Clinical trial NCT06272370: Individualizing Treatment for Asthma in Primary Care
Official title: Individualizing Treatment for Asthma in Primary Care
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Asthma
Bronchial Diseases
Respiratory Tract Infections
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Immune System Diseases
Keywords: asthma
Lead sponsor: DARTNet Institute
Sponsor class: OTHER_GOV
Collaborators: name: Penn State University
name: Icahn School of Medicine at Mount Sinai
name: University of Colorado, Denver
name: RAND
name: University of Washington
name: Rutgers University
name: University of North Carolina
name: Brigham and Women's Hospital
name: Reliant Medical Group
name: Kelsey Research Foundation
name: Wake Forest University Health Sciences
First posted: 2024-02-22
Enrollment: 103
Sex: ALL
Minimum age (years): 12
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: patient randomized trial of three different drug combinations
Primary purpose: HEALTH_SERVICES_RESEARCH

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Asthma Control as Measured by the Asthma Control Test (ACT)
timeFrame: Follow up is up to 3 months.
Secondary outcomes:
measure: Asthma Quality of Life Questionnaire (AQLQ) as Measured by the Juniper Mini Asthma Quality of Life Questionnaire
timeFrame: Total follow-up period is up to 3 months per participant.
Other outcomes:
Locations:
city: Aurora
country: United States
facility: DARTNet Insitute
state: Colorado
Study officials:
affiliation: DARTNet Institute
name: Wilson D Pace, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Penn State University
name: David T Mauger, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: Global Initiative for Asthma. Global strategy for asthma management and prevention 2023 report. Accessed February 10, 2024. https://ginasthma.org/2023-gina-main-report/