NCT07052942

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
3,200

participants targeted

Target at P75+ for phase_4 asthma

Timeline
43mo left

Started Aug 2025

Longer than P75 for phase_4 asthma

Geographic Reach
1 country

13 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress17%
Aug 2025Nov 2029

First Submitted

Initial submission to the registry

June 30, 2025

Completed
8 days until next milestone

First Posted

Study publicly available on registry

July 8, 2025

Completed
24 days until next milestone

Study Start

First participant enrolled

August 1, 2025

Completed
4.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 15, 2029

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 15, 2029

Last Updated

October 29, 2025

Status Verified

October 1, 2025

Enrollment Period

4.3 years

First QC Date

June 30, 2025

Last Update Submit

October 28, 2025

Conditions

Keywords

Intervention/Treatment

Outcome Measures

Primary Outcomes (1)

  • Rate of Asthma Exacerbations Per Year

    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.

    Follow-up is up to 16 months.

Secondary Outcomes (3)

  • Asthma Control as Measured by the Asthma Control Test (ACT)

    Follow-up is up to 16 months.

  • Asthma Quality of Life Questionnaire (AQLQ) as Measured by the Juniper Mini Asthma Quality of Life Questionnaire

    Follow-up is up to 16 months.

  • 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.

Study Arms (4)

Inhaled corticosteroids as part of rescue therapy (R-ICS)

ACTIVE COMPARATOR

Maintenance And Reliever Therapy (MART), or Patient Activated Reliever Triggered Inhaled Corticosteroids (PARTICS) - this includes budesonide-albuterol (AirSupra)

Drug: Inhaled corticosteroid (ICS)Other: Asthma Symptom Monitoring Web-based Application

Azithromycin (AZ)

ACTIVE COMPARATOR

Azithromycin - 500mg three times per week. Can be reduced to 250 mg three times per week for side effects.

Drug: AzithromycinOther: Asthma Symptom Monitoring Web-based Application

Enhanced Usual Care

OTHER

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.

Other: Asthma Symptom Monitoring Web-based Application

Inhaled corticosteroids as part of rescue therapy (R-ICS) + Azithromycin

ACTIVE COMPARATOR

R-ICS either as MART therapy or PARTICS + Azithromycin

Drug: Inhaled corticosteroid (ICS)Drug: AzithromycinOther: Asthma Symptom Monitoring Web-based Application

Interventions

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.

Inhaled corticosteroids as part of rescue therapy (R-ICS)Inhaled corticosteroids as part of rescue therapy (R-ICS) + Azithromycin

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.

Azithromycin (AZ)Inhaled corticosteroids as part of rescue therapy (R-ICS) + Azithromycin

All participants will be provided access to the Asthma Symptom Monitoring (ASM) tools. ASM can be integrated with electronic health records (EHR) or used as a stand alone application. Participants will answer 5 questions about their asthma each week. If symptoms are problematic, participants can request a call back from a person on their care team. Participants can view a graph of their data, watch videos, and record peak flows. Clinicians and members of the care team can view data in the EHR (not for stand alone web app).

Azithromycin (AZ)Enhanced Usual CareInhaled corticosteroids as part of rescue therapy (R-ICS)Inhaled corticosteroids as part of rescue therapy (R-ICS) + Azithromycin

Eligibility Criteria

Age13 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • A clinical asthma diagnosis for at least 1 year;
  • years of age;
  • 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;
  • 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;
  • 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.
  • 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.

You may not qualify if:

  • Another family member living in the same household already enrolled in study;
  • 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 (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);
  • 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);
  • On daily or every other day oral steroids for any reason;
  • 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);
  • 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.
  • 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;
  • 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).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (13)

DARTNet Institute

Aurora, Colorado, 80045, United States

RECRUITING

University Colorado-Denver

Aurora, Colorado, 80045, United States

RECRUITING

AdventHealth

Orlando, Florida, 32803, United States

NOT YET RECRUITING

University of Kansas

Kansas City, Kansas, 66160, United States

NOT YET RECRUITING

Reliant Medical Group

Worcester, Massachusetts, 01608, United States

RECRUITING

University of Missouri

Columbia, Missouri, 65211, United States

NOT YET RECRUITING

Rutgers Robert Wood Johnson Medical School

New Brunswick, New Jersey, 08901, United States

RECRUITING

Mt. Sinai School of Medicine

New York, New York, 10029, United States

RECRUITING

University North Carolina

Chapel Hill, North Carolina, 27599, United States

RECRUITING

Atrium Health

Charlotte, North Carolina, 28207, United States

RECRUITING

JPS Health Network

Fort Worth, Texas, 76104, United States

NOT YET RECRUITING

Kelsey Research Foundation

Houston, Texas, 77005, United States

RECRUITING

University of Washington

Seattle, Washington, 98105, United States

NOT YET RECRUITING

Related Publications (5)

