Back to results

The Evaluation of FeNO for Predicting Response to ICS in Subjects With Non-specific Respiratory Symptoms (NSRS)

Primary Purpose

Asthma

Status

Completed

Phase

Phase 4

Locations

United Kingdom

Study Type

Interventional

Intervention

Qvar (100 mcg)

About this trial

This is an interventional treatment trial for Asthma focused on measuring cough, wheeze, dyspnoea

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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)

Sites / Locations

Research in Real Life Ltd

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Active

Placebo

Arm Description

4 weeks of corticosteroid treatment with QVAR (100mcg), 400 mcg daily; two puffs twice daily

Blinded placebo inhaler

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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".

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.

Spirometry (PEF, FEV1, FVC, FEV1/FVC)

Spirometry will be conducted to obtain an objective measure of the patient's lung function

Eosinophil analysis

A blood test will be taken from consenting patients to assess the eosinophil level as marker for inflammation.

Peak expiratory flow (PEF diary)

Peak expiratory flow will be measured using a portable peak flow meter.

Global Evaluation of Treatment Effectiveness Scale (GETE)

Clinical judgment on whether the treatment was successful on a 5-point scale

Full Information

NCT ID

NCT02294279

First Posted

November 14, 2014

Last Updated

April 24, 2017

Sponsor

Research in Real-Life Ltd

Collaborators

Aerocrine AB

1. Study Identification

Unique Protocol Identification Number

NCT02294279

Brief Title

The Evaluation of FeNO for Predicting Response to ICS in Subjects With Non-specific Respiratory Symptoms

Acronym

NSRS

Official Title

The Evaluation of FeNO for Predicting Response to an Inhaled Corticosteroid in Subjects With Non-specific Respiratory Symptoms

Study Type

Interventional

2. Study Status

Record Verification Date

April 2017

Overall Recruitment Status

Completed

Study Start Date

May 2014 (Actual)

Primary Completion Date

August 2016 (Actual)

Study Completion Date

August 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Research in Real-Life Ltd

Collaborators

Aerocrine AB

4. Oversight

Data Monitoring Committee

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Asthma

Keywords

cough, wheeze, dyspnoea

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

360 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Active

Arm Type

Experimental

Arm Description

4 weeks of corticosteroid treatment with QVAR (100mcg), 400 mcg daily; two puffs twice daily

Arm Title

Placebo

Arm Type

No Intervention

Arm Description

Blinded placebo inhaler

Intervention Type

Drug

Intervention Name(s)

Qvar (100 mcg)

Other Intervention Name(s)

Beclomethasone diproprionate

Intervention Description

2 puffs twice daily; 400 mcg daily over 4 weeks treatment period

Primary Outcome Measure Information:

Title

Asthma Control Questionnaire (ACQ)

Description

Time Frame

Baseline and 4 weeks

Secondary Outcome Measure Information:

Title

EuroQol 5 dimension questionnaire

Description

Time Frame

Baseline and 4 weeks

Title

Visual Analogue Scale test (VAS) and cough Visual analogue scale test

Description

Patients rate their symptom/cough severity by placing a mark on a line to indicate symptom severity.

Time Frame

Baseline and 4 weeks

Title

Spirometry (PEF, FEV1, FVC, FEV1/FVC)

Description

Spirometry will be conducted to obtain an objective measure of the patient's lung function

Time Frame

3 days

Title

Eosinophil analysis

Description

A blood test will be taken from consenting patients to assess the eosinophil level as marker for inflammation.

Time Frame

1 day

Title

Peak expiratory flow (PEF diary)

Description

Peak expiratory flow will be measured using a portable peak flow meter.

Time Frame

From visit 1 till 6 weeks follow-up (2 recordings per day over 6 weeks)

Title

Global Evaluation of Treatment Effectiveness Scale (GETE)

Description

Clinical judgment on whether the treatment was successful on a 5-point scale

Time Frame

1 day

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

David Price, Prof

Organizational Affiliation

Research in Real Life

Official's Role

Study Director

Facility Information:

Facility Name

Research in Real Life Ltd

City

Oakington

State/Province

Cambridgeshire

ZIP/Postal Code

CB24 3BA

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

Undecided

IPD Sharing Plan Description

Principal investigator has not made a decision regarding a plan to share data at this point in time.

Citations:

PubMed Identifier

29108938

Citation

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.

Results Reference

derived

Learn more about this trial

The Evaluation of FeNO for Predicting Response to ICS in Subjects With Non-specific Respiratory Symptoms

We'll reach out to this number within 24 hrs