Individualizing Treatment for Asthma in Primary Care (Full Study)

Not Applicable

Not yet recruiting

• Conditions: Asthma; Asthma Attack; Asthma Exacerbations
• Interventions: Drug: Inhaled corticosteroid (ICS); Drug: Azithromycin; Other: Asthma Symptom Monitoring Web-based Application

• Registration Number: NCT07052942
• Lead Sponsor: DARTNet Institute

Brief Summary

While asthma therapy is becoming more individualized based on asthma phenotypes, more research is needed to tailor newer therapies to individuals. Inhaled corticosteroid (ICS) medications are the foundation of care for all individuals with persistent asthma. But ICS use is not without possible long term side effects.

This study will compare two currently available approaches to reduce AEX in primary care patients: (1) use of inhaled corticosteroids (ICS) as part of rescue therapy, also known as MART (Maintenance And Reliever Therapy) or PARTICS (Patient Activated Reliever Trigger Inhaled Corticosteriods) therapy - either of these therapies will be called Rescue-Inhaled Corticosteroids or R-ICS pronounced "Ricks," and (2) use of azithromycin (AZ) as a preventive therapy. These treatments will be studied both individually and in combination.

Detailed Description

Design. Four arm, patient level randomized trial (N=3200). Comparators: Rescue inhaled corticosteroids (R-ICS) versus azithromycin versus R-ICS plus azithromycin versus control patients. All arms will include home monitoring of asthma symptoms using various web application approaches. R-ICS therapy will consist of a corticosteriod/formoterol inhaler, 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 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. Individuals completing either of the azithromycin arms will be offered up to 12 additional months of follow-up after stopping the azithromycin only.

Study Timeline

• Study First Submitted: 2025-06-30
• Study First Submitted QC: 2025-06-30
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-07
• Study First Posted: 2025-07-08
• Last Update Posted: 2025-07-10
• Study Start: 2025-08-01
• Primary Completion: 2029-11-15
• Study Completion: 2029-11-15

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 3200

Inclusion Criteria

1. A clinical asthma diagnosis for at least 1 year;

2. 13-75 years of age;

3. A prescription for an ICS either used regularly, or on an as needed controller, not reliever, schedule - ICS or ICS + LABA or ICS+LABA+LAMA;

4. A current ACT total score of <20 OR an exacerbation requiring 72 hours or more of systemic steroids or a hospitalization of at least 24 hours > 30 days and < 365 days prior to enrollment;

5. 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.);

6. 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.

7. Patients on medications that may interact with azithromycin but are not totally excluded may be enrolled if they agree to a cardiac rhythm strip after consent and prior to randomization (or have an ECG within the prior 24 months as a baseline assessment) and a repeat rhythm strip after one week if randomized to one of the azithromycin arms of the study.

Exclusion Criteria

1. Another family member living in the same household already enrolled in study;
2. 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);
3. No ICS prescribed for the individual (does not have to be using the ICS inhaler);
4. Active treatment for hematological or solid organ cancer other than basal cell or skin squamous cell cancer (if participant is > 12 months out from original therapy and may be on a cancer maintenance drug that is not otherwise contraindicated they are eligible for the study);
5. 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 evidence of prolonged cardiac repolarization on rhythm strip and QT interval or torsades de pointes);
6. On daily or every other day oral steroids for any reason;
7. A course of systemic steroids for an asthma exacerbation or an overnight hospitalization for an asthma exacerbation in the past month (can wait and re-check eligibility after one month);
8. Currently on R-ICS or any antibiotic therapy expected to last more than 30 days. If on antibiotics less than 30 days, individual can enroll after they have stopped their current antibiotic for 72 hours. 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 after being on the stable does of the biologic.
9. 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)- absolute contraindication to eligibility- Full lists in Appendix B;
10. 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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Inhaled corticosteroids as part of rescue therapy (R-ICS)	Inhaled corticosteroid (ICS)	Maintenance And Reliever Therapy (MART), or Patient Activated Reliever Triggered Inhaled Corticosteroids (PARTICS) - this includes budesonide-albuterol (AirSupra)
Inhaled corticosteroids as part of rescue therapy (R-ICS)	Asthma Symptom Monitoring Web-based Application	Maintenance And Reliever Therapy (MART), or Patient Activated Reliever Triggered Inhaled Corticosteroids (PARTICS) - this includes budesonide-albuterol (AirSupra)
Azithromycin (AZ)	Asthma Symptom Monitoring Web-based Application	Azithromycin - 500mg three times per week. Can be reduced to 250 mg three times per week for side effects.
Azithromycin (AZ)	Azithromycin	Azithromycin - 500mg three times per week. Can be reduced to 250 mg three times per week for side effects.
Inhaled corticosteroids as part of rescue therapy (R-ICS) + Azithromycin	Inhaled corticosteroid (ICS)	R-ICS either as MART therapy or PARTICS + Azithromycin
Enhanced Usual Care	Asthma Symptom Monitoring Web-based Application	Participants will be asked to use an online Asthma Symptom Monitoring (ASM) tool to enhance communication with the medical team as well as self-awareness of their asthma symptoms. There are no "study drugs" in this intervention.
Inhaled corticosteroids as part of rescue therapy (R-ICS) + Azithromycin	Asthma Symptom Monitoring Web-based Application	R-ICS either as MART therapy or PARTICS + Azithromycin
Inhaled corticosteroids as part of rescue therapy (R-ICS) + Azithromycin	Azithromycin	R-ICS either as MART therapy or PARTICS + Azithromycin

Primary Outcome Measures

Name	Time	Method
Rate of Asthma Exacerbations Per Year	Follow-up is up to 16 months.	The primary outcome, the rate of asthma exacerbations per year, is defined as the number of exacerbations, emergency room visits, or hospitalizations requiring oral or parenteral corticosteroids, per patient per year, monthly through study completion.

Secondary Outcome Measures

Name	Time	Method
Asthma Control as Measured by the Asthma Control Test (ACT)	Follow-up is up to 16 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.
Asthma Quality of Life Questionnaire (AQLQ) as Measured by the Juniper Mini Asthma Quality of Life Questionnaire	Follow-up is up to 16 months.	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.
Days Per Year Lost From Work or School/ Days Unable to Carry Out Usual Activities Due to Asthma	Follow-up is up to 16 months.	Defined as days not able to work or go to school because of asthma symptoms OR days not able to carry out usual activities due to asthma.

Trial Locations

Locations (13)

DARTNet Institute; 🇺🇸 Aurora, Colorado, United States

University Colorado-Denver; 🇺🇸 Aurora, Colorado, United States

AdventHealth; 🇺🇸 Orlando, Florida, United States

University of Kansas; 🇺🇸 Kansas City, Kansas, United States

Reliant Medical Group; 🇺🇸 Worcester, Massachusetts, United States

University of Missouri; 🇺🇸 Columbia, Missouri, United States

Rutgers Robert Wood Johnson Medical School; 🇺🇸 New Brunswick, New Jersey, United States

Mt. Sinai School of Medicine; 🇺🇸 New York, New York, United States

University North Carolina; 🇺🇸 Chapel Hill, North Carolina, United States

Atrium Health; 🇺🇸 Charlotte, North Carolina, United States

Scroll for more (3 remaining)