Individualizing Treatment for Asthma in Primary Care (Full Study)

NCT ID: NCT07052942

Last Updated: 2025-10-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

3200 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-08-01

Study Completion Date

2029-11-15

Brief Summary

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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

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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.

Conditions

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Asthma Asthma Attack Asthma Exacerbations

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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

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

Group Type ACTIVE_COMPARATOR

Inhaled corticosteroid (ICS)

Intervention Type DRUG

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.

Asthma Symptom Monitoring Web-based Application

Intervention Type OTHER

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)

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

Group Type ACTIVE_COMPARATOR

Azithromycin

Intervention Type DRUG

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.

Asthma Symptom Monitoring Web-based Application

Intervention Type OTHER

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).

Enhanced Usual Care

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.

Group Type OTHER

Asthma Symptom Monitoring Web-based Application

Intervention Type OTHER

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).

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

R-ICS either as MART therapy or PARTICS + Azithromycin

Group Type ACTIVE_COMPARATOR

Inhaled corticosteroid (ICS)

Intervention Type DRUG

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

Intervention Type DRUG

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.

Asthma Symptom Monitoring Web-based Application

Intervention Type OTHER

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).

Interventions

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Inhaled corticosteroid (ICS)

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.

Intervention Type DRUG

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.

Intervention Type DRUG

Asthma Symptom Monitoring Web-based Application

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).

Intervention Type OTHER

Eligibility Criteria

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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;
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).
Minimum Eligible Age

13 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Penn State University

OTHER

Sponsor Role collaborator

Icahn School of Medicine at Mount Sinai

OTHER

Sponsor Role collaborator

University of Colorado, Denver

OTHER

Sponsor Role collaborator

RAND

OTHER

Sponsor Role collaborator

University of Washington

OTHER

Sponsor Role collaborator

University of North Carolina

OTHER

Sponsor Role collaborator

Reliant Medical Group

OTHER

Sponsor Role collaborator

Kelsey Research Foundation

OTHER

Sponsor Role collaborator

University of Kansas

OTHER

Sponsor Role collaborator

University of Missouri-Columbia

OTHER

Sponsor Role collaborator

John Peter Smith Health Network

UNKNOWN

Sponsor Role collaborator

Rutgers University

OTHER

Sponsor Role collaborator

AdventHealth

OTHER

Sponsor Role collaborator

Wake Forest University Health Sciences

OTHER

Sponsor Role collaborator

DARTNet Institute

OTHER_GOV

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Wilson D Pace, MD, FAAFP

Role: PRINCIPAL_INVESTIGATOR

DARTNet Institute

Dave Mauger, PhD

Role: PRINCIPAL_INVESTIGATOR

Penn State University

Locations

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DARTNet Institute

Aurora, Colorado, United States

Site Status RECRUITING

University Colorado-Denver

Aurora, Colorado, United States

Site Status RECRUITING

AdventHealth

Orlando, Florida, United States

Site Status NOT_YET_RECRUITING

University of Kansas

Kansas City, Kansas, United States

Site Status NOT_YET_RECRUITING

Reliant Medical Group

Worcester, Massachusetts, United States

Site Status RECRUITING

University of Missouri

Columbia, Missouri, United States

Site Status NOT_YET_RECRUITING

Rutgers Robert Wood Johnson Medical School

New Brunswick, New Jersey, United States

Site Status RECRUITING

Mt. Sinai School of Medicine

New York, New York, United States

Site Status RECRUITING

University North Carolina

Chapel Hill, North Carolina, United States

Site Status RECRUITING

Atrium Health

Charlotte, North Carolina, United States

Site Status RECRUITING

JPS Health Network

Fort Worth, Texas, United States

Site Status NOT_YET_RECRUITING

Kelsey Research Foundation

Houston, Texas, United States

Site Status RECRUITING

University of Washington

Seattle, Washington, United States

Site Status NOT_YET_RECRUITING

Countries

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United States

Central Contacts

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Brian K Manning, MPH

Role: CONTACT

1-866-297-8521 ext. 82

Joel Shields, MA

Role: CONTACT

1-866-297-8521 ext. 84

Facility Contacts

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Jack Westfall, MD

Role: primary

1-800-434-0278 ext. 74

Jill VanWyk, MD

Role: primary

720-682-4413

Richard Rosiello, MD

Role: primary

508-595-2105

Larry Garber, MD

Role: backup

508-425-6132

Jane McElroy, PhD

Role: primary

573-882-4993

Lawrence Kleinman, MD, MPH

Role: primary

732-235-7700

Juan Wisnivesky, MD, DrPH

Role: primary

212-824-7567

Michelle Hernandez, MD

Role: primary

919-966-2333

Hazel Tapp, PhD

Role: primary

704-304-7176

Andrea Price

Role: backup

704-304-7120

Puneet Patni, MD

Role: primary

713-239-4510

References

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

Reference Type 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.

Reference Type BACKGROUND
PMID: 33637072 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33326352 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31917651 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 35213105 (View on PubMed)

Other Identifiers

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PLACER-2021C3-24737-IC_Full

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

PLACER-2021C3-24737-IC_Full

Identifier Type: -

Identifier Source: org_study_id

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