Non-steroidal exacerbated respiratory disease and uncontrolled asthma Respiratory
Conditions
Interventions
Randomisation will be performed centrally and generated by a secure web-based system on a 1:1 basis with stratification for recruiting site and inclusion into the sputum subgroup. Patients will be ran
respectively, as six Omega-3 ethyl ester 90 capsules, taken once daily, or in divided doses, with food.
or
CONTROL ARM: Matched capsules (six) containing palm olein IV 56 taken once daily, or in divi
Sponsors
Norfolk and Norwich University Hospitals NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Aged =18 years. N-ERD does not occur at birth and it rarely occurs in children 2. Diagnosis of N-ERD according to one of: 2.1. Positive aspirin challenge plus history of nasal polyposis or asthma 2.2. More than one typical reaction to NSAIDs or aspirin plus history of nasal polyposis or asthma 2.3. A single typical reaction to NSAIDs or aspirin and a history of nasal polyposis plus moderate to severe asthma* 2.4. History of nasal polyposis plus asthma plus blood eosinophilia (=300 x 10e6/l) or raised FENO (>25 ppb) within last 12 months plus urinary leukotriene E4/creatinine >800 pg/mg 3. ACQ of more than 1.5 as this indicates poor control. This is required to ensure there is a clinical need or a requirement to alter medication 4. Stable disease, as evidenced by a lack of change in asthma therapy within the last 6 weeks *Defined as asthma requiring at least low dose inhaled corticosteroid plus long acting bronchodilator or resulting in at least two asthma attacks per year
Exclusion criteria
Exclusion criteria: 1. Tolerant to aspirin or NSAID with no respiratory or nasal reaction on exposure 2. Significant cardiac disease, respiratory disease or other cause for breathlessness which, according to the principal investigator, contributes to the patient’s symptoms of breathlessness or other respiratory symptoms to a greater degree than the patient’s asthma 3. Severe or uncontrolled co-morbid disease (other than nasal polyps) which is likely to affect the outcome of the study 4. Having had an upper or lower respiratory tract infection requiring antibiotics within four weeks of randomisation 5. Receiving biologic agents 6. Receiving n-3 fatty acid oral supplements or more than two dietary portions of oily fish per week 7. Current smoker or more than 15 pack-year smoking history 8. Consumption of more than 21 units of alcohol per week as alcohol-induced respiratory symptoms are more common in N-ERD. 9. Pregnant or breastfeeding women and those less than 4 weeks postpartum 10. Women of child bearing potential (WOCBP) not using a highly effective form of contraceptive. Pregnancy tests will be required at trial start and at 12 weeks. Highly effective forms of contraception defined as: Methods of birth control which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such, as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence or vasectomized partner. This will apply to all women under 55 years of age unless they are postmenopausal or sterile. Postmenopausal is defined as at least 12 months of spontaneous amenorrhea or 24 weeks of spontaneous amenorrhoea with serum FSH >40 mIU/ml. Surgically sterile is defined as females who have had a hysterectomy, bilateral salpingectomy or bilateral oophorectomy at least 6 weeks prior to enrolment. 11. Participation in the active phase of another CTIMP or within 4 weeks (or the half life of the drug if longer) of last study drug administration. Participation in observatory trials can occur if agreed between the PI of each trial and where this does not impact the patient or the outcomes of either trial 12. Patients unable to give written informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Asthma control measured using the change in asthma control questionnaire (ACQ)-6 between baseline and 24 weeks post-randomisation | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Asthma control measured using the asthma control questionnaire (ACQ)-7 at baseline, 12 weeks and 24 weeks 2. General health-related and disease-specific quality of life measured using the Mini Asthma Quality of Life Questionnaire (mini-AQLQ), Health-related quality of life indicated by the EQ5D-5L questionnaire to estimate quality-adjusted life years; Sino-nasal disease-related quality of life measured using the Sino-Nasal Outcomes Test (SNOT)-22, at baseline, 12 weeks and 24 weeks 3. Lung and nasal function measured using peak nasal inspiratory flow (PNIF) (every 6 weeks, where possible), Peak expiratory flow (PEF) every 6 weeks and Forced expiratory volume (FEV)1 and forced expiratory flow at 50% of vital capacity (FEF50) will be obtained from spirometry at baseline, 12 weeks and 24 weeks. 4. Type 2 airway inflammation measured using the fraction of exhaled nitric oxide (FeNO) at baseline, 12 weeks and 24 weeks; Induced or spontaneous sputum (subgroup) at baseline and 24 weeks; full blood count for assessment of the concentration of eosinophils at baseline, 12 weeks and 24 weeks. 5. Cyclooxygenase pathway: urine analysis for LTE4 and PGD2 measured using radioimmunoassay and corrected for urinary creatinine at baseline and 24 weeks. 6. Adherence measured using the red blood cell fatty acid concentration at baseline, 12 weeks and 24 weeks and; Food frequency questionnaire (FFQ) at baseline and 24 weeks. 7. Specialised pro-resolving mediators (SPM): Induced or spontaneous sputum (subgroup) at baseline and 24 weeks. 8. Asthma attacks and safety: Asthma attacks will be defined as those resulting in death, hospitalisation, A&E attendance, out-of-hours medical contact, or a course or boost in oral corticosteroids (prednisolone) of at least 3 days for asthma. Adverse events will be recorded at each study visit following randomisation. Full blood count, renal and liver function tests, and coagulation for those receiving warfarin will be measured in local laboratories a | — |
Countries
England, United Kingdom
Contacts
Public ContactColin McAlister
Outcome results
None listed