Inclusion
Item
for inclusion in the study patients should fulfil the following criteria:
boolean
C1512693 (UMLS CUI [1])
Informed Consent
Item
1. provision of signed and dated written informed consent prior to any study specific procedures
boolean
C0021430 (UMLS CUI [1])
Age
Item
2. male or female aged 18 and above at the time of enrolment
boolean
C0001779 (UMLS CUI [1])
Asthma Therapeutic procedure | inhaled steroids | fluticasone Dry Powder Inhaler | Adrenergic beta-2 Receptor Agonists | Leukotriene Antagonists
Item
3. history of physician-diagnosed asthma requiring treatment with medium-to-high dose ics (>250 μg fluticasone dry powder formulation equivalents total daily dose, as defined in gina 2014; see appendix chapter 5) and a second controller medication (eg, laba or leukotriene receptor antagonist). the medium or high dose ics plus laba can be any combination inhaler or 2 separate inhalers. patients must have taken ics (>250
boolean
C0004096 (UMLS CUI [1,1])
C0087111 (UMLS CUI [1,2])
C2065041 (UMLS CUI [2])
C1967989 (UMLS CUI [3])
C2936789 (UMLS CUI [4])
C0595726 (UMLS CUI [5])
Adrenal Cortex Hormones | Theophylline | tiotropium | Leukotriene Antagonists
Item
μg fluticasone or the equivalent daily) plus second controller medication for at least 12 months prior to the date the informed consent is obtained, with or without another controller such as oral corticosteroids (ocs), theophylline, tiotropium, or leukotriene receptor antagonists
boolean
C0001617 (UMLS CUI [1])
C0039771 (UMLS CUI [2])
C0213771 (UMLS CUI [3])
C0595726 (UMLS CUI [4])
post bronchodilator Forced Expiratory Volume in 1 Second Reversibility | Methacholine challenge Positive | Histamine challenge Positive | FEV1 Decrease
Item
4. proof of post-bronchodilator reversibility in fev1 of ≥12% and ≥200 ml (pellegrino et al 2005) documented within 5 years prior to visit 1, or proof of a positive response to a methacholine or histamine challenge (a decrease in fev1 by 20% [pc20] at ≤8 mg/ml) performed according to ats/ers guidelines (american thoracic society 2000) documented within 5 years prior to visit 1. if historical documentation is not available, reversibility or proof of a positive response to a methacholine challenge must be demonstrated and documented at visit 1
boolean
C2599594 (UMLS CUI [1,1])
C3830088 (UMLS CUI [1,2])
C0430567 (UMLS CUI [2,1])
C1446409 (UMLS CUI [2,2])
C0430566 (UMLS CUI [3,1])
C1446409 (UMLS CUI [3,2])
C0748133 (UMLS CUI [4,1])
C0547047 (UMLS CUI [4,2])
Common Cold | Influenza | Asthma
Item
5. must answer "yes" to the question "does a cold or flu make your asthma worse?"
boolean
C0009443 (UMLS CUI [1])
C0021400 (UMLS CUI [2])
C0004096 (UMLS CUI [3])
Exacerbation of severe persistent asthma | Common Cold | Influenza
Item
6. to have had at least two documented severe asthma exacerbations within the last 24 months that were suspected by the patient to have been caused by a common cold or flu and to have had at least one documented severe asthma exacerbation within the last 12 months that was suspected by the patient to have been caused by a common cold or flu
boolean
C3508930 (UMLS CUI [1])
C0009443 (UMLS CUI [2])
C0021400 (UMLS CUI [3])
Postmenopausal state | Female Sterilization | Contraceptive methods Female
Item
7. female patients must be 1 year post-menopausal, surgically sterile, or using an acceptable method of contraception.
boolean
C0232970 (UMLS CUI [1])
C0015787 (UMLS CUI [2])
C0700589 (UMLS CUI [3,1])
C0015780 (UMLS CUI [3,2])
Childbearing Potential | Urine pregnancy test negative
Item
8. negative pregnancy test (urine) for female patients of childbearing potential
boolean
C3831118 (UMLS CUI [1])
C0430057 (UMLS CUI [2])
Compliance behavior
Item
9. motivation (in the investigator's opinion) to complete all study visits, the ability to communicate well with the investigator and be capable of understanding the nature of the research and its treatment including its risks and benefits
boolean
C1321605 (UMLS CUI [1])
Able to read | Able to write | Ability Use of Electronics--Equipment and supplies
Item
10. ability to read and write and use the electronic devices
boolean
C0586740 (UMLS CUI [1])
C0584993 (UMLS CUI [2])
C0085732 (UMLS CUI [3,1])
C1524063 (UMLS CUI [3,2])
C3826411 (UMLS CUI [3,3])
Exclusion Criteria
Item
patients should not enter the study if any of the following exclusion criteria are fulfilled:
boolean
C0680251 (UMLS CUI [1])
Involvement with study planning | Involvement with Study Execution
Item
1. involvement in the planning and/or conduct of the study (applies to both astrazeneca staff and staff at third party vendors or staff at the study sites)
boolean
C1314939 (UMLS CUI [1,1])
C0681871 (UMLS CUI [1,2])
C1314939 (UMLS CUI [2,1])
C0681872 (UMLS CUI [2,2])
Previous Randomization Therapeutic procedure
Item
2. previous randomization to treatment in the present study
boolean
C0205156 (UMLS CUI [1,1])
C0034656 (UMLS CUI [1,2])
C0087111 (UMLS CUI [1,3])
Disease Study Subject Participation Status Limited
Item
3. any condition, including findings in the medical history or in the pre-study assessments that, in the opinion of the investigator, constitutes a risk or a contraindication for the participation of the patient in the study or that could interfere with the study objectives, conduct or evaluation
boolean
C0012634 (UMLS CUI [1,1])
C2348568 (UMLS CUI [1,2])
C0439801 (UMLS CUI [1,3])
Lung diseases | Asthma | Chronic Obstructive Airway Disease | Cystic Fibrosis | Aspergillosis, Allergic Bronchopulmonary
Item
4. lung disease other than asthma (eg, chronic obstructive pulmonary disease, cystic fibrosis, allergic bronchopulmonary aspergillosis)
boolean
C0024115 (UMLS CUI [1])
C0004096 (UMLS CUI [2])
C0024117 (UMLS CUI [3])
C0010674 (UMLS CUI [4])
C0004031 (UMLS CUI [5])
Exacerbation of severe persistent asthma | Upper Respiratory Infections
Item
5. patients with ≥4 severe exacerbations during the last 12 months that the patient suspected were triggered by something else than an upper respiratory tract infection
boolean
C3508930 (UMLS CUI [1])
C0041912 (UMLS CUI [2])
Study Subject Participation Status | Investigational New Drugs | Biological Factors
Item
6. current participation in another clinical trial or participation in a clinical trial where the patient has received a dose of a test product (imp) within 12 weeks prior to entry into the study for small molecules and within 12 months prior to entry into the study for biologicals
boolean
C2348568 (UMLS CUI [1])
C0013230 (UMLS CUI [2])
C0005515 (UMLS CUI [3])
Disease Affecting Research results | Communicable Diseases | Hematological Disease | Malignant Neoplasms | Kidney Diseases | Liver diseases | Coronary heart disease | Cardiovascular Diseases | Cardiac Arrhythmia | Endocrine System Diseases | Gastrointestinal Diseases
Item
7. patients who currently have, or have had within the past 3 months, any significant underlying medical condition(s) that could impact interpretation of results eg, infections, haematological disease, malignancy, renal, hepatic, coronary heart disease or other cardiovascular disease, including arrhythmias, endocrinological or gastrointestinal disease
boolean
C0012634 (UMLS CUI [1,1])
C0392760 (UMLS CUI [1,2])
C0683954 (UMLS CUI [1,3])
C0009450 (UMLS CUI [2])
C0018939 (UMLS CUI [3])
C0006826 (UMLS CUI [4])
C0022658 (UMLS CUI [5])
C0023895 (UMLS CUI [6])
C0010068 (UMLS CUI [7])
C0007222 (UMLS CUI [8])
C0003811 (UMLS CUI [9])
C0014130 (UMLS CUI [10])
C0017178 (UMLS CUI [11])
Abnormal vital signs
Item
8. abnormal vital signs, after at least 10 minutes supine rest, defined as any of the following:
boolean
C0277804 (UMLS CUI [1])
Systolic Pressure | Age
Item
in patients < 60 years old, systolic blood pressure <90 mmhg or ≥150 mmhg
boolean
C0871470 (UMLS CUI [1])
C0001779 (UMLS CUI [2])
Systolic Pressure | Age
Item
in patients > 60 years old, systolic blood pressure <90 mmhg or ≥160 mmhg
boolean
C0871470 (UMLS CUI [1])
C0001779 (UMLS CUI [2])
Diastolic blood pressure
Item
diastolic blood pressure <50 mmhg or ≥100 mmhg
boolean
C0428883 (UMLS CUI [1])
heart rate | beats per minute
Item
hr <45 or >95 beats per minute
boolean
C0018810 (UMLS CUI [1])
C0439385 (UMLS CUI [2])
Resting ECG Changes Abnormal | 12 lead ECG Abnormal | qtc interval Changing | ST segment ECG: T wave abnormal | Left Ventricular Hypertrophy
Item
9. any clinically important abnormalities in rhythm, conduction or morphology of the resting ecg and any abnormalities in the 12-lead ecg that, as considered by the investigator, may interfere with the interpretation of qtc interval changes, including abnormal st-t-wave morphology (particularly in the protocol defined primary lead) or left ventricular hypertrophy
boolean
C3897699 (UMLS CUI [1,1])
C0205161 (UMLS CUI [1,2])
C0430456 (UMLS CUI [2,1])
C0205161 (UMLS CUI [2,2])
C0489625 (UMLS CUI [3,1])
C0392747 (UMLS CUI [3,2])
C1287081 (UMLS CUI [4,1])
C0438167 (UMLS CUI [4,2])
C0149721 (UMLS CUI [5])
QTcF Prolongation | QTcF Shortened | Family history of long QT syndrome
Item
10. prolonged qtcf >450 ms (for both gender) or shortened qtcf <340 ms or family history of long qt syndrome
boolean
C3828431 (UMLS CUI [1])
C3828430 (UMLS CUI [2])
C3839836 (UMLS CUI [3])
Shortened PR interval | PQ interval shortened | Ventricular preexcitation
Item
11. pr(pq) interval shortening <120ms (pr<120 ms but >110 ms is acceptable if there is no evidence of ventricular pre-excitation).
boolean
C0520878 (UMLS CUI [1])
C3854646 (UMLS CUI [2])
C0559106 (UMLS CUI [3])
Prolonged PR interval | Electrocardiogram PQ interval prolonged | Intermittent Second degree atrioventricular block | Intermittent Complete atrioventricular block | Atrioventricular [AV] dissociation
Item
12. pr(pq) interval prolongation (>240ms), intermittent second or third degree av block, or av dissociation
boolean
C0600125 (UMLS CUI [1])
C0858527 (UMLS CUI [2])
C0205267 (UMLS CUI [3,1])
C0264906 (UMLS CUI [3,2])
C0205267 (UMLS CUI [4,1])
C0151517 (UMLS CUI [4,2])
C2882262 (UMLS CUI [5])
QRS complex duration | Intermittent Bundle-Branch Block | persistent Bundle-Branch Block
Item
13. qrs duration >120ms including persistent or intermittent bundle branch block
boolean
C0429025 (UMLS CUI [1])
C0205267 (UMLS CUI [2,1])
C0006384 (UMLS CUI [2,2])
C0205322 (UMLS CUI [3,1])
C0006384 (UMLS CUI [3,2])
Implantable defibrillator | permanent pacemaker | Tachycardia, Ventricular | Heart Atrium Tachyarrhythmia
Item
14. patients with implantable cardiac defibrillator (icd) or a permanent pacemaker and patients with symptomatic ventricular and / or atrial tachyarrhythmias
boolean
C0162589 (UMLS CUI [1])
C0281945 (UMLS CUI [2])
C0042514 (UMLS CUI [3])
C0018792 (UMLS CUI [4,1])
C0080203 (UMLS CUI [4,2])
Angina, Unstable | Stable angina | Canadian Cardiovascular Society classification of angina | Myocardial Infarction | Cerebrovascular accident
Item
15. patients with unstable angina pectoris or stable angina pectoris classified higher than canadian cardiovascular society (css) class ii or a myocardial infarction or stroke within 6 months
boolean
C0002965 (UMLS CUI [1])
C0340288 (UMLS CUI [2])
C1277207 (UMLS CUI [3])
C0027051 (UMLS CUI [4])
C0038454 (UMLS CUI [5])
Heart failure Hospitalization | New York Heart Association Classification
Item
16. history of hospitalization within 12 months caused by heart failure or a diagnosis of heart failure higher than new york heart association (nyha) class ii
boolean
C0018801 (UMLS CUI [1,1])
C0019993 (UMLS CUI [1,2])
C1275491 (UMLS CUI [2])
Hypersensitivity Interferon beta-1a | Hypersensitivity Pharmaceutical Excipient
Item
17. history of hypersensitivity to natural or recombinant interferon beta-1a or to any of the drug preparation excipients
boolean
C0020517 (UMLS CUI [1,1])
C0254119 (UMLS CUI [1,2])
C0020517 (UMLS CUI [2,1])
C0015237 (UMLS CUI [2,2])
Biological Factors | omalizumab
Item
18. received any marketed biologic agent (eg, omalizumab) within 12 months or 5 times the half-life (whichever is the longer) of the agent prior to enrolment
boolean
C0005515 (UMLS CUI [1])
C0966225 (UMLS CUI [2])
Depressive disorder | Feeling suicidal | Severe depression | H/O: depression | Hospitalization | Referral to psychiatry service
Item
19. significant history of depressive disorder or suicidal ideation. specifically; individuals with current severe depression (ie, a low mood, which pervades all aspects of life and an inability to experience pleasure in activities that formerly were enjoyed); individuals with a past history of depression that required hospitalization or referral to psychiatric services in the past 5 years; individuals who currently feel suicidal or have attempted suicide in the past
boolean
C0011581 (UMLS CUI [1])
C0424000 (UMLS CUI [2])
C0588008 (UMLS CUI [3])
C0455503 (UMLS CUI [4])
C0019993 (UMLS CUI [5])
C0420390 (UMLS CUI [6])
H/O: epilepsy | Age | Febrile Convulsions
Item
20. history of epilepsy or seizures after the age of 5 years, other than febrile childhood seizure(s)
boolean
C0455511 (UMLS CUI [1])
C0001779 (UMLS CUI [2])
C0009952 (UMLS CUI [3])
Substance Use Disorders
Item
21. history of drug or alcohol abuse within 12 months prior to enrolment
boolean
C0038586 (UMLS CUI [1])
High enzyme level in serum Hepatic
Item
22. patients who have hepatic serum enzyme levels ≥2.5 times the normal range
boolean
C0476322 (UMLS CUI [1,1])
C0205054 (UMLS CUI [1,2])
Hepatitis B surface antigen positive | Hepatitis C antibody test positive | HIV Seropositivity
Item
23. positive test for serum hepatitis b surface antigen, hepatitis c antibody, or hiv
boolean
C0149709 (UMLS CUI [1])
C1277805 (UMLS CUI [2])
C0019699 (UMLS CUI [3])
smoking cigarettes: ____ pack-years history
Item
24. patients with a smoking history of ≥20 pack-years (1 pack year = 20 cigarettes smoked per day for one year)
boolean
C2230126 (UMLS CUI [1])
Pregnancy Urine dipstick test | Breast Feeding | Pregnancy, Planned
Item
25. female who is breast-feeding, pregnant (verified by urine dipstick pregnancy test) or intends to become pregnant during the study
boolean
C0032961 (UMLS CUI [1,1])
C0430370 (UMLS CUI [1,2])
C0006147 (UMLS CUI [2])
C0032992 (UMLS CUI [3])
Unable Spirometry
Item
26. patients who are unable to demonstrate an acceptable spirometry technique
boolean
C1299582 (UMLS CUI [1,1])
C0037981 (UMLS CUI [1,2])
Study Subject Participation Status | Drug Evaluation
Item
27. patients that have previously been included in studies evaluating the investigational medicinal product
boolean
C2348568 (UMLS CUI [1])
C0013175 (UMLS CUI [2])