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

February 1, 2012 updated by: Liam Heaney

The Use of Fractional Exhaled Nitric Oxide (FeNO) and Induced Sputum in the Identification of Non-adherence in Difficult to Control Asthma

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • Belfast, United Kingdom, BT9 7AB
        • Regional Respiratory Centre, Belfast City Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Health Services Research
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Non-adherent
Drug: Budesonide (directly observed)
Budesonide 1600 micrograms daily directly observed for 7 days
Other Names:
  • Pulmicort
Other: Adherent
Drug: Budesonide (directly observed)
Budesonide 1600 micrograms daily directly observed for 7 days
Other Names:
  • Pulmicort

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Fractional exhaled nitric oxide
Time Frame: 7 days
The change in fractional exhaled nitric oxide after 7 days of directly observed inhaled corticosteroids and comparison of between group differences
7 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sputum eosinophil count
Time Frame: 7 days
Change in sputum eosinophil count
7 days
Asthma Control Questionnaire Score
Time Frame: 7 days
Change in the Juniper Asthma Control Questionnaire Score following directly observed inhaled corticosteroid therapy
7 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Liam Heaney

Collaborators

Queen's University, Belfast
Northern Ireland Chest Heart and Stroke
Asthma UK

Investigators

  • Principal Investigator: Liam G Heaney, MD, Belfast Health & Social Care Trust

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2008

Primary Completion (Actual)

July 1, 2011

Study Completion (Actual)

July 1, 2011

Study Registration Dates

First Submitted

October 12, 2010

First Submitted That Met QC Criteria

October 12, 2010

First Posted (Estimate)

October 13, 2010

Study Record Updates

Last Update Posted (Estimate)

February 3, 2012

Last Update Submitted That Met QC Criteria

February 1, 2012

Last Verified

February 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 07094LH-A
  • 08/031 (Other Grant/Funding Number: Asthma UK)
  • 2008 114 (Other Grant/Funding Number: Northern Ireland Chest Heart & Stroke)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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