AsthmaPCRNCT01308411
Predicting Steroid Response Using Exhaled Nitric Oxide
A study testing 50% step down reduction in inhaled corticosteroid dose in people with Asthma, run by University of Nottingham at 1 site in United Kingdom.
Trial summary
Asthma affects 6% of the UK population and costs the NHS 1 billion pounds per year. £473 million alone is spent on inhaled steroid treatment which is designed to reduce inflammation in the breathing tubes. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Asthma
- What is being tested?
- 50% step down reduction in inhaled corticosteroid dose
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 191 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Nov 2010to Sep 2013
- 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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients (18-75 years of age)
- diagnosis of asthma
- step 2, 3 or 4 on the BTS asthma guidelines.
- Well controlled asthma and good lung function, as defined as a Juniper asthma control score of < 1.5.
- Not oral steroids in the last 3 months.
Who cannot join
- Incapable of giving informed consent.
- Poor treatment concordance.
- Pregnant women.
- Extensive co-morbidity.
- Previous admission to ITU with asthma.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Leicester Glenfield Hospital
Leicester, Leicestershire, LE60DA
About this study
Official title: Using Exhaled Nitric Oxide to Step Down Inhaled Corticosteroid Therapy in Asthma
Asthma affects 6% of the UK population and costs the NHS 1 billion pounds per year. £473 million alone is spent on inhaled steroid treatment which is designed to reduce inflammation in the breathing tubes.
Unfortunately knowing whether a patient is on just the right amount of steroid treatment is difficult, as asthma is a variable disease and the measures currently used to decide on increasing or decreasing steroid treatment bare little resemblance to the actual amount of inflammation present. Doctors may not reduce treatment as swiftly as necessary if a patient's asthma is well controlled because of concern over asthma attacks; this can result in potential over treatment with inhaled steroids. Although steroid treatment is safe, side effects can occur, and costs are large, so a strategy helping avoid over treatment would be beneficial both to patients and to the NHS.
As the investigators can more accurately measure airway inflammation present in the breathing tubes, using a chemical called nitric oxide present in a patient's breath, the investigators might be able to more accurately predict which patients could safely reduce their steroid treatment. Measuring nitric oxide is simple, and involves breathing into a special machine (similar to a roadside breathalyser). In this study the investigators will measure nitric oxide in patients with well controlled asthma, and reduce their asthma treatment by 50%. The investigators will then follow up the patients and remeasure their nitric oxide. At the end of the study the investigators will see if measurements of nitric oxide predicted which patients could safely step down their treatment. If successful this could help reduce the overall cost to the NHS of inhaled steroids and reduce steroid associated side effects.
Read the detailed description
The principal objective is to establish whether a baseline measurement of airway inflammation, as measured in exhaled breath, or a variation in this measurement over time, can predict which patients can safely step down their asthma treatment without experiencing a loss of asthma control.
This study is designed to show whether a policy utilising measurements of exhaled nitric oxide (present in the breath) in guiding asthma treatment will be feasible, and is worth testing in a future prospective study.
The secondary objectives are to establish if this approach is feasible, safe and cost effective, when compared to current clinical guidelines.
Asthma is defined by the presence of symptoms associated with variable airflow obstruction, airway inflammation and airway hyperresponsiveness. Inhaled corticosteroids are one of the most commonly used treatments in asthma, currently £473 million per year is spent on these medications alone in the UK. Guidelines recommend that treatment decisions are based on assessment of symptoms and airflow obstruction. However, as there is no clear relationship between symptom control, airflow obstruction and airway inflammation, there is a risk that patients can be over treated. In the U.K. 80% of patients with asthma are managed in primary care; assessment of airway inflammation is not applicable in this setting, and management relies on the assessment of peak flow and symptoms.
