AsthmaNCT01219036
The Use of Fractional Exhaled Nitric Oxide in the Identification of Non-adherence in Difficult Asthma
A study testing Budesonide (directly observed) in people with Asthma, run by Liam Heaney at 1 site in United Kingdom.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Asthma
- What is being tested?
- Budesonide (directly observed)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Oct 2008to Jul 2011
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Regional Respiratory Centre, Belfast City Hospital
Belfast, BT9 7AB
About this study
Official title: 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.
Read the 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:
- 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.
- 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.
- 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.
- Conditions
- Asthma
- Being tested
- Budesonide (directly observed)
- Keywords
- Asthma, Non-adherence, Fractional exhaled nitric oxide
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Budesonide (directly observed)Drug
Also called Pulmicort
Budesonide 1600 micrograms daily directly observed for 7 days
| Study group | Role | What they receive |
|---|---|---|
| Non-adherent | Other | Not described Receives: Drug: Budesonide (directly observed) |
| Adherent | Other | Not described Receives: Drug: Budesonide (directly observed) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fractional exhaled nitric oxide
The change in fractional exhaled nitric oxide after 7 days of directly observed inhaled corticosteroids and comparison of between group differences
Measured: 7 days
Secondary outcomes (2)
Sputum eosinophil count
Change in sputum eosinophil count
Measured: 7 days
Asthma Control Questionnaire Score
Change in the Juniper Asthma Control Questionnaire Score following directly observed inhaled corticosteroid therapy
Measured: 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2010 (estimated)
- Study startOct 2008
- Primary completionJul 2011
- Study completionJul 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AsthmaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Health services research
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Liam Heaney
- Sponsor type
- University, hospital or other
- Collaborators
- Queen's University, Belfast, Asthma UK, Northern Ireland Chest Heart and Stroke
- Responsible party
- Sponsor-investigator, Liam Heaney, Belfast Health and Social Care Trust
- Investigators
- Liam G Heaney, MD, Principal investigator, Belfast Health & Social Care Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01219036
- Sponsor's protocol ID
- 07094LH-A
- Other IDs
- 08/031, 2008 114
- Status last verified
- Feb 2012
- First submitted
- 12 Oct 2010
- Last updated
- 3 Feb 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
McNicholl DM, Stevenson M, McGarvey LP, Heaney LG. The utility of fractional exhaled nitric oxide suppression in the identification of nonadherence in difficult asthma. Am J Respir Crit Care Med. 2012 Dec 1;186(11):1102-8. doi: 10.1164/rccm.201204-0587OC. Epub 2012 Sep 28.
PubMed 23024023
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Use of Fractional Exhaled Nitric Oxide (FeNO) and Induced Sputum in the Identification of Non-adherence in Difficult to Control Asthma
- ClinicalTrials.gov ID
- NCT01219036
- Acronym / sponsor ID
- 07094LH-A
- Conditions
- Asthma
- Keywords
- Asthma, Non-adherence, Fractional exhaled nitric oxide
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Liam HeaneyUniversity, hospital or other
- Collaborators
- Queen's University, Belfast, Asthma UK, Northern Ireland Chest Heart and Stroke
- Study start
- Oct 2008
- Primary completion
- Jul 2011 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 13 Oct 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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:
- 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.
- 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.
- 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 design
- Primary purpose
- Health services research
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Non-adherent | Other | Drug: Budesonide (directly observed) |
| Adherent | Other | Drug: Budesonide (directly observed) |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Budesonide (directly observed)Also: PulmicortBudesonide 1600 micrograms daily directly observed for 7 days | Drug | Adherent, Non-adherent |
Primary outcome
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
2 secondary outcomes
Sputum eosinophil count
Time frame: 7 days
Asthma Control Questionnaire Score
Time frame: 7 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Feb 2012.
- Derived from this study: PubMed 23024023McNicholl DM, Stevenson M, McGarvey LP, Heaney LG. The utility of fractional exhaled nitric oxide suppression in the identification of nonadherence in difficult asthma. Am J Respir Crit Care Med. 2012 Dec 1;186(11):1102-8. doi: 10.1164/rccm.201204-0587OC. Epub 2012 Sep 28.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Liam G Heaney, MD principal investigator
Belfast Health & Social Care Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Budesonide (directly observed) in people with Asthma, run by Liam Heaney at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Feb 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fractional exhaled nitric oxide (time frame: 7 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01219036, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Feb 2012.