Clinical trial NCT03373045: Observational Study of Characteristics, Treatment and Outcomes With Severe Asthma in the United States (CHRONICLE)
Official title: The CHRONICLE Study: A Longitudinal Prospective Observational Study of the Characteristics, Treatment Patterns and Health Outcomes of Individuals With Severe Asthma in the United States
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Asthma
Keywords: Severe asthma
Monoclonal antibody
Corticosteroid
Non-interventional
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Parexel
name: MedImmune LLC
First posted: 2017-12-14
Enrollment: 4519
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: It is estimated that at least 1500 patients in the US with a confirmed diagnosis of severe asthma will be enrolled by a diverse set of asthma specialists (eg, allergists and pulmonologists who treat asthma) from academic and community-based centers.

Brief summary: The CHRONICLE Study is a multi-center, non-interventional, prospective cohort study of adults with severe asthma who do not achieve control with high-dose inhaled corticosteroid (ICS) therapy with additional controllers and/or require systemic corticosteroid or monoclonal antibody therapy. Data will be collected from the healthcare provider in a uniform manner for every patient enrolled using an electronic case report form (eCRF). Data will be collected monthly from patients via web-based surveys. Patients will be followed until study discontinuation or the patient withdraws from the study or death, whichever occurs first. The expectation is that patients will be followed for a period of at least 3 years.

Detailed description: The CHRONICLE Study is a multi-center, non-interventional, prospective cohort study of adults with severe asthma who do not achieve control with high-dose ICS therapy with additional controllers and/or require systemic corticosteroid or monoclonal antibody therapy. This study will provide a contemporary description of the epidemiology and medical management of United States adults with severe asthma who have not achieved control with high-dose ICS therapy and additional controllers. Additionally, the study will describe the use of and outcomes associated with recently approved monoclonal antibody therapies for severe asthma. Patients will be enrolled from a diverse population of academic and community-based specialist centers across the US. Data will be collected in a naturalistic manner and patient management will not be influenced by the study protocol. At least 1500 patients in the US with a confirmed diagnosis of severe asthma will be enrolled by a diverse set of asthma specialists (eg, allergists and pulmonologists who treat asthma) from academic and community-based centers. Basic de-identified information will be collected for all patients meeting study inclusion criteria, including those not approached for enrollment or who decline enrollment, to enable an assessment of the enrolled and non-enrolled populations. This information will include age, sex, insurance status, age at asthma diagnosis, class of asthma treatment per study inclusion criteria, number of asthma exacerbations in the past 12 months, study eligibility, whether the patient was approached for enrollment, study enrollment status, and reason for not enrolling for those who are approached but do not enroll. Patient-reported asthma control (Asthma Control Test \[ACT\]), asthma exacerbations, and treatment adherence will be solicited monthly. Patient-reported information on asthma-related healthcare utilization, global evaluation of treatment effectiveness (GETE), and work productivity (Work Productivity and Activity Impairment Asthma questionnaire \[WPAI-Asthma\]) will be collected at baseline and approximately every 3 months. Detailed information on asthma-related quality of life (Saint George's Respiratory Questionnaire \[SGRQ\]) as well as presence of an asthma treatment plan will be collected from patients approximately every 6 months. All of the questionnaires will be collected via web-based surveys. Patients will then be followed until study discontinuation or the patient withdraws from the study or death, whichever occurs first. The expectation is that patients will be followed for a period of at least 3 years.

Eligibility criteria: Inclusion Criteria:

1. Individuals with a diagnosis of severe asthma for at least 12 months prior to enrollment and confirmed by the Investigator not to be due to alternative diagnoses.

2. Currently receiving care from specialist physicians (eg, pulmonologists and or allergists) at the Investigator's or sub-investigator's site.