Recently the concentration of nitric oxide present in exhaled breath (FENO) has been evaluated as a tool for assessing asthma. FENO is elevated in patients with asthma, is reduced by treatment with inhaled corticosteroids(8) and correlates with airway inflammation measured using bronchial biopsies and induced sputum. It is particularly applicable for monitoring asthma in primary care as the test is easy to perform, provides an immediate result, and inexpensive portable monitors are now available. FENO appears to be a very specific, but not sensitive, marker of airway inflammation and using a low level of FENO to predict lack of treatable airway inflammation may be successful. Evidence from a study in children suggests that this strategy may be successful. However, most studies using FENO to guide ICS dose have not adopted this approach and have instead been randomised controlled trials using a step up/ down protocol whereby a high FENO leads to a step up in ICS dose, and a low FENO leads to a step down in dose. They have attempted to both reduce asthma exacerbations despite also trying to reduce steroid dose. These studies have not met their primary endpoints and have been reviewed in a Cochrane report. In the study by Shaw et al. a similar amount of ICS was used over the duration of the study in both the group managed by FENO and the control group; there was however a difference at the end of the study, with the FENO group using significantly less ICS. In the study by Smith et al. the daily dose of ICS was significantly lower at all time points, however the study results are not applicable as patients did not receive long acting β2 agonists, and the ICS dose in the control group was artificially inflated. These trials lend weight to the idea that utilising a step down approach to FENO and ICS may be successful. Importantly there was no significant difference in asthma exacerbation rates between control or treatment group in either study, suggesting that an approach utilising by FENO is inherently safe. Other studies support this supposition; one study suggested a close correlation between loss of asthma control and ICS reduction, and another study demonstrated that within 2 weeks of a reduction in ICS, FENO rises back to baseline, however exact cut off values for a simple step down strategy have never been sought, despite evidence that this would constitute the best approach.
Most patients are at step 2-3 of the asthma guidelines, receiving ICS doses of between 200-800mcgs, and are managed in primary care; guidelines for a 50% reduction in ICS at 3 months are based on sparse evidence. If a low FENO can identify patients who can step down their ICS treatment without a risk of worsening asthma, a strategy using FENO is likely to be adopted into current guidelines.
- Conditions
- Asthma
- Being tested
- 50% step down reduction in inhaled corticosteroid dose
- Keywords
- Asthma, Inhaled Corticosteroids, Exhaled Nitric oxide, Airways inflammation, Step down, Predicting response
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
50% step down reduction in inhaled corticosteroid doseOther
All participants will have their inhaled corticosteroid dose reduced by 50%
| Study group | Role | What they receive |
|---|---|---|
| 50% reduction in ICS dose | Experimental | All patients will reduce their inhaled corticosteroid dose by 50% Receives: Other: 50% step down reduction in inhaled corticosteroid dose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Whether a baseline measurement of airway inflammation, as measured in exhaled breath, or a variation in this measurement over time, can predict which patients can safely step down their asthma treatment without experiencing a loss of asthma control.
The main outcome is whether a low FENO value at baseline or visit four or visit five, or variability from baseline in FENO, predicts which participants can successfully step down ICS dose without provoking increasing asthma symptom
Measured: visit 4 and visit 5
Secondary outcomes (1)
The secondary objectives are to establish if this approach is feasible, safe and cost effective, when compared to current clinical guidelines.
The secondary outcome will be whether a rise in FENO from baseline predicted a clinically important drop in spirometry, methacholine PC20 or change in differential induced sputum cell counts
Measured: visit 2 and visit 5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2011 (estimated)
- Study startNov 2010
- Primary completionMar 2012
- Study completionSep 2013
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.
- More trials run by University of NottinghamThe sponsor's other registered studies.
- 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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 191 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Nottingham
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Dominick Shaw, Dr, Principal investigator, University of Nottingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01308411
- Sponsor's protocol ID
- 10010
- Acronym
- PCR
- Status last verified
- Jan 2014
- First submitted
- 28 May 2010
- Last updated
- 3 Feb 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Wilson E, McKeever T, Hargadon B, Hearson G, Anderson J, Hodgson D, Bailey H, Meakin G, Thomas M, Pavord ID, Harrison T, Shaw D. Exhaled nitric oxide and inhaled corticosteroid dose reduction in asthma: a cohort study. Eur Respir J. 2014 Dec;44(6):1705-7. doi: 10.1183/09031936.00093614. Epub 2014 Aug 19. No abstract available.
PubMed 25142486
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Using Exhaled Nitric Oxide to Step Down Inhaled Corticosteroid Therapy in Asthma
- ClinicalTrials.gov ID
- NCT01308411
- Acronym / sponsor ID
- PCR / 10010
- Conditions
- Asthma
- Keywords
- Asthma, Inhaled Corticosteroids, Exhaled Nitric oxide, Airways inflammation, Step down, Predicting response
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 191 participants (actual)
- Lead sponsor
- University of NottinghamUniversity, hospital or other
- Study start
- Nov 2010
- Primary completion
- Mar 2012 (actual)
- Study completion
- Sep 2013 (actual)
- First posted
- 4 Mar 2011 (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 affects 6% of the UK population and costs the NHS 1 billion pounds per year. £473 million alone is spent on inhaled steroid treatment which is designed to reduce inflammation in the breathing tubes.
Unfortunately knowing whether a patient is on just the right amount of steroid treatment is difficult, as asthma is a variable disease and the measures currently used to decide on increasing or decreasing steroid treatment bare little resemblance to the actual amount of inflammation present. Doctors may not reduce treatment as swiftly as necessary if a patient's asthma is well controlled because of concern over asthma attacks; this can result in potential over treatment with inhaled steroids. Although steroid treatment is safe, side effects can occur, and costs are large, so a strategy helping avoid over treatment would be beneficial both to patients and to the NHS.
As the investigators can more accurately measure airway inflammation present in the breathing tubes, using a chemical called nitric oxide present in a patient's breath, the investigators might be able to more accurately predict which patients could safely reduce their steroid treatment. Measuring nitric oxide is simple, and involves breathing into a special machine (similar to a roadside breathalyser). In this study the investigators will measure nitric oxide in patients with well controlled asthma, and reduce their asthma treatment by 50%. The investigators will then follow up the patients and remeasure their nitric oxide. At the end of the study the investigators will see if measurements of nitric oxide predicted which patients could safely step down their treatment. If successful this could help reduce the overall cost to the NHS of inhaled steroids and reduce steroid associated side effects.
Detailed description
The principal objective is to establish whether a baseline measurement of airway inflammation, as measured in exhaled breath, or a variation in this measurement over time, can predict which patients can safely step down their asthma treatment without experiencing a loss of asthma control.
This study is designed to show whether a policy utilising measurements of exhaled nitric oxide (present in the breath) in guiding asthma treatment will be feasible, and is worth testing in a future prospective study.
The secondary objectives are to establish if this approach is feasible, safe and cost effective, when compared to current clinical guidelines.
Asthma is defined by the presence of symptoms associated with variable airflow obstruction, airway inflammation and airway hyperresponsiveness. Inhaled corticosteroids are one of the most commonly used treatments in asthma, currently £473 million per year is spent on these medications alone in the UK. Guidelines recommend that treatment decisions are based on assessment of symptoms and airflow obstruction. However, as there is no clear relationship between symptom control, airflow obstruction and airway inflammation, there is a risk that patients can be over treated. In the U.K. 80% of patients with asthma are managed in primary care; assessment of airway inflammation is not applicable in this setting, and management relies on the assessment of peak flow and symptoms.
Recently the concentration of nitric oxide present in exhaled breath (FENO) has been evaluated as a tool for assessing asthma. FENO is elevated in patients with asthma, is reduced by treatment with inhaled corticosteroids(8) and correlates with airway inflammation measured using bronchial biopsies and induced sputum. It is particularly applicable for monitoring asthma in primary care as the test is easy to perform, provides an immediate result, and inexpensive portable monitors are now available. FENO appears to be a very specific, but not sensitive, marker of airway inflammation and using a low level of FENO to predict lack of treatable airway inflammation may be successful. Evidence from a study in children suggests that this strategy may be successful. However, most studies using FENO to guide ICS dose have not adopted this approach and have instead been randomised controlled trials using a step up/ down protocol whereby a high FENO leads to a step up in ICS dose, and a low FENO leads to a step down in dose. They have attempted to both reduce asthma exacerbations despite also trying to reduce steroid dose. These studies have not met their primary endpoints and have been reviewed in a Cochrane report. In the study by Shaw et al. a similar amount of ICS was used over the duration of the study in both the group managed by FENO and the control group; there was however a difference at the end of the study, with the FENO group using significantly less ICS. In the study by Smith et al. the daily dose of ICS was significantly lower at all time points, however the study results are not applicable as patients did not receive long acting β2 agonists, and the ICS dose in the control group was artificially inflated. These trials lend weight to the idea that utilising a step down approach to FENO and ICS may be successful. Importantly there was no significant difference in asthma exacerbation rates between control or treatment group in either study, suggesting that an approach utilising by FENO is inherently safe. Other studies support this supposition; one study suggested a close correlation between loss of asthma control and ICS reduction, and another study demonstrated that within 2 weeks of a reduction in ICS, FENO rises back to baseline, however exact cut off values for a simple step down strategy have never been sought, despite evidence that this would constitute the best approach.
Most patients are at step 2-3 of the asthma guidelines, receiving ICS doses of between 200-800mcgs, and are managed in primary care; guidelines for a 50% reduction in ICS at 3 months are based on sparse evidence. If a low FENO can identify patients who can step down their ICS treatment without a risk of worsening asthma, a strategy using FENO is likely to be adopted into current guidelines.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- Double blind (participant, care provider)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 50% reduction in ICS dose | Experimental | Other: 50% step down reduction in inhaled corticosteroid doseAll patients will reduce their inhaled corticosteroid dose by 50% |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Adult patients (18-75 years of age)
- diagnosis of asthma
- step 2, 3 or 4 on the BTS asthma guidelines.
- Well controlled asthma and good lung function, as defined as a Juniper asthma control score of < 1.5.
- Not oral steroids in the last 3 months.
Key exclusion criteria (5 listed)
- Incapable of giving informed consent.
- Poor treatment concordance.
- Pregnant women.
- Extensive co-morbidity.
- Previous admission to ITU with asthma.
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 |
|---|---|---|
| 50% step down reduction in inhaled corticosteroid doseAll participants will have their inhaled corticosteroid dose reduced by 50% | Other | 50% reduction in ICS dose |
Primary outcome
Whether a baseline measurement of airway inflammation, as measured in exhaled breath, or a variation in this measurement over time, can predict which patients can safely step down their asthma treatment without experiencing a loss of asthma control.
Time frame: visit 4 and visit 5
The main outcome is whether a low FENO value at baseline or visit four or visit five, or variability from baseline in FENO, predicts which participants can successfully step down ICS dose without provoking increasing asthma symptom
1 secondary outcome
The secondary objectives are to establish if this approach is feasible, safe and cost effective, when compared to current clinical guidelines.
Time frame: visit 2 and visit 5
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 2014.
- Derived from this study: PubMed 25142486Wilson E, McKeever T, Hargadon B, Hearson G, Anderson J, Hodgson D, Bailey H, Meakin G, Thomas M, Pavord ID, Harrison T, Shaw D. Exhaled nitric oxide and inhaled corticosteroid dose reduction in asthma: a cohort study. Eur Respir J. 2014 Dec;44(6):1705-7. doi: 10.1183/09031936.00093614. Epub 2014 Aug 19. No abstract available.
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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.
Dominick Shaw, Dr principal investigator
University of Nottingham
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing 50% step down reduction in inhaled corticosteroid dose in people with Asthma, run by University of Nottingham 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?
The sponsor lists 5 inclusion and 5 exclusion criteria. 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 2014. 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?
Whether a baseline measurement of airway inflammation, as measured in exhaled breath, or a variation in this measurement over time, can predict which patients can safely step down their asthma treatment without experiencing a loss of asthma control. (time frame: visit 4 and visit 5). 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 NCT01308411, 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 2014.