Swiss Severe Asthma Register

Severe Asthma Clinical Trial

Official title:

Swiss Severe Asthma Register

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03984253
• Other study ID #: 2018-01553
• Status: Recruiting
• Start date: May 13, 2019
• Est. completion date: February 28, 2034

Study information

• Verified date: February 2023
• Source: Cantonal Hosptal, Baselland
• Contact: Jörg Leuppi
• Phone: +41619252181
• Email: Joerg.leuppi[@]ksbl.ch
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: February 28, 2034
• Est. primary completion date: February 28, 2034
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year and older

Eligibility

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

Related Conditions & MeSH terms

• Asthma
• Severe Asthma

Locations

Country	Name	City	State
Switzerland	Universitätsklinik für Pneumologie, Inselspital	Bern
Switzerland	Pneumologie, Kantonsspital Graubünden	Chur
Switzerland	Klinik für Pneumologie, Hochgebirgsklinik Davos	Davos
Switzerland	Hôpitaux Universitaires Genève	Genf
Switzerland	Centre hospitalier universitaire vaudoise	Lausanne
Switzerland	Cantonal Hospital Baselland Liestal	Liestal	BL
Switzerland	Pneumologia, Ospedale Civico	Lugano
Switzerland	Hôpital du valais, sion	Sion
Switzerland	Klinik für Pneumologie und Schlafmedizin, Kantonsspital St.Gallen	St.Gallen
Switzerland	Klinik für Pneumologie, Universitätsspital Zürich	Zürich

Sponsors (5)

Lead Sponsor	Collaborator
Prof. Dr. Jörg Leuppi	AstraZeneca, GlaxoSmithKline, Lungenliga Schweiz, Novartis

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Symptom Control	Changes in symptom control at baseline and during the follow-up period and at study end using the Asthma Control Test (ACT).	Baseline, four months, yearly for up to 15 years
Secondary	Exacerbations	Number of exacerbation with/without hospitalization	Baseline, four months, yearly for up to 15 years
Secondary	Utilization of the health care system	Number of Visits at one's general practitioner (GP) Number of Visits at a pneumologist/ specialist Number of emergency consultations Number of hospitalizations Number of rehabilitation stays	Baseline, four months, yearly for up to 15 years
Secondary	Quality of Life Questionnaire	Mini Asthma Quality of Life Questionnaire(Mini-AQLQ); 15 Questions, Scale 1 to 7 , Minimum Score 15, Maximum Score 105.; The higher the Score is, the better the quality of life	Baseline, four months, yearly for up to 15 years
Secondary	Symptoms and health-related quality of life	Asthma Control Test 5 Questions, Scale 1- 5, Minimum score 5, max 25, the smaller the score the better is the Asthma control	Baseline, four months, yearly for up to 15 years
Secondary	Changes in Medication	Changes in Medication will be monitored for each subject. Changes in dose in mg Changes in substances if there is a new drug used.	Baseline, four months, yearly for up to 15 years
Secondary	Forced Vital Capacity (FVC)	Changes in FVC in liter and % from the target value	Baseline, after four months, and after 12 months, then every year up to 15 years
Secondary	Forced Exahled Volume in 1 second (FEV1)	Changes in FEV1 in liter and % from the target value	Baseline, after four months, and after 12 months, then every year up to 15 years
Secondary	Tiffeneau Test	Changes in Tiffeneau in % and % from Target Value	Baseline, after four months, and after 12 months, then every year up to 15 years
Secondary	Fraction of exhaled nitric oxide, FENO	Changes in FENO in ppb	Baseline, after four months, and after 12 months, then every year up to 15 years
Secondary	Blood Gas Aanalysis	pO2 in kPa/ mmHg pCO2 in kPa/ mmHg and Bloodoxygensaturation in %	Baseline, four months, yearly for up to 15 years
Secondary	Leucozytes	Changes in Leucozytes in nl	Baseline, four months, yearly for up to 15 years
Secondary	Neutrophilic granulocytes	in nl or %	Baseline, four months, yearly for up to 15 years
Secondary	Eosinophilic granulocytes	in µl or %	Baseline, four months, yearly for up to 15 years
Secondary	Mortality	Mortality rate due to severe Asthma	Baseline, four months, yearly for up to 15 years