Clinical trial NCT03984253: Swiss Severe Asthma Register
Official title: Swiss Severe Asthma Register
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Severe Asthma
Keywords: Asthma
Severe
Register
Lead sponsor: Cantonal Hosptal, Baselland
Sponsor class: OTHER
Collaborators: name: AstraZeneca
name: GlaxoSmithKline
name: Lungenliga Schweiz
name: Novartis
First posted: 2019-06-12
Enrollment: 600
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients presenting to participating study center (pulmonologists in private practice or in pulmonary departments in hospital within Switzerland)

Brief summary: Asthma is one of the most common chronic diseases. Asthma is characterized by chronic airway inflammation and associated with airway hyperresponsiveness and reversible airflow obstruction. The variability of airway obstruction is triggered by different factors that lead to a variety of different asthma phenotypes and subtypes. The various classification options for asthma (e.g. severity, by the predominantly existing inflammation or according to triggers), reflect its heterogeneity.

Despite improved therapeutic methods, the prevalence and morbidity of asthma has increased worldwide in the last years. Asthma is a serious and growing global health problem with around 300 million people affected, independent of age or sex. Estimated 250'000 people die prematurely each year due to their asthma.

Based on the SAPALDIA-study, the prevalence of Asthma in Switzerland is approximately 2-8%. Asthma is considered as a major factor in healthcare cost with up to CHF 1.2 billion per year. Asthma is not only a financial burden to a system; it affects the individual Quality of life negatively. Often health care professionals and patients underestimate the severity of the disease and overestimate asthma control. Severe asthma should not be equated with uncontrolled asthma. To reach a satisfying asthma control numerous factors need to be taken into consideration. Severe asthma is often associated with a high risk of frequent, severe exacerbations, which can even lead to death.

Several severe asthma cohorts and registries already exists and are reported in the literature. The aim of such registries is in general data collection and a better understanding of the disease. So far, most epidemiological studies on severe asthma are cross-sectional with no follow up measures. Only a few studies did repeated measures using the same methods.

Approximately 5% of all Asthma Patients suffers from severe asthma. These patients require systematic assessment and specialist care in dedicated respiratory centres. These centres have a key role in improving the outcome for severe asthma patients. At the same time they act as gatekeepers to ensure appropriate access to new, expensive therapies, this includes antibody treatment and interventional methods such as thermoplasty. These treatments require careful monitoring. It is important to ensure that they are given to the right population. Special assessment to monitor the efficacy and to prevent inappropriate prescribing, exposure of patients to unnecessary risks and excessive costs is indicated.

For all the mentioned reasons a Swiss Severe Asthma Register and a collaboration with an already existing register is needed to prospectively collect data about severe asthma in Switzerland.

Detailed description: The overall objective is to establish a clinical register for patients with severe asthma. Since the number of patients with severe asthma at a single center is usually low, it will be important to collect data in a multi-center system to optimize the diagnostic evaluation and treatment of patients with severe asthma. So far, there is little reliable information about the frequency, phenotype and therapy of patients with severe asthma. The construction of a clinical register should close this gap. The primary objective is to show changes in symptoms control during follow up period and at study end by using the Asthma Control Test (ACT). Secondary endpoints are to collect data to better understand asthma's natural history in patients with severe asthma. The examination will be based on the assessment of the parameters specified under "outcomes".

Patients presenting to participating study center (pulmonologists in private practice or in pulmonary departments in hospital within Switzerland) with severe asthma will be asked to take part in this study when corresponding to the eligibility criteria. All patients with severe asthma will be included in the register only after detailed information and written consent. After four months (for specific therapies) and after 12 months, patients should be re-evaluated for up to 15 years. These follow-up data will also be recorded in the register. During the follow-up visits, the same parameters will be collected as during the initial Baselineexamination (some parameters will be omitted, for example, therapy received or requested for the defined period of the last 12 months, etc.). Severe asthma patients receiving a new specific therapy, e.g. obtained with antibodies, but who cannot be included in the register with the complete parameter profile due to time or capacity reasons of the centers, should be recorded at least with defined basic data and a reduced number of parameters in the register. These parameters include according to the specific asthma approved specific therapies, socio-demographic data, lung function values, laboratory values, parameters of asthma control, smoking status and add-on- therapy. This should make it possible to record a subgroup of severe asthmatics that are suitable for antibody therapy and at the same time offer the attending physician the opportunity to adequately document these complex and expensive therapies by recording the defined parameters. In these patients, an evaluation of the therapy response should be carried out after four months and documented in the register. Thereafter, there is an annual follow-up. At any time, these patients can be transferred to the full version of the register by entering the missing parameters. Patients for whom only the basic data is available (basic version) as well as patients with complete parameter profile in the register are kept in the same database and can be evaluated together. In general, no register-specific examinations will be carried out, but only parameters anyway recorded routinely.

Since this is a cohort study, no sample size calculation can be calculated. Evaluations are carried out continuously. The collective of the data should be described by descriptive statistics concerning the basic data as well as the data of the function diagnostics. Subentities of severe asthma should be identified by a cluster analysis.

Eligibility criteria: Inclusion Criteria:

* In- and outpatients
* Age ≥ 0 year
* Informed consent as documented by signature

Adults:

"Asthma which requires treatment with guidelines suggested medications for GINA steps 4-5 asthma:

* High level therapy:

  1. high dose ICS with ≥ 1000 μg beclomethasone (powder) or equivalent in combination with LABA or leukotriene modifier/theophylline) for the previous year or
  2. Daily long-term therapy with systemic corticosteroids (CS) for ≥50% of the previous year to prevent it from becoming "uncontrolled" or which remains "uncontrolled" despite this therapy or
  3. Therapy with monoclonal antibodies independent from the co-therapy
* Middle level therapy:

Protokollsynopsis SAR Version 01 16.01.2019 Seite 4/10 a) Daily long-term therapy with medium-to high-dose ICS (≥500 μg Beclomethason (powder) or equivalent in combination with LABA or leukotriene modifier/theophylline) for the previous year and uncontrolled asthma defined as at least one of the following:

* Poor symptom control: ACQ consistently \>1.5, ACT \<20 (or "not well controlled" by NAEPP/GINA guidelines).
* Frequent severe exacerbations: two or more bursts of systemic CS (\>3 days each) in the previous year.
* Serious exacerbations: at least one hospitalization, ICU stay or mechanical ventilation in the previous year.
* 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).
* Controlled asthma that worsens on tapering of these high doses of ICS or systemic CS (or additional biologics). The presence of any one of the following exclusion criteria will lead to exclusion of the patients:
* Life-expectancy \<6 months
* Insufficient knowledge of project language

Children:

The criteria for severe or difficult asthma in children and adolescents are considered fulfilled in the case of insufficient symptom control in the last year despite medium/high antiinflammatory long-term therapy:

* age 0-18 years, at time of inclusion
* diagnosis of bronchial asthma made by a physician
* differential diagnoses excluded
* good compliance and trained inhalation technique
* treatment with biological approved for the treatment of severe asthma (currently only omalizumab) or

Proof of:

a) Positive Bronchodilation-test (≥12% increase in FEV1 after SABA) or b) Significant bronchial hyperresponsiveness after nonspecific provocation (e.g., with Methacholine or treadmill) according to ATS criteria (AJRCCM 2000)

* High level of therapy:

  1. Prolonged therapy with high dose inhaled steroid (ICS) (\> 400 μg Budesonide equivalent /\> 200 μg fluticasone alone); or
  2. Daily long-term therapy with medium- to high-dose ICS (≥ 400 μg Budesonide equivalent / ≥200 μg fluticasone) in combination with long-acting betaagonists and / or leukotriene receptor antagonist and / or theophylline; or
  3. Therapy with oral steroids fixed ≥3 last months.
* Insufficient asthma control

  a) Inadequate symptom control after NVL in the last 4 weeks: Protokollsynopsis SAR Version 01 16.01.2019 Seite 5/10
  * ≥3 x weekly asthma symptoms or use of ondemand medication; Or:
  * limited activity due to asthma; Or:
  * any symptoms at night; or b. Exacerbation(s) ≥1 last year that required treatment with systemic steroids and / or inpatient treatment c. limited lung function:
  * pathological Tiffeneau quotient or FEV1 at inclusion.
* Submission of a written consent (parent/ legal guardian).

Exclusion Criteria:

* Life-expectancy \<6 months · Insufficient knowledge of project language

Primary outcomes:
measure: Symptom Control
timeFrame: Baseline, four months, yearly for up to 15 years
Secondary outcomes:
measure: Exacerbations
timeFrame: Baseline, four months, yearly for up to 15 years
measure: Utilization of the health care system
timeFrame: Baseline, four months, yearly for up to 15 years
measure: Quality of Life Questionnaire
timeFrame: Baseline, four months, yearly for up to 15 years
measure: Symptoms and health-related quality of life
timeFrame: Baseline, four months, yearly for up to 15 years
measure: Changes in Medication
timeFrame: Baseline, four months, yearly for up to 15 years
measure: Forced Vital Capacity (FVC)
timeFrame: Baseline, after four months, and after 12 months, then every year up to 15 years
measure: Forced Exahled Volume in 1 second (FEV1)
timeFrame: Baseline, after four months, and after 12 months, then every year up to 15 years
measure: Tiffeneau Test
timeFrame: Baseline, after four months, and after 12 months, then every year up to 15 years
measure: Fraction of exhaled nitric oxide, FENO
timeFrame: Baseline, after four months, and after 12 months, then every year up to 15 years
measure: Blood Gas Aanalysis
timeFrame: Baseline, four months, yearly for up to 15 years
measure: Leucozytes
timeFrame: Baseline, four months, yearly for up to 15 years
measure: Neutrophilic granulocytes
timeFrame: Baseline, four months, yearly for up to 15 years
measure: Eosinophilic granulocytes
timeFrame: Baseline, four months, yearly for up to 15 years
measure: Mortality
timeFrame: Baseline, four months, yearly for up to 15 years
Other outcomes:
Locations:
city: Liestal
country: Switzerland
facility: Cantonal Hospital Baselland Liestal
state: BL
city: Bern
country: Switzerland
facility: Universitätsklinik für Pneumologie, Inselspital
city: Chur
country: Switzerland
facility: Pneumologie, Kantonsspital Graubünden
city: Davos
country: Switzerland
facility: Klinik für Pneumologie, Hochgebirgsklinik Davos
city: Genf
country: Switzerland
facility: Hôpitaux Universitaires Genève
city: Lausanne
country: Switzerland
facility: Centre hospitalier universitaire vaudoise
city: Lugano
country: Switzerland
facility: Pneumologia, Ospedale Civico
city: Sion
country: Switzerland
facility: Hôpital du valais, sion
city: St.Gallen
country: Switzerland
facility: Klinik für Pneumologie und Schlafmedizin, Kantonsspital St.Gallen
city: Zürich
country: Switzerland
facility: Klinik für Pneumologie, Universitätsspital Zürich
Study officials:
affiliation: Kantonsspital Baselland Liestal
name: Jörg Leuppi
role: PRINCIPAL_INVESTIGATOR
References: