History of Changes for Study: NCT03373045

Observational Study of Characteristics, Treatment and Outcomes With Severe Asthma in the United States (CHRONICLE)

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Study Record Versions

Version	Submitted Date	Changes
1	December 8, 2017	None (earliest Version on record)
2	March 7, 2018	Recruitment Status, Study Status and Contacts/Locations
3	April 4, 2018	Study Status, Contacts/Locations and Study Design
4	April 25, 2018	Contacts/Locations and Study Status
5	May 29, 2018	Study Status
6	June 21, 2018	Study Status and Contacts/Locations
7	July 31, 2018	Contacts/Locations and Study Status
8	August 27, 2018	Contacts/Locations and Study Status
9	September 26, 2018	Study Status and Contacts/Locations
10	October 23, 2018	Study Status and Contacts/Locations
11	November 19, 2018	Study Status and Contacts/Locations
12	December 17, 2018	Study Status and Contacts/Locations
13	January 22, 2019	Study Status and Contacts/Locations
14	February 22, 2019	Study Status, Contacts/Locations and Eligibility
15	March 28, 2019	Study Status and Contacts/Locations
16	April 23, 2019	Study Status and Contacts/Locations
17	May 17, 2019	Contacts/Locations and Study Status
18	June 24, 2019	Contacts/Locations and Study Status
19	July 23, 2019	Study Status and Contacts/Locations
20	August 19, 2019	Study Status and Contacts/Locations
21	September 19, 2019	Study Status and Contacts/Locations
22	October 18, 2019	Study Status
23	November 22, 2019	Study Status and Contacts/Locations
24	December 18, 2019	Study Status, Contacts/Locations and Study Design
25	January 27, 2020	Study Status, Contacts/Locations and Study Design
26	February 25, 2020	Study Status, Contacts/Locations and Study Design
27	March 23, 2020	Study Status and Contacts/Locations
28	April 15, 2020	Study Status
29	May 12, 2020	Contacts/Locations and Study Status
30	June 24, 2020	Contacts/Locations, Study Status, Eligibility and Oversight
31	July 10, 2020	Contacts/Locations and Study Status
32	August 6, 2020	Study Status and Contacts/Locations
33	September 11, 2020	Study Status
34	October 7, 2020	Study Status
35	November 9, 2020	Study Status and Contacts/Locations
36	December 7, 2020	Study Status
37	February 9, 2021	Contacts/Locations and Study Status
38	March 10, 2021	Study Status
39	April 7, 2021	Study Status
40	May 7, 2021	Study Status
41	June 7, 2021	Study Status
42	June 10, 2021	Study Status
43	July 13, 2021	Outcome Measures, Study Status and Eligibility
44	August 9, 2021	Study Status
45	September 8, 2021	Study Status
46	October 8, 2021	Study Status
47	November 15, 2021	Study Status
48	December 8, 2021	Study Status
49	February 10, 2022	Study Status
50	March 15, 2022	Study Status
51	April 11, 2022	Study Status
52	May 18, 2022	Study Status
53	June 8, 2022	Contacts/Locations and Study Status
54	July 15, 2022	Study Status, Contacts/Locations, Eligibility and Study Design
55	August 9, 2022	Study Status
56	September 15, 2022	Study Status
57	October 18, 2022	Study Status and Contacts/Locations
58	November 10, 2022	Study Status
59	December 14, 2022	Study Status
60	January 11, 2023	Study Status
61	February 8, 2023	Study Status
62	March 15, 2023	Study Status and Contacts/Locations
63	April 11, 2023	Study Status
64	May 8, 2023	Study Status and Contacts/Locations
65	June 7, 2023	Study Status
66	July 20, 2023	Study Status
67	August 9, 2023	Study Status and Contacts/Locations
68	September 15, 2023	Contacts/Locations and Study Status
69	October 11, 2023	Study Status
70	November 8, 2023	Study Status and Contacts/Locations
71	January 18, 2024	Study Status and Contacts/Locations
72	February 16, 2024	Study Status and Contacts/Locations
73	March 14, 2024	Study Status and Contacts/Locations
74	May 17, 2024	Study Status and Contacts/Locations

Comparison Format:

Merged
Side-by-Side

Study Identification


Unique Protocol ID:	D3250R00023
Brief Title:	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
Secondary IDs:

Study Status


Record Verification:	December 2017
Overall Status:	Not yet recruiting
Study Start:	January 5, 2018
Primary Completion:	December 2, 2022 [Anticipated]
Study Completion:	December 2, 2022 [Anticipated]

First Submitted:	November 20, 2017
First Submitted that Met QC Criteria:	December 8, 2017
First Posted:	December 14, 2017 [Actual]

Last Update Submitted that Met QC Criteria:	December 8, 2017
Last Update Posted:	December 14, 2017 [Actual]

Sponsor/Collaborators


Sponsor:	AstraZeneca
Responsible Party:	Sponsor
Collaborators:	Parexel MedImmune LLC

Oversight


U.S. FDA-regulated Drug:	No
U.S. FDA-regulated Device:	No
Data Monitoring:	No

Study Description

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.