  • Global Initiative for Asthma. Global strategy for asthma management and prevention 2023 report. Accessed February 10, 2024. https://ginasthma.org/2023-gina-main-report/

    BACKGROUND
  • Calmes D, Huynen P, Paulus V, Henket M, Guissard F, Moermans C, Louis R, Schleich F. Chronic infection with Chlamydia pneumoniae in asthma: a type-2 low infection related phenotype. Respir Res. 2021 Feb 26;22(1):72. doi: 10.1186/s12931-021-01635-w.

    PMID: 33637072BACKGROUND
  • Wenzel SE. Severe Adult Asthmas: Integrating Clinical Features, Biology, and Therapeutics to Improve Outcomes. Am J Respir Crit Care Med. 2021 Apr 1;203(7):809-821. doi: 10.1164/rccm.202009-3631CI.

    PMID: 33326352BACKGROUND
  • Ray A, Camiolo M, Fitzpatrick A, Gauthier M, Wenzel SE. Are We Meeting the Promise of Endotypes and Precision Medicine in Asthma? Physiol Rev. 2020 Jul 1;100(3):983-1017. doi: 10.1152/physrev.00023.2019. Epub 2020 Jan 9.

    PMID: 31917651BACKGROUND
  • Israel E, Cardet JC, Carroll JK, Fuhlbrigge AL, She L, Rockhold FW, Maher NE, Fagan M, Forth VE, Yawn BP, Arias Hernandez P, Kruse JM, Manning BK, Rodriguez-Louis J, Shields JB, Ericson B, Colon-Moya AD, Madison S, Coyne-Beasley T, Hammer GM, Kaplan BM, Rand CS, Robles J, Thompson O, Wechsler ME, Wisnivesky JP, McKee MD, Jariwala SP, Jerschow E, Busse PJ, Kaelber DC, Nazario S, Hernandez ML, Apter AJ, Chang KL, Pinto-Plata V, Stranges PM, Hurley LP, Trevor J, Casale TB, Chupp G, Riley IL, Shenoy K, Pasarica M, Calderon-Candelario RA, Tapp H, Baydur A, Pace WD. Reliever-Triggered Inhaled Glucocorticoid in Black and Latinx Adults with Asthma. N Engl J Med. 2022 Apr 21;386(16):1505-1518. doi: 10.1056/NEJMoa2118813. Epub 2022 Feb 26.

    PMID: 35213105BACKGROUND

MeSH Terms

Conditions

Asthma

Interventions

Azithromycin

Condition Hierarchy (Ancestors)

Bronchial DiseasesRespiratory Tract DiseasesLung Diseases, ObstructiveLung DiseasesRespiratory HypersensitivityHypersensitivity, ImmediateHypersensitivityImmune System Diseases

Intervention Hierarchy (Ancestors)

ErythromycinMacrolidesPolyketidesLactonesOrganic Chemicals

Study Officials

  • Wilson D Pace, MD, FAAFP

    DARTNet Institute

    PRINCIPAL INVESTIGATOR
  • Dave Mauger, PhD

    Penn State University

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Brian K Manning, MPH

CONTACT

Joel Shields, MA

CONTACT

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: The investigators are intentionally avoiding the factorial design framework for the purpose of analysis. This is because the investigators are uncertain about whether the combined treatments will have an additive effect. If the combined effect is less than additive, then the standard main effects analysis based on the factorial design is not optimal. The primary analysis will consist of three hypothesis tests comparing each of the three treatment arms against the control.
Sponsor Type
OTHER GOV
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 30, 2025

First Posted

July 8, 2025

Study Start

August 1, 2025

Primary Completion (Estimated)

November 15, 2029

Study Completion (Estimated)

November 15, 2029

Last Updated

October 29, 2025

Record last verified: 2025-10

Data Sharing

IPD Sharing
Will share

Analyzable data set will be submitted to PCORI at the conclusion of the study. This will include the final cleaned and locked data set that contains all the data used in conducting the analyses reported in the PCORI Final Research Report and is de-identified in accordance with the HIPAA Privacy. Rule (45 C.F.R. § 164.514(b)).

Shared Documents
STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
Time Frame
Anticipated date is no later than 6/31/31.
Access Criteria
Users interested in obtaining study data will need to complete a Restricted Data Use Agreement, specify the reason for the request, and obtain IRB approval or notice of exemption for their research.
More information

Locations