/albuterol inhaler, the initial azithromycin dose will be 500mg (10mg/Kg) three times a week and may be titrated down to 250mg (10mg/Kg) three times per week for side effects. Exacerbations will be blindly adjudicated. Individuals who experience three exacerbations in \< 12 months in the full study will have their treatments stepped-up,unless in the dual treatment arm; control participants going to R-ICS and single therapy participants to dual therapy. In the full study, after a step-up participants will be followed for an additional 12 months. There will be no step-up during the Feasibility phase. Individuals completing either of the azithromycin arms will be offered 6 additional months of follow-up after stopping the azithromycin only.
Interventions
OTHERAsthma Symptom Monitoring online tools
All participants will be provided access to the Asthma Symptom Monitoring tools and 3/4's will be randomized to one of the other three arms above
DRUGInhaled Steroids
participants will use either a combination of budesonide/formoterol or mometasone/formoterol as both controller and rescue therapy or a stand alone inhaled steroid (beclomethasone, budesonide, fluticasone, mometasone, ciclesodine) of their choice with their current reliever therapy or be converted to budesonide/albuterol as rescue therapy
Participants will take 500mg of azithromycin three times a week or 10mg/kg if under 50Kg which may be reduced to 250mg/Kg for side effects
Sponsors
Penn State University
Icahn School of Medicine at Mount Sinai
University of Colorado, Denver
RAND
University of Washington
Rutgers University
University of North Carolina
Brigham and Women's Hospital
Reliant Medical Group
Kelsey Research Foundation
Wake Forest University Health Sciences
DARTNet Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
NONE
Intervention model description
patient randomized trial of three different drug combinations
Eligibility
Sex/Gender
ALL
Age
12 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. A clinical asthma diagnosis for at least 1 year; 2. 12-75 years of age; 3. A current ACT total score of \<20 OR an exacerbation requiring 72 hours or more of parenteral steroids or a hospitalization of at least 24 hours \> 30 days and \< 365 days prior to enrollment; 4. Able to provide consent (adolescents: assent) in English or Spanish; (i.e., cognitively impaired individuals are deemed not to be able to provide consent and thus do not meet inclusion criteria.) 5. Patients with a coexisting clinical diagnosis of COPD are eligible if they meet any one of the following criteria: (i) Never smoker without secondary lung disease causing airway obstruction. (ii) Current or former smoker with obstruction on PFTs, but normal diffusing capacity of the lungs for carbon monoxide (DLCO) in the past 24 months.
Exclusion criteria
1. Life expectancy \<1 year (operationalized by the question to the patient's asthma care clinician Would you be surprised if this person died in the next 12 months? If yes - include, if no - exclude); 2. No ICS prescribed for the individual (does not have to be using the ICS inhaler); 3. Active treatment for hematological or solid organ cancer other than basal cell or skin squamous cell cancer; 4. Allergy to macrolides or conditions for which macrolide administration may possibly be hazardous (e.g., acute or chronic hepatitis, cirrhosis, or other liver disease; end-stage renal disease; uncorrected hypokalemia or hypomagnesemia; clinically significant bradycardia; or history of prolonged cardiac repolarization and QT interval or torsades de pointes); 5. On daily or every other day oral steroids for any reason; 6. Currently on R-ICS or AZ therapy. Individuals on biologics can be enrolled if they have been on a stable dose for \> 6 months and meet the ACT or exacerbation criteria as well as all other criteria. 7. On a medication with known risk (i.e., that is associated with prolonged QT and associated with torsades de pointes even when taken as recommended) or possible risk (i.e., can cause prolonged QT but lacks evidence for risk of torsades de pointes when taken as recommended) - Full lists in Appendix 1. 8. Specified medications for which close monitoring has been recommended in the setting of macrolide administration (digoxin, warfarin, theophylline, ergotamine or dihydroergotamine, cyclosporine, hexobarbital, phenytoin or nelfinavir).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Asthma Control as Measured by the Asthma Control Test (ACT) | Follow up is up to 3 months. | Asthma control represents the degree to which impairment (impact of asthma on patient's daily life) is minimized and the goals of therapy are met. The Asthma Control Test is a participant administered tool for assessing the level of asthma control. Total scores range from 5 to 25, with a score of 20 to 25 indicating well-controlled asthma, a score of 16 to 19 indicating asthma that was not well controlled, and a score of 5 to 15 indicating very poorly controlled asthma. The Asthma Control Test has a score range of 5 to 25 with higher scores indicating better control. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Asthma Quality of Life Questionnaire (AQLQ) as Measured by the Juniper Mini Asthma Quality of Life Questionnaire | Total follow-up period is up to 3 months per participant. | The Asthma Quality of Life Questionnaire is a participant-administered tool for assessing functional impairment. Total scores range from 1 to 7, with a score of 7=no impairment and 1=maximum impairment. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Enhanced Usual Care Participants will be asked to use an online Asthma Symptom Monitoring tool to enhance communication with the medical team as well as self-awareness of their asthma symptoms. There are no study drugs in this arm. All 4 arms of the study will use these tools
Asthma Symptom Monitoring online tools: All participants will be provided access to the Asthma Symptom Monitoring tools and 3/4's will be randomized to one of the other three arms above | 26 |
| Rescue Inhaled Corticosteroids Participants in this arm will either have budesonide/formoterol (Symbicort) or mometasone/formoterol (Dulera), or a stand-alone ICS (beclomethasone/QVAR, or budesonide/Pulmicort, or fluticasone Flovent HFA, Flovent Diskus, ArmonAir RespiClick, Arnuity Ellipta, or mometasone, Asmanex HFA, Asmanex Twisthaler or ciclesodine Alvesco HFA) added to the participants usual treatment or a combination inhaler of corticosteroid and albuterol (AirSupra) that was recently approved
Inhaled Steroids: participants will use either a combination of budesonide/formoterol or mometasone/formoterol as both controller and rescue therapy or a stand alone inhaled steroid (beclomethasone, budesonide, fluticasone, mometasone, ciclesodine) of their choice with their current reliever therapy or be converted to budesonide/albuterol as rescue therapy | 27 |
| Azithromycin Participants will use azithromycin (Zithromax) 500mg three times a week (10mg.kg for participants under 50Kg) which can be dropped to 250 mg three times a week for dose related side effects
Azithromycin Pill: Participants will take 500mg of azithromycin three times a week or 10mg/kg if under 50Kg which may be reduced to 250mg/Kg for side effects | 25 |
| Rescue Inhaled Corticosteroids and Azithromycin This arm includes both the inhaled corticosteroid comparator and the azithromycin comparator as described in those two arms Participants in this arm will either have budesonide/formoterol (Symbicort) or mometasone/formoterol (Dulera), or a stand-alone ICS (beclomethasone/QVAR, or budesonide/Pulmicort, or fluticasone Flovent HFA, Flovent Diskus, ArmonAir RespiClick, Arnuity Ellipta, or mometasone, Asmanex HFA, Asmanex Twisthaler or ciclesodine Alvesco HFA) added to the participants usual treatment or a combination inhaler of corticosteroid and albuterol (AirSupra) that was recently approved AND Participants will use azithromycin (Zithromax) 500mg three times a week (10mg.kg for participants under 50Kg) which can be dropped to 250 mg three times a week for dose related side effects
Inhaled Steroids: participants will use either a combination of budesonide/formoterol or mometasone/formoterol as both controller and rescue therapy or a stand alone inhaled steroid (beclomethasone, budesonide, fluticasone, mometasone, ciclesodine) of their choice with their current reliever therapy or be converted to budesonide/albuterol as rescue therapy
Azithromycin Pill: Participants will take 500mg of azithromycin three times a week or 10mg/kg if under 50Kg which may be reduced to 250mg/Kg for side effects | 25 |
| Total | 103 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 3 | 1 | 1 |
Baseline characteristics
| Characteristic | Rescue Inhaled Corticosteroids | Azithromycin | Enhanced Usual Care | Rescue Inhaled Corticosteroids and Azithromycin | Total |
|---|---|---|---|---|---|
| Age, Continuous | 44.78 years STANDARD_DEVIATION 16.87 | 42.80 years STANDARD_DEVIATION 19.19 | 36.64 years STANDARD_DEVIATION 20.24 | 45.72 years STANDARD_DEVIATION 20.03 | 42.53 years STANDARD_DEVIATION 19.13 |
| Baseline ACT | 17.88 units on a scale STANDARD_DEVIATION 3.98 | 15.64 units on a scale STANDARD_DEVIATION 4.55 | 17.50 units on a scale STANDARD_DEVIATION 4.04 | 14.79 units on a scale STANDARD_DEVIATION 5.08 | 16.50 units on a scale STANDARD_DEVIATION 4.54 |
| Baseline AQLQ | 5.18 units on a scale STANDARD_DEVIATION 1.14 | 4.56 units on a scale STANDARD_DEVIATION 1.21 | 5.28 units on a scale STANDARD_DEVIATION 1.17 | 4.54 units on a scale STANDARD_DEVIATION 1.27 | 4.90 units on a scale STANDARD_DEVIATION 1.23 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 6 Participants | 8 Participants | 8 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants | 19 Participants | 18 Participants | 17 Participants | 73 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 2 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 15 Participants | 10 Participants | 14 Participants | 48 Participants |
| Race (NIH/OMB) More than one race | 6 Participants | 5 Participants | 5 Participants | 1 Participants | 17 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 5 Participants | 9 Participants | 8 Participants | 31 Participants |
| Region of Enrollment United States | 27 participants | 25 participants | 26 participants | 25 participants | 103 participants |
| Sex: Female, Male Female | 18 Participants | 18 Participants | 19 Participants | 21 Participants | 76 Participants |
| Sex: Female, Male Male | 9 Participants | 7 Participants | 7 Participants | 4 Participants | 27 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 / 26 | 0 / 27 | 0 / 25 | 0 / 25 |
| other Total, other adverse events | 0 / 26 | 0 / 27 | 0 / 25 | 0 / 25 |
| serious Total, serious adverse events | 0 / 26 | 0 / 27 | 0 / 25 | 0 / 25 |
Outcome results
Primary
Asthma Control as Measured by the Asthma Control Test (ACT)
Asthma control represents the degree to which impairment (impact of asthma on patient's daily life) is minimized and the goals of therapy are met. The Asthma Control Test is a participant administered tool for assessing the level of asthma control. Total scores range from 5 to 25, with a score of 20 to 25 indicating well-controlled asthma, a score of 16 to 19 indicating asthma that was not well controlled, and a score of 5 to 15 indicating very poorly controlled asthma. The Asthma Control Test has a score range of 5 to 25 with higher scores indicating better control.
Time frame: Follow up is up to 3 months.
Population: Participants with analyzable follow-up data at 3 months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Enhanced Usual Care | Asthma Control as Measured by the Asthma Control Test (ACT) | 18.77 units on a scale | Standard Deviation 3.82 |
| Rescue Inhaled Corticosteroids | Asthma Control as Measured by the Asthma Control Test (ACT) | 18.96 units on a scale | Standard Deviation 3.72 |
| Azithromycin | Asthma Control as Measured by the Asthma Control Test (ACT) | 20.45 units on a scale | Standard Deviation 3.46 |
| Rescue Inhaled Corticosteroids and Azithromycin | Asthma Control as Measured by the Asthma Control Test (ACT) | 20.14 units on a scale | Standard Deviation 3.47 |
Secondary
Asthma Quality of Life Questionnaire (AQLQ) as Measured by the Juniper Mini Asthma Quality of Life Questionnaire
The Asthma Quality of Life Questionnaire is a participant-administered tool for assessing functional impairment. Total scores range from 1 to 7, with a score of 7=no impairment and 1=maximum impairment.
Time frame: Total follow-up period is up to 3 months per participant.
Population: Participants with analyzable survey data at 3 months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Enhanced Usual Care | Asthma Quality of Life Questionnaire (AQLQ) as Measured by the Juniper Mini Asthma Quality of Life Questionnaire | 5.25 units on a scale | Standard Deviation 1.26 |
| Rescue Inhaled Corticosteroids | Asthma Quality of Life Questionnaire (AQLQ) as Measured by the Juniper Mini Asthma Quality of Life Questionnaire | 5.3 units on a scale | Standard Deviation 1.34 |
| Azithromycin | Asthma Quality of Life Questionnaire (AQLQ) as Measured by the Juniper Mini Asthma Quality of Life Questionnaire | 5.59 units on a scale | Standard Deviation 1 |
| Rescue Inhaled Corticosteroids and Azithromycin | Asthma Quality of Life Questionnaire (AQLQ) as Measured by the Juniper Mini Asthma Quality of Life Questionnaire | 5.27 units on a scale | Standard Deviation 1.14 |