AsthmaPhase 4NSRSNCT02294279
The Evaluation of FeNO for Predicting Response to ICS in Subjects With Non-specific Respiratory Symptoms
A Phase 4 study testing Qvar (100 mcg) in people with Asthma, run by Research in Real-Life Ltd at 1 site in United Kingdom.
Trial summary
Nitric Oxide is recognized as a biological marker for many chronic airway diseases. It has been standardised for clinical use indicating airway inflammation. In clinical practice, FeNO can aid confirmation of an asthma diagnosis and can indicate the degree of steroid-responsiveness. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Asthma
- What is being tested?
- Qvar (100 mcg)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 360 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- May 2014to Aug 2016
- Phase
- Phase 4
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent is obtained before conducting any study-related procedures
- The patient is a man or woman aged 18 to 80 years as of the screening visit
- The patient is experiencing non-specific respiratory symptoms defined as follows: Cough and/or wheeze and/or chronic dyspnoea for ≥ 6 weeks prior to visit 1
- Patients displaying an FEV1< 90% predicted at visit 1, will also need to show a reversibility to a short-acting beta-agonist of < 20% at visit 1 or within the previous year
- Women of childbearing potential (post-menarche or less than 2 years post-menopausal or not surgically sterile) must be willing to commit to using a medically accepted method of contraception for the duration of the study. Accepted methods of contraception include: intrauterine devices (IUD), systemic contraception e.g. steroidal contraceptives (oral, implanted transdermal or injected), barrier methods with spermicide, and partner vasectomy
Who cannot join
- The patient has ever been diagnosed with asthma as evidenced by the UK quality outcome framework approved Read code as well as a reversibility of ≥ 20% predicted
- The patient has received oral, inhaled or systemic corticosteroids, a leukotriene modifier or long-acting-beta-agonist within four weeks prior to visit 1. All therapy and treatment other than those outlined are permitted during the study
- The patient has a significant chronic respiratory disorder other than asthma, e.g. COPD (fixed obstruction, post-bronchodilator) cystic fibrosis, severe and untreated bronchiectasis or interstitial lung disease
- The patient has a significant medical condition that would make it unlikely for the patient to complete the study
- The patient has a known significant risk factor for cough or wheeze, including but not limited to: taking an ACE inhibitor, severe untreated rhinitis, or significant gastroesophageal reflux disease
- The patient is asymptomatic (ACQ < 1) after the initial 2-week assessment
- The patient has had a respiratory tract infection as judged clinically, within four weeks prior to visit 1, or displays an acute respiratory tract infection at the time of the study
- The patient is a pregnant woman or intends to get pregnant (Any woman becoming pregnant during the study will be withdrawn from the study)
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Research in Real Life Ltd
Oakington, Cambridgeshire, CB24 3BA
About this study
Official title: The Evaluation of FeNO for Predicting Response to an Inhaled Corticosteroid in Subjects With Non-specific Respiratory Symptoms
Nitric Oxide is recognized as a biological marker for many chronic airway diseases. It has been standardised for clinical use indicating airway inflammation.
In clinical practice, FeNO can aid confirmation of an asthma diagnosis and can indicate the degree of steroid-responsiveness. This can help guide physician decisions on the initiation of inhaled corticosteroid (ICS) therapy, or adjustment of ICS therapy.
Read more
Therefore, FeNO measurement could be particularly useful to confirm an asthma diagnosis in patients with non-specific respiratory symptoms (≥ 6 weeks of cough and/or wheezing and/or chronic dyspnoea) and to assess how likely they are to benefit from corticosteroid treatment.
This study will assess the suitability of FeNO to predict ICS responsiveness in patients with non-specific respiratory symptoms.
Additionally, we would like to determine the suitability of FeNO as a diagnostic tool for asthma in comparison to conventional predictors, e.g. spirometry.
Read the detailed description
Randomised, double-blind, placebo-controlled trial with planned enrolment of 264 patients from the UK and Singapore. Eligible patients are 18-80 years old with ≥6 weeks' duration of non-specific respiratory symptoms defined as cough and/or wheeze and/or dyspnoea. Patients with FEV1 <90% predicted at visit 1 must show reversibility of <20% at visit 1 or within the prior year. Key exclusion criteria are prior diagnosis of asthma; evidence of concomitant chronic respiratory disease, respiratory tract infection; or known significant risk factor for cough or wheeze.
Baseline assessments will include spirometry (FEV1, forced vital capacity) and FeNO measurement. Patients will be provided with a peak flow meter for twice daily measurement throughout the study. At 2 weeks, a clinical assessment and spirometry will be performed to confirm eligibility, and patients will complete four validated questionnaires to assess quality of life, asthma control, and asthma symptoms, including a visual analog scale for bother from asthma symptoms. Eligible patients will then be stratified by baseline FeNO level (normal ≤25, intermediate >25 to ≤50, or high >50 ppb); each group will be randomised to receive beclometasone 400 mcg daily or placebo for 6 weeks. An optional blood sample will be collected from consenting patients to assess blood eosinophils.
At visit 3, final assessments will include spirometry, FeNO measurement, and all questionnaires. Interaction analysis will be used to determine whether a differential effect exists in response to ICS between FeNO groups.
- Conditions
- Asthma
- Being tested
- Qvar (100 mcg)
- Keywords
- cough, wheeze, dyspnoea
- Medical subject headings
- Asthma, Cough, Respiratory Sounds, Dyspnea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Qvar (100 mcg)Drug
Also called Beclomethasone diproprionate
2 puffs twice daily; 400 mcg daily over 4 weeks treatment period
| Study group | Role | What they receive |
|---|---|---|
| Active | Experimental | 4 weeks of corticosteroid treatment with QVAR (100mcg), 400 mcg daily; two puffs twice daily Receives: Drug: Qvar (100 mcg) |
| Placebo | No intervention | Blinded placebo inhaler |
What is being measured
The primary outcome is the main question the study is designed to answer.
Asthma Control Questionnaire (ACQ)
The Asthma control questionnaire (ACQ) is a seven question (i.e. the top scoring 5 symptoms, daily rescue bronchodilator use and FEV1% pred.), validated tool for assessing asthma control. Patients are asked to recall how their asthma has been during the last 7 days and to evaluate their asthma against 5 symptom questions and a rescue bronchodilator use question on a 6-point scale (0 = no impairment, 6 = maximum impairment). In addition, the research nurse will grade the FEV1 % predicted on a 6 point scale (0 to 6). The questions are equally weighted and ACQ7 score is the mean of the 7 questions, generating a value between 0 (totally controlled) and 6 (severely uncontrolled).
Measured: Baseline and 4 weeks
Secondary outcomes (6)
EuroQol 5 dimension questionnaire
The EQ-5D-3L questionnaire is a validated instrument that derives a person's health profile. The EQ-5D-3L consists of two parts. The first one is the EQ descriptive system which comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The respondent is asked to indicate their health state by ticking the most appropriate statement (no problems to extreme problems). The second part is the EQ visual analog scale (EQ VAS). It records the respondent's self-rated health on a 20 cm vertical,visual analogue scale with endpoints labelled "the best health you can imagine" and "the worst health you can imagine".
Measured: Baseline and 4 weeks
Visual Analogue Scale test (VAS) and cough Visual analogue scale test
Patients rate their symptom/cough severity by placing a mark on a line to indicate symptom severity.
Measured: Baseline and 4 weeks
Spirometry (PEF, FEV1, FVC, FEV1/FVC)
Spirometry will be conducted to obtain an objective measure of the patient's lung function
Measured: 3 days
Eosinophil analysis
A blood test will be taken from consenting patients to assess the eosinophil level as marker for inflammation.
Measured: 1 day
Peak expiratory flow (PEF diary)
Peak expiratory flow will be measured using a portable peak flow meter.
Measured: From visit 1 till 6 weeks follow-up (2 recordings per day over 6 weeks)
Global Evaluation of Treatment Effectiveness Scale (GETE)
Clinical judgment on whether the treatment was successful on a 5-point scale
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2014 (estimated)
- Study startMay 2014
- Primary completionAug 2016
- Study completionAug 2016
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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 360 participants (actual)
Sponsor and investigators
- Lead sponsor
- Research in Real-Life Ltd
- Sponsor type
- Research network
- Collaborators
- Aerocrine AB
- Responsible party
- Sponsor
- Investigators
- David Price, Prof, Study director, Research in Real Life
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02294279
- Sponsor's protocol ID
- OR01013
- Acronym
- NSRS
- Status last verified
- Apr 2017
- First submitted
- 14 Nov 2014
- Last updated
- 25 Apr 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided: Principal investigator has not made a decision regarding a plan to share data at this point in time.
Publications
Price DB, Buhl R, Chan A, Freeman D, Gardener E, Godley C, Gruffydd-Jones K, McGarvey L, Ohta K, Ryan D, Syk J, Tan NC, Tan T, Thomas M, Yang S, Konduru PR, Ngantcha M, d'Alcontres MS, Lapperre TS. Fractional exhaled nitric oxide as a predictor of response to inhaled corticosteroids in patients with non-specific respiratory symptoms and insignificant bronchodilator reversibility: a randomised controlled trial. Lancet Respir Med. 2018 Jan;6(1):29-39. doi: 10.1016/S2213-2600(17)30424-1. Epub 2017 Nov 3.
PubMed 29108938
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Evaluation of FeNO for Predicting Response to an Inhaled Corticosteroid in Subjects With Non-specific Respiratory Symptoms
- ClinicalTrials.gov ID
- NCT02294279
- Acronym / sponsor ID
- NSRS / OR01013
- Conditions
- Asthma
- Keywords
- cough, wheeze, dyspnoea
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 360 participants (actual)
- Lead sponsor
- Research in Real-Life LtdResearch network
- Collaborators
- Aerocrine AB
- Study start
- May 2014 (actual)
- Primary completion
- Aug 2016 (actual)
- Study completion
- Aug 2016 (actual)
- First posted
- 19 Nov 2014 (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.
Nitric Oxide is recognized as a biological marker for many chronic airway diseases. It has been standardised for clinical use indicating airway inflammation.
In clinical practice, FeNO can aid confirmation of an asthma diagnosis and can indicate the degree of steroid-responsiveness. This can help guide physician decisions on the initiation of inhaled corticosteroid (ICS) therapy, or adjustment of ICS therapy.
Therefore, FeNO measurement could be particularly useful to confirm an asthma diagnosis in patients with non-specific respiratory symptoms (≥ 6 weeks of cough and/or wheezing and/or chronic dyspnoea) and to assess how likely they are to benefit from corticosteroid treatment.
This study will assess the suitability of FeNO to predict ICS responsiveness in patients with non-specific respiratory symptoms.
Additionally, we would like to determine the suitability of FeNO as a diagnostic tool for asthma in comparison to conventional predictors, e.g. spirometry.
Detailed description
Randomised, double-blind, placebo-controlled trial with planned enrolment of 264 patients from the UK and Singapore. Eligible patients are 18-80 years old with ≥6 weeks' duration of non-specific respiratory symptoms defined as cough and/or wheeze and/or dyspnoea. Patients with FEV1 <90% predicted at visit 1 must show reversibility of <20% at visit 1 or within the prior year. Key exclusion criteria are prior diagnosis of asthma; evidence of concomitant chronic respiratory disease, respiratory tract infection; or known significant risk factor for cough or wheeze.
Baseline assessments will include spirometry (FEV1, forced vital capacity) and FeNO measurement. Patients will be provided with a peak flow meter for twice daily measurement throughout the study. At 2 weeks, a clinical assessment and spirometry will be performed to confirm eligibility, and patients will complete four validated questionnaires to assess quality of life, asthma control, and asthma symptoms, including a visual analog scale for bother from asthma symptoms. Eligible patients will then be stratified by baseline FeNO level (normal ≤25, intermediate >25 to ≤50, or high >50 ppb); each group will be randomised to receive beclometasone 400 mcg daily or placebo for 6 weeks. An optional blood sample will be collected from consenting patients to assess blood eosinophils.
At visit 3, final assessments will include spirometry, FeNO measurement, and all questionnaires. Interaction analysis will be used to determine whether a differential effect exists in response to ICS between FeNO groups.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active | Experimental | Drug: Qvar (100 mcg)4 weeks of corticosteroid treatment with QVAR (100mcg), 400 mcg daily; two puffs twice daily |
| Placebo | No intervention | –Blinded placebo inhaler |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Written informed consent is obtained before conducting any study-related procedures
- The patient is a man or woman aged 18 to 80 years as of the screening visit
- The patient is experiencing non-specific respiratory symptoms defined as follows: Cough and/or wheeze and/or chronic dyspnoea for ≥ 6 weeks prior to visit 1
- Patients displaying an FEV1< 90% predicted at visit 1, will also need to show a reversibility to a short-acting beta-agonist of < 20% at visit 1 or within the previous year
- Women of childbearing potential (post-menarche or less than 2 years post-menopausal or not surgically sterile) must be willing to commit to using a medically accepted method of contraception for the duration of the study. Accepted methods of contraception include: intrauterine devices (IUD), systemic contraception e.g. steroidal contraceptives (oral, implanted transdermal or injected), barrier methods with spermicide, and partner vasectomy
Key exclusion criteria (8 listed)
- The patient has ever been diagnosed with asthma as evidenced by the UK quality outcome framework approved Read code as well as a reversibility of ≥ 20% predicted
- The patient has received oral, inhaled or systemic corticosteroids, a leukotriene modifier or long-acting-beta-agonist within four weeks prior to visit 1. All therapy and treatment other than those outlined are permitted during the study
- The patient has a significant chronic respiratory disorder other than asthma, e.g. COPD (fixed obstruction, post-bronchodilator) cystic fibrosis, severe and untreated bronchiectasis or interstitial lung disease
- The patient has a significant medical condition that would make it unlikely for the patient to complete the study
- The patient has a known significant risk factor for cough or wheeze, including but not limited to: taking an ACE inhibitor, severe untreated rhinitis, or significant gastroesophageal reflux disease
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 |
|---|---|---|
| Qvar (100 mcg)Also: Beclomethasone diproprionate2 puffs twice daily; 400 mcg daily over 4 weeks treatment period | Drug | Active |
Primary outcome
Asthma Control Questionnaire (ACQ)
Time frame: Baseline and 4 weeks
The Asthma control questionnaire (ACQ) is a seven question (i.e. the top scoring 5 symptoms, daily rescue bronchodilator use and FEV1% pred.), validated tool for assessing asthma control. Patients are asked to recall how their asthma has been during the last 7 days and to evaluate their asthma against 5 symptom questions and a rescue bronchodilator use question on a 6-point scale (0 = no impairment, 6 = maximum impairment). In addition, the research nurse will grade the FEV1 % predicted on a 6 point scale (0 to 6). The questions are equally weighted and ACQ7 score is the mean of the 7 questions, generating a value between 0 (totally controlled) and 6 (severely uncontrolled).
6 secondary outcomes
EuroQol 5 dimension questionnaire
Time frame: Baseline and 4 weeks
Visual Analogue Scale test (VAS) and cough Visual analogue scale test
Time frame: Baseline and 4 weeks
Spirometry (PEF, FEV1, FVC, FEV1/FVC)
Time frame: 3 days
Eosinophil analysis
Time frame: 1 day
Peak expiratory flow (PEF diary)
Time frame: From visit 1 till 6 weeks follow-up (2 recordings per day over 6 weeks)
Global Evaluation of Treatment Effectiveness Scale (GETE)
Time frame: 1 day
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 25 Apr 2017.
- Derived from this study: PubMed 29108938Price DB, Buhl R, Chan A, Freeman D, Gardener E, Godley C, Gruffydd-Jones K, McGarvey L, Ohta K, Ryan D, Syk J, Tan NC, Tan T, Thomas M, Yang S, Konduru PR, Ngantcha M, d'Alcontres MS, Lapperre TS. Fractional exhaled nitric oxide as a predictor of response to inhaled corticosteroids in patients with non-specific respiratory symptoms and insignificant bronchodilator reversibility: a randomised controlled trial. Lancet Respir Med. 2018 Jan;6(1):29-39. doi: 10.1016/S2213-2600(17)30424-1. Epub 2017 Nov 3.
- Individual participant dataSharing planned: Undecided. Principal investigator has not made a decision regarding a plan to share data at this point in time.
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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.
David Price, Prof study director
Research in Real Life
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Qvar (100 mcg) in people with Asthma, run by Research in Real-Life Ltd 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 8 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 25 Apr 2017. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Asthma Control Questionnaire (ACQ) (time frame: Baseline and 4 weeks). 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 NCT02294279, 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 25 Apr 2017.