Individualizing Treatment for Asthma in Primary Care

Phase 4

Completed

Conditions: Lung Diseases, Obstructive
Asthma
Bronchial Diseases
Lung Diseases
Immune System Diseases
Respiratory Tract Infections
Respiratory Hypersensitivity

Interventions: Drug: Inhaled Steroids
Other: Asthma Symptom Monitoring online tools
Drug: Azithromycin Pill

Registration Number: NCT06272370

Lead Sponsor: DARTNet Institute

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 103

Inclusion Criteria

A clinical asthma diagnosis for at least 1 year;
12-75 years of age;
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;
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.)
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

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);
No ICS prescribed for the individual (does not have to be using the ICS inhaler);
Active treatment for hematological or solid organ cancer other than basal cell or skin squamous cell cancer;
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);
On daily or every other day oral steroids for any reason;
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.
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.
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
Rescue Inhaled Corticosteroids and azithromycin	Azithromycin Pill	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
Rescue Inhaled Corticosteroids	Inhaled Steroids	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
Azithromycin	Azithromycin Pill	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
Enhanced Usual Care	Asthma Symptom Monitoring online tools	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
Rescue Inhaled Corticosteroids and azithromycin	Inhaled Steroids	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

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.