3. 18 years of age and older. 4. Meeting at least one of the following three criteria (a, b, or c):

a. Uncontrolled asthma while receiving high-dose ICS with additional controllers.

i. Uncontrolled is defined by meeting at least one of the following (as outlined by ATS/ERS \[American Thoracic Society/European Respiratory Society\] guidelines):

1. Poor symptom control: Asthma Control Questionnaire consistently ≥1.5, ACT \<20 (or "not well controlled" by NAEPP \[National Asthma Education and Prevention Program\]/Global Initiative for Asthma guidelines).
2. Frequent severe exacerbations: two or more bursts of systemic corticosteroids (≥3 days each) in the previous 12 months.
3. Serious exacerbations: at least one hospitalization, intensive care unit stay or mechanical ventilation in the previous 12 months.
4. Airflow limitation: after appropriate bronchodilator withhold FEV1 \<80% predicted (in the face of reduced FEV1/FVC defined as less than the lower limit of normal).

ii. For the purposes of this study, high-dose ICS will be defined as

1. ICS at a cumulative dose of \>500 μg fluticasone propionate equivalents daily as defined in Appendix A, or 2. Highest labeled dose of a combination of ICS/LABA. b. Current use of a Food and Drug Administration (FDA)-approved monoclonal antibody agent for treatment of severe asthma (use is not primarily for an alternative condition).

c. Use of systemic corticosteroids or other systemic immunosuppressants (any dose level) for approximately 50% or more of the prior 12 months for treatment of severe asthma (use is not primarily for an alternative condition).

Exclusion Criteria

1. Not willing and able to sign written informed consent. Consent can be obtained from having a responsible, legally authorized representative acting on patient's behalf.
2. Not fluent in English or Spanish.
3. Inability to complete study follow-up or web-based PROs. If the patient does not have email or web access, minimal assistance from others to access the web-based PRO is permitted (ie receiving the email and/or assisting patient in navigating to the web page); PROs must be completed by the patient.
4. Received an investigational therapy for asthma, allergy, atopic disease, or eosinophilic disease as part of a clinical trial during the 6 months prior to enrollment.

   1. Once enrolled in the CHRONICLE Study, patients can enroll in trials of investigational therapies (as well as other non-interventional studies) as long as they continue to complete study follow-up. If a patient enrolls in a trial of an investigational therapy, the identity (National Clinical Trial \[NCT\] number) of the study and dates of the first and last investigational therapy administrations will be collected. If a patient receives blinded therapy in a trial, the Investigator will request the identity of that therapy at trial conclusion so that treatment information collected for the current study may be updated accordingly.

Primary outcomes:
measure: Healthcare utilization- hospitalizations, clinic Visits, and asthma exacerbations
timeFrame: At baseline, every 6 months, through study completion, assessed up to 7 years.
measure: Asthma treatment
timeFrame: At baseline, every 6 months, through study completion, assessed up to 7 years.
measure: Treatment adherence
timeFrame: At baseline, every 1 month, through study completion, assessed up to 7 years.
measure: Asthma control test (ACT)
timeFrame: Change from baseline, every 1 month, through study completion, assessed up to 4 years.
measure: Patient-reported asthma exacerbations
timeFrame: Change from baseline, every 1 month, through study completion, assessed up to 4 years.
measure: Asthma Impairment and Risk Questionnaire (AIRQ)
timeFrame: At baseline, every 1 month, through study completion, assessed up to 4 years
measure: Work Productivity and Activity Impairment Asthma questionnaire (WPAI-Asthma)
timeFrame: At baseline, every 3 months, through study completion, assessed up to 7 years.
measure: St. George's Respiratory Questionnaire (SGRQ)
timeFrame: At baseline, every 6 months, through study completion, assessed up to 7 years.
measure: Global evaluation of treatment effectiveness (GETE)
timeFrame: At baseline, every 6 months, through study completion, assessed maximum up to 7 years.
measure: Number of Participants With Adverse Events associated with corticosteroid therapy
timeFrame: At baseline, every 6 months, through study completion, assessed up to 7 years.
measure: Relevant respiratory medical events
timeFrame: At baseline, every 6 months, through study completion,assessed up to 7 years.
measure: Respiratory comorbidities
timeFrame: At baseline, every 6 months, through study completion, assessed up to 7 years.
measure: Non-respiratory comorbidities
timeFrame: At baseline, every 6 months, through study completion, assessed up to 7 years.
measure: Events of special interest
timeFrame: At baseline, every 6 months, through study completion, assessed up to 7 years.
measure: Complete blood count with differential including blood eosinophil count.
timeFrame: Change from baseline, every 6 months, through study completion, assessed up to 7 years.
measure: Total immunoglobulin E (IgE)
timeFrame: Change from baseline, every 6 months, through study completion, assessed up to 7 years.
measure: Radiographic changes in asthma evaluation.
timeFrame: Change from baseline, every 6 months, through study completion, assessed up to 7 years.
measure: Forced Vital Capacity (FVC)
timeFrame: Change from baseline, every 6 months, through study completion, assessed up to 7 years.
measure: Forced Expiratory Volume in 1 second (FEV1)
timeFrame: Change from baseline, every 6 months, through study completion, assessed up to 7 years.
measure: Fractional exhaled nitric oxide (FENO)
timeFrame: Change from baseline, every 6 months, through study completion, assessed up to 7 years.
Secondary outcomes:
Other outcomes:
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city: Greenville
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state: Wisconsin
city: Guaynabo
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Study officials:
References:
citation: Panettieri RA Jr, Ledford DK, Chipps BE, Soong W, Lugogo N, Carr W, Mohan A, Carstens D, Genofre E, Trudo F, Ambrose CS. Biologic use and outcomes among adults with severe asthma treated by US subspecialists. Ann Allergy Asthma Immunol. 2022 Oct;129(4):467-474.e3. doi: 10.1016/j.anai.2022.06.012. Epub 2022 Jun 19.
citation: Panettieri RA Jr, Chipps BE, Moore WC, Soong W, Carr WW, Kreindler JL, O'Quinn S, Trudo F, Ambrose CS. Differing perceptions of asthma control and treatment effectiveness by patients with severe asthma and treating subspecialists in the United States. J Asthma. 2022 Sep;59(9):1859-1868. doi: 10.1080/02770903.2021.1963766. Epub 2021 Nov 5.
citation: Trevor J, Lugogo N, Carr W, Moore WC, Soong W, Panettieri RA Jr,, Desai P, Trudo F, Ambrose CS. Severe asthma exacerbations in the United States:: Incidence, characteristics, predictors, and effects of biologic treatments. Ann Allergy Asthma Immunol. 2021 Nov;127(5):579-587.e1. doi: 10.1016/j.anai.2021.07.010. Epub 2021 Jul 15.
citation: Soong W, Chipps BE, O'Quinn S, Trevor J, Carr WW, Belton L, Trudo F, Ambrose CS. Health-Related Quality of Life and Productivity Among US Patients with Severe Asthma. J Asthma Allergy. 2021 Jun 25;14:713-725. doi: 10.2147/JAA.S305513. eCollection 2021.
citation: Ambrose CS, Chipps BE, Moore WC, Soong W, Trevor J, Ledford DK, Carr WW, Lugogo N, Trudo F, Tran TN, Panettieri RA Jr. The CHRONICLE Study of US Adults with Subspecialist-Treated Severe Asthma: Objectives, Design, and Initial Results. Pragmat Obs Res. 2020 Jul 16;11:77-90. doi: 10.2147/POR.S251120. eCollection 2020.
citation: Moore WC, Panettieri RA Jr, Trevor J, Ledford DK, Lugogo N, Soong W, Chipps BE, Carr W, Belton L, Gandhi H, Trudo F, Ambrose CS. Biologic and maintenance systemic corticosteroid therapy among US subspecialist-treated patients with severe asthma. Ann Allergy Asthma Immunol. 2020 Sep;125(3):294-303.e1. doi: 10.1016/j.anai.2020.04.004. Epub 2020 Apr 15.