The Use of Fractional Exhaled Nitric Oxide in the Identification of Non-adherence in Difficult Asthma

This study has been completed.
Sponsor:
Collaborators:
Queen's University, Belfast
Asthma UK
Northern Ireland Chest Heart & Stroke
Information provided by (Responsible Party):
Liam Heaney, Belfast Health and Social Care Trust
ClinicalTrials.gov Identifier:
NCT01219036
First received: October 12, 2010
Last updated: February 1, 2012
Last verified: February 2012
  Purpose

Asthma usually responds to standard doses of inhaled steroids with or without additional therapies to control their symptoms. However, approximately 5-10% do not respond to this treatment strategy and are referred to as having difficult asthma. Evidence shows that this poor response is not always related to asthma severity with non-adherence to treatment being a common underlying problem, in 35% of subjects. Recognising non-adherence in the clinic is problematic as there is no straightforward objective test to identify it.

Patients attending an asthma clinic whose symptoms are not controlled by standard treatment will be assessed for airway inflammation using fractional exhaled nitric oxide, and sputum analysis. These subjects will be observed taking their medication to determine if this reduces their level of airway inflammation. Prescription records will be used to ascertain if this test distinguishes those who are non-adherent with their treatment from those adults who have severe asthma.

Identifying patients who are non-adherent to treatment will allow an appropriate change in management and enable alternative strategies to be developed to tackle non-adherence in this population. Distinguishing patients who are adherent to treatment but have therapy resistant disease would significantly improve treatment effectiveness in this group by allowing these patients to be suitably targeted with expensive novel therapies such as Omalizumab.


Condition Intervention
Asthma
Drug: Budesonide (directly observed)

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Health Services Research
Official Title: The Use of Fractional Exhaled Nitric Oxide (FeNO) and Induced Sputum in the Identification of Non-adherence in Difficult to Control Asthma

Resource links provided by NLM:


Further study details as provided by Belfast Health and Social Care Trust:

Primary Outcome Measures:
  • Fractional exhaled nitric oxide [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    The change in fractional exhaled nitric oxide after 7 days of directly observed inhaled corticosteroids and comparison of between group differences


Secondary Outcome Measures:
  • Sputum eosinophil count [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    Change in sputum eosinophil count

  • Asthma Control Questionnaire Score [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    Change in the Juniper Asthma Control Questionnaire Score following directly observed inhaled corticosteroid therapy


Enrollment: 40
Study Start Date: October 2008
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Non-adherent Drug: Budesonide (directly observed)
Budesonide 1600 micrograms daily directly observed for 7 days
Other Name: Pulmicort
Adherent Drug: Budesonide (directly observed)
Budesonide 1600 micrograms daily directly observed for 7 days
Other Name: Pulmicort

Detailed Description:

Hypothesis:

In a difficult asthma population, a significant reduction in fractional exhaled nitric oxide (FeNO) or sputum eosinophils after a directly observed inhaled steroid challenge will distinguish non-adherent subjects from subjects with refractory asthma.

Study Design The study will consist of two phases. The development phase will identify the response of FeNO / sputum eosinophils after directly observed inhaled steroid challenge, in non-adherent subjects and define cut-off values for a positive and negative test and identify the optimum length of steroid challenge. The validation phase will trial and validate the test in a 'real life' clinical setting.

Phase 1 - Development Phase

During this phase, two groups will be studied:

  • Non-adherent group - subjects with < 50% prescription filling in previous 6 months and persistently high FeNO.
  • Adherent group - subjects with high prescription filling (> 75%) and persistently high FeNO.

On Day 0, subjects will have a FeNO measurement will be repeated, perform induced sputum and complete an asthma control questionnaire. After inhaler technique is deemed satisfactory, all subjects will be directly observed taking 1600μg of inhaled budesonide via Turbohaler (or bioequivalent dose of Budesonide via MDI / spacer). On the next 6 days, the investigator will visit the subjects and perform FeNO measurements, followed by directly observed inhalation of 1600 μg of inhaled budesonide via appropriate inhaler device.

On Day 7, subjects will undergo FeNO measurement, induced sputum and an asthma control questionnaire. Following who fail to suppress their FeNO level will receive an intramuscular injection of Triamcinolone 80mg and will be asked to attend the clinic weekly for 4 weeks for measurement of FeNO levels and induced sputum.

Based on results the investigators will:

  1. Identify if there is a clearly different response in FeNO / sputum eosinophils in adherent and non-adherent groups during a 7 day treatment period, with observed high dose inhaled steroid therapy, which will define the clinical utility of the technique.
  2. Define cut-off values for a positive test (i.e. which is consistent with non-adherence) and a negative test which should mean adherence and consequently refractory asthma.
  3. Define the optimal length of steroid challenge for the validation phase based on clinical ease of use and differentiation precision.

Phase 2 - Validation in a real life Clinical Setting

Having defined the test, the validation phase will involve prospectively recruited subjects, who have a raised FeNO but the investigators will not have access to their prescription records at this stage. These subjects will undergo the steroid challenge defined above and will be deemed adherent or non-adherent. After the steroid challenge has been performed, this will be compared to prescription records and patient confrontation to identify if the challenge identifies non-adherence.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Phase 1 Inclusion Criteria:

  • Subjects with difficult to control asthma
  • FeNO > 45 ppb at a flow rate of 50 ml/sec on 2 sequential occasions at clinical review
  • Non-adherent group: < 50% prescription filling of inhaled corticosteroid therapy in the previous 6 months
  • Adherent group: > 75% prescription filling of inhaled corticosteroid therapy in the previous 6 months

Phase 1 Exclusion Criteria:

  • Current smoker
  • Pregnancy
  • Other significant respiratory disease

Phase 2 Inclusion Criteria:

  • Subjects with difficult to control asthma
  • FeNO > 45 ppb at a flow rate of 50 ml/sec on 2 sequential occasions at clinical review

Phase 2 Exclusion Criteria:

  • Current smoker
  • Pregnancy
  • Other significant respiratory disease
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01219036

Locations
United Kingdom
Regional Respiratory Centre, Belfast City Hospital
Belfast, United Kingdom, BT9 7AB
Sponsors and Collaborators
Liam Heaney
Queen's University, Belfast
Asthma UK
Northern Ireland Chest Heart & Stroke
Investigators
Principal Investigator: Liam G Heaney, MD Belfast Health & Social Care Trust
  More Information

No publications provided by Belfast Health and Social Care Trust

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Liam Heaney, Consultant Physician, Belfast Health and Social Care Trust
ClinicalTrials.gov Identifier: NCT01219036     History of Changes
Other Study ID Numbers: 07094LH-A, 08/031, 2008 114
Study First Received: October 12, 2010
Last Updated: February 1, 2012
Health Authority: United Kingdom: Research Ethics Committee

Keywords provided by Belfast Health and Social Care Trust:
Asthma
Non-adherence
Fractional exhaled nitric oxide

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Nitric Oxide
Budesonide
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Endothelium-Dependent Relaxing Factors
Vasodilator Agents
Cardiovascular Agents
Gasotransmitters
Protective Agents
Anti-Inflammatory Agents
Glucocorticoids

ClinicalTrials.gov processed this record on September 15, 2014