Conditions


Conditions:	Asthma
Keywords:	Severe asthma Monoclonal antibody Corticosteroid Non-interventional

Study Design


Study Type:	Observational [Patient Registry]
Observational Study Model:	Cohort
Time Perspective:	Prospective
Biospecimen Retention:
Biospecimen Description:
Enrollment:	1500 [Anticipated]
Number of Groups/Cohorts	1
Target Follow-Up Duration:	5 Years

Groups and Interventions

Groups/Cohorts	Interventions
Cohort of US adults with severe asthma To describe patient characteristics, treatment patterns, and health outcomes among a large, geographically diverse cohort of US adults with severe asthma who are not controlled on high-dose ICS with additional controllers and/or require chronic systemic corticosteroid or monoclonal antibody therapy.

Outcome Measures


Primary Outcome Measures:
1.	Healthcare utilization- hospitalizations, clinic Visits, and asthma exacerbations [ Time Frame: At baseline, every 6 months, through study completion, assessed up to 7 years. ] Longitudinal changes of Healthcare utilization will be measured using directly collected information from medical, hospital, and pharmacy records to provide a supplementary comprehensive assessment of each patient's healthcare utilization during the study period.
2.	Asthma treatment [ Time Frame: At baseline, every 6 months, through study completion, assessed up to 7 years. ] Asthma medications with dose and start/stop dates including all FDA-approved and standard of care treatments for asthma will be assessed. Longitudinal changes in asthma treatment will also be assessed.
3.	Treatment adherence [ Time Frame: At baseline, every 1 month, through study completion, assessed up to 7 years. ] Extraction of electronic medical, hospital, and pharmacy records will take place at study close and potentially at interim time points to provide a supplementary assessment of each patient's healthcare resource utilization. Longitudinal changes in patient reported treatment adherence will also be assessed.
4.	Asthma control test (ACT) [ Time Frame: Change from baseline, every 1 month, through study completion, assessed up to 7 years. ] Patient-reported asthma symptoms and control will be collected via the ACT questionnaire; a 5 item, self-administered survey that is designed to help the patient describe their asthma and how it affects their daily activities. ACT questionnaire is a 5-point scale (for symptoms and activities: 1=all the time to 5= not at all; for asthma control rating: 1=not controlled at all to 5=completely controlled).
5.	Patient-reported asthma exacerbations [ Time Frame: Change from baseline, every 1 month, through study completion, assessed up to 7 years. ] Asthma exacerbations, the primary analytical definition will be worsening of asthma that leads to any of the following: Use of systemic corticosteroids (or a temporary increase in a stable corticosteroid background dose) for at least 3 days; a single depo-injectable dose of corticosteroids will be considered equivalent to a 3-day course of systemic corticosteroids. An emergency department or urgent care visit (defined as evaluation and treatment for <24 hours in an emergency department or urgent care center) due to asthma that required systemic corticosteroids. An inpatient hospitalization (defined as admission to an inpatient facility and/or evaluation and treatment in a healthcare facility for ≥24 hours) due to asthma.
6.	Work Productivity and Activity Impairment Asthma questionnaire (WPAI-Asthma) [ Time Frame: At baseline, every 3 months, through study completion, assessed up to 7 years. ] Patient-reported productivity impairment assessment including work productivity, activity impairment, and disability will be collected via the WPAI-Asthma. Information will only be collected from procedures that are part of the patient's routine clinical care. WPAI Asthma questionnaire is calculated from 0 to 10 score (0 indicates-Asthma had no effect on my work/ daily activities and 10 indicates Asthma completely prevented me from working score/ doing my daily activities).
7.	St. George's Respiratory Questionnaire (SGRQ) [ Time Frame: At baseline, every 6 months, through study completion, assessed up to 7 years. ] Patient-reported assessment of asthma quality of life will be collected via the SGRQ. SGRQ, a disease specific health-related quality of life measure developed for both asthma and chronic obstructive pulmonary disease (COPD) patients. The SGRQ has 50 items and scores are calculated for 3 domains (symptoms, activity, and impact [psychosocial]) as well as total score. Symptoms - this component is concerned with the effect of respiratory symptoms, their frequency and severity. Impacts (psychosocial) - covers a range of aspects concerned with social functioning and psychological disturbances resulting from respiratory disease Activity - concerned with activities that cause or are limited by breathlessness. Total score summaries the impact of the disease on overall health status. The score is expressed as a percentage of overall impairment, where 100 represents worst possible health status and 0 indicates best possible health status.
8.	Global evaluation of treatment effectiveness (GETE) [ Time Frame: At baseline, every 6 months, through study completion, assessed maximum up to 7 years. ] Patient evaluation of asthma treatment effectiveness will be measured using GETE; a simple measure of perceived treatment effectiveness. The patient will grade the overall treatment effectiveness using the following criteria: excellent (complete control of asthma); good (marked improvement of asthma); moderate (discernible, but limited improvement in asthma); poor (no appreciable change in asthma); or worsening (of asthma).
9.	Number of Participants With Adverse Events associated with corticosteroid therapy. [ Time Frame: At baseline, every 6 months, through study completion, assessed up to 7 years. ] Frequency of relevant medical events such as weight gain (change in BMI), hypertension, dyslipidemia, pneumonia, bone densitometry results, osteoporosis / osteopenia, hip and spinal fractures, avascular necrosis, cataract, glaucoma, diabetes mellitus, cardiovascular disease, Cushing's syndrome, adrenal insufficiency, peptic ulcer disease, myopathy, pseudotumor cerebri, mood disturbance, and insomnia or sleep disturbance.
10.	Relevant respiratory medical events [ Time Frame: At baseline, every 6 months, through study completion,assessed up to 7 years. ] Frequency of relevant respiratory medical events such as pneumonia, pleural effusion, chronic bronchitis, allergic rhinitis.
11.	Respiratory comorbidities [ Time Frame: At baseline, every 6 months, through study completion, assessed up to 7 years. ] Prevalence of respiratory comorbidities such as chronic obstructive pulmonary disease (COPD), bronchiectasis, alpha-1 anti-trypsin deficiency, Churg- Strauss syndrome (eosinophilic granulomatosis with polyangiitis [EGPA]), airway stenosis, cystic fibrosis, allergic bronchopulmonary aspergillosis,chronic eosinophilic pneumonia, bronchiolitis obliterans, immunodeficiency, primary ciliary dyskinesia, atelectasis, arterial hypertension, pulmonary hypertension, neuromuscular disease, allergic rhinitis, chronic rhinosinusitis, and pulmonary embolism.
12.	Non-respiratory comorbidities [ Time Frame: At baseline, every 6 months, through study completion, assessed up to 7 years. ] Prevalence of non-respiratory comorbidities such as diabetes, thyroid disease, cardiac disease, etc.
13.	Events of special interest [ Time Frame: At baseline, every 6 months, through study completion, assessed up to 7 years. ] Frequency of special interest events including new onset malignancy, severe infection, anaphylaxis, or mortality.
14.	Complete blood count with differential including blood eosinophil count. [ Time Frame: Change from baseline, every 6 months, through study completion, assessed up to 7 years. ] To assess complete blood count with differential including blood eosinophil count as a variable for asthma evaluation.
15.	Total immunoglobulin E (IgE) [ Time Frame: Change from baseline, every 6 months, through study completion, assessed up to 7 years. ] To assess total IgE as a variable for asthma evaluation.
16.	Radiographic changes in asthma evaluation. [ Time Frame: Change from baseline, every 6 months, through study completion, assessed up to 7 years. ] Radiographic changes in asthma evaluation included chest X-rays (dates, views, description of major chest findings), Chest computed tomography scan (dates, high resolution (yes/no), intravenous contrast (yes/no), description of major findings). Radiographic asthma evaluation conducted as part of routine care.
17.	Forced Vital Capacity (FVC) [ Time Frame: Change from baseline, every 6 months, through study completion, assessed up to 7 years. ] FEV1 (liters and % predicted) will be assessed as a variable for asthma evaluation.
18.	Forced Expiratory Volume in 1 second (FEV1) [ Time Frame: Change from baseline, every 6 months, through study completion, assessed up to 7 years. ] FEV1 (liters and % predicted) will be assessed as a variable for asthma evaluation.
19.	Fractional exhaled nitric oxide (FENO) [ Time Frame: Change from baseline, every 6 months, through study completion, assessed up to 7 years. ] To assess FENO as a variable for asthma evaluation.

Eligibility


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.
Sampling Method:	Non-Probability Sample
Minimum Age:	18 Years
Maximum Age:
Sex:	All
Gender Based:
Accepts Healthy Volunteers:	No
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 on asthma treatment consistent with GINA Step 4 or 5, receiving high-dose ICS with additional controllers. i. Uncontrolled is defined by meeting at least one of the following (as outlined by ATS/ERS guidelines): Poor symptom control: Asthma Control Questionnaire consistently >1.5, ACT <20 (or "not well controlled" by NAEPP/GINA guidelines) Frequent severe exacerbations: two or more bursts of systemic corticosteroids (>3 days each) in the previous 12 months. Serious exacerbations: at least one hospitalization, intensive care unit stay or mechanical ventilation in the previous 12 months. 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 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. Not fluent in English or Spanish. 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. 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. 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.

Contacts/Locations


Central Contact Person:	AstraZeneca Clinical Study Information Center Telephone: 1-877-240-9479 Email: information.center@astrazeneca.com
Locations:

IPDSharing


Plan to Share IPD:	No

References


Links:
Available IPD/Information: