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Exacerbations in Severe Asthma Patients: Mechanisms and Biomarkers

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ClinicalTrials.gov Identifier: NCT02660853
Recruitment Status : Completed
First Posted : January 21, 2016
Results First Posted : October 31, 2019
Last Update Posted : December 3, 2019
Sponsor:
Collaborator:
Royal Brompton & Harefield NHS Foundation Trust
Information provided by (Responsible Party):
Imperial College London

Tracking Information
First Submitted Date  ICMJE November 2, 2015
First Posted Date  ICMJE January 21, 2016
Results First Submitted Date  ICMJE September 13, 2019
Results First Posted Date  ICMJE October 31, 2019
Last Update Posted Date December 3, 2019
Study Start Date  ICMJE June 2015
Actual Primary Completion Date June 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 8, 2019)
Percent Predicted FEV1 [ Time Frame: Baseline Visit, 12 months ]
From date of screening visit until date of first asthma exacerbation visit Percent predicted Forced Expiratory Volume in First Second
Original Primary Outcome Measures  ICMJE
 (submitted: January 20, 2016)
FEV1 [ Time Frame: From date of screening visit until date of first asthma exacerbation visit, assessed up to 12 months ]
Forced Expiratory Volume in First Second
Change History Complete list of historical versions of study NCT02660853 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 8, 2019)
  • Exhaled Breath Condensate [ Time Frame: Baseline Visit, 12 months ]
    pH and free Iron
  • Markers of Oxidative Stress in Urine [ Time Frame: Baseline Visit, 12 months ]
    malondialdehyde (MDA)
  • Markers of Oxidative Stress in Urine [ Time Frame: Baseline Visit, 12 months ]
    8-isoprostanes
  • Sputum Analysis [ Time Frame: From baseline visit and 12 months ]
    Eosinophils as percentage of total count
  • PCR for Respiratory Viruses [ Time Frame: Baseline Visit, 12 months ]
    nasopharyngeal swabs
  • Sputum Microbiome [ Time Frame: Baseline Visit, 12 months ]
  • Corticosteroid Insensitivity in Peripheral Blood Mononuclear Cells [ Time Frame: Baseline Visit, 12 months ]
  • Exhaled Nitric Oxide [ Time Frame: Baseline Visit, 12 months ]
  • Exhaled Hydrogen Sulphide [ Time Frame: Baseline Visit, 12 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: January 20, 2016)
  • Exhaled Breath Condensate [ Time Frame: From date of screening visit until date of first asthma exacerbation visit, assessed up to 12 months ]
    pH and free Iron
  • Markers of Oxidative Stress in Urine [ Time Frame: From date of screening visit until date of first asthma exacerbation visit, assessed up to 12 months ]
    malondialdehyde (MDA)
  • Markers of Oxidative Stress in Urine [ Time Frame: From date of screening visit until date of first asthma exacerbation visit, assessed up to 12 months ]
    8-isoprostanes
  • Sputum Analysis [ Time Frame: From date of screening visit until date of first asthma exacerbation visit, assessed up to 12 months ]
    Inflammatory cell count
  • PCR for Respiratory Viruses [ Time Frame: From date of screening visit until date of first asthma exacerbation visit, assessed up to 12 months ]
    nasopharyngeal swabs
  • Sputum Microbiome [ Time Frame: From date of screening visit until date of first asthma exacerbation visit, assessed up to 12 months ]
  • Corticosteroid Insensitivity in Peripheral Blood Mononuclear Cells [ Time Frame: From date of screening visit until date of first asthma exacerbation visit, assessed up to 12 months ]
  • Exhaled Nitric Oxide [ Time Frame: From date of screening visit until date of first asthma exacerbation visit, assessed up to 12 months ]
  • Exhaled Hydrogen Sulphide [ Time Frame: From date of screening visit until date of first asthma exacerbation visit, assessed up to 12 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Exacerbations in Severe Asthma Patients: Mechanisms and Biomarkers
Official Title  ICMJE Exacerbations in Severe Asthma Patients: Mechanisms and Biomarkers
Brief Summary The purpose of this study is to investigate exacerbations in severe asthma with regard to symptoms, lung function, aetiology and biomarkers.
Detailed Description

Patients will be recruited from the Severe Asthma Clinics at Royal Brompton Hospital. At the first visit the investigators will enrol and characterise patients. This will involve asking patients to keep a diary record of PEFR(Peak Expiratory Flow Rate), spirometry, symptom scores, use of beta-agonist reliever and other treatments for 2 weeks. Bloods tests will be taken for markers of systemic inflammation. Markers of oxidative stress will be measured in blood, exhaled breath condensate (EBC) and urine: malondialdehyde (MDA) and 8-isoprostanes. Nitric oxide (NO) levels in exhaled breath will be measured measured twice daily for 2 weeks using a portable hand-held NO meter. If spontaneous sputum is not available, sputum will be induced using ultrasonic nebulization of isotonic saline. Profile of inflammatory cells, cytokines in supernatants, bacteriological culture and microbiome analysis will be measured in the sputum. Patients will be observed over 12 months during which time the number of exacerbations will be recorded on basis of objective measures with evaluation of ACQ (Asthma Control Questionnaire), daily morning and evening PEF (Peak Expiratory Flow). At the earliest onset of exacerbation, the patient will be requested to contact the Asthma Research Unit. Patients will then be asked to attend the laboratory where similar tests to the first visit will be performed. For other exacerbations not studied, the patient will be asked to keep a detailed diary record of symptoms with severity scoring and spirometric and PEF measurements (Exacerbation Diary) over a period of 2 weeks after onset of exacerbation.

As patients with severe asthma are usually very well experienced in what the symptoms of exacerbations are, they will therefore be asked to recognise their own exacerbations. Each patient has their own way of recognising an exacerbation and the investigators will discuss this with each patient and try and establish whether an earlier warning signal is possible. Patients will be asked to record their symptoms and lung function as soon as they feel the onset of an exacerbation, since exacerbations are recognised by the patient as events that are 'clinically identified by being outside the patient's usual range of day-to-day variation'. The patient will receive or administer treatments for the exacerbation as usual without interference from the Research Team except for starting any antibiotic therapies, which will be started (if prescribed) as soon as the visit studies have been completed. Those who have been hospitalized will not be studied, and only those who can attend the Clinical Research Unit will be studied.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Condition  ICMJE Asthma
Intervention  ICMJE Diagnostic Test: FEV1
Participants have FEV1 test
Study Arms  ICMJE Severe Asthma
Patients under Steps 4/5 of Asthma Treatment - SIGN (Scottish Intercollegiate Guidelines Network) / BTS (British Thoracic Society) Guidelines
Intervention: Diagnostic Test: FEV1
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 8, 2019)
25
Original Estimated Enrollment  ICMJE
 (submitted: January 20, 2016)
40
Actual Study Completion Date  ICMJE June 2017
Actual Primary Completion Date June 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • All patients must be able to give informed consent. The definition of severe asthma will be on the basis of

    • Uncontrolled asthma: three or more of the following features present in any week in the previous 4 weeks:

      • Daytime symptoms more than twice per week
      • Any limitation of activities
      • Nocturnal symptoms once or more per week
      • Need for reliever treatment more than twice per week
      • Pre bronchodilator FEV1 <80% predicted or personal best OR
    • Frequent severe exacerbations (≥2 per year) OR
    • Require prescription of daily or alternate day oral corticosteroids (OCS) to achieve asthma control despite the prescription of high dose inhaled corticosteroids (>1000mcg fluticasone propionate daily or equivalent) or maintenance oral corticosteroids plus a long acting beta agonist or one other controller medication (for example anti-cholinergics, leukotriene receptor antagonists or theophylline).

Exclusion Criteria:

  • • Current smoker, or Ex-smoker with a >10 year pack history or having smoked within the past 6 months

    • Significant alternative diagnoses that may mimic or complicate asthma, in particular dysfunctional breathing, panic attacks, and overt psychosocial problems (if these are thought to be the major problem rather than in addition to severe asthma)
    • Significant other primary pulmonary disorders in particular pulmonary embolism, pulmonary hypertension, interstitial lung disease and lung cancer
    • Subjects with emphysema and bronchiectasis should only be excluded if this is thought to be the major pulmonary disorder rather than in addition to severe asthma
    • Diagnosis or current investigation of occupational asthma
    • Any subjects currently participating, or having participated within 3 months of the first dose in a study using a new molecular entity, or the first dose in any other study investigating drugs.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 16 Years to 70 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02660853
Other Study ID Numbers  ICMJE 13/LO/1198
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Imperial College London
Study Sponsor  ICMJE Imperial College London
Collaborators  ICMJE Royal Brompton & Harefield NHS Foundation Trust
Investigators  ICMJE
Principal Investigator: Kian F Chung, MBBS MD FRCP Imperial College London
PRS Account Imperial College London
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP