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Severe Persistent AsthmaNCT02717689

A Pragmatic Trial of Corticosteroid Optimisation in Severe Asthma

A study testing Biomarker based adjustment of corticosteroid dose in people with Severe Persistent Asthma, run by Belfast Health and Social Care Trust at 11 sites in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study explores if a composite biomarker strategy predicts exacerbation risk in patients with asthma on high dose inhaled corticosteroid (+/-long-acting beta agonist) treatment and to evaluate the utility of this composite score to facilitate personalised biomarker specific titration of corticosteroid therapy in… Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Severe Persistent Asthma
What is being tested?
Biomarker based adjustment of corticosteroid dose
Could I receive a placebo?
No, everyone receives an active treatment
How many people
300 participants
Where
11 sitesUnited Kingdom
Study dates
1 Jan 2016to 19 Jun 2019
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 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age ≥ 18 and ≤ 80 years at screening visit
  • Able and willing to provide written informed consent and to comply with the study protocol
  • Baseline FeNO< 45 ppb at screening
  • Severe asthma confirmed after assessment by an asthma specialist. Diagnosed with asthma at least 12 months prior to screening
  • Current asthma treatment with LABA plus high doses of inhaled corticosteroids (≥1000 µg FP daily or equivalent)
  • Patients on an ICS/LABA single inhaler strategy must be switched to fixed dosing ICS/LABA for 4 weeks prior to screening
Show all 9Show fewer
  • Documented history of reversibility of ≥12% change in FEV1 within the past 24 months or during screening period, as demonstrated by:
  • Documented airflow obstruction (forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC ) <70%), where FEV1 has varied by ≥12% either spontaneously or in response to oral corticosteroid (OCS) therapy or bronchodilators either between or during clinic visits Or
  • A 20% drop in FEV1 (PC20) to methacholine <8 mg/mL or a 15% fall in FEV1 (PD15) after inhaling a cumulative dose of mannitol of ≤635 mg indicating the presence of airway hyperresponsiveness. If sites customarily use histamine to perform tests of airway responsiveness, this may be used in place of methacholine.

Who cannot join

  • Acute exacerbation requiring oral corticosteroids in previous 4 weeks before screening.
  • Known severe or clinically significant immunodeficiency, including, but not limited to, human immunodeficiency virus (HIV) infection.
  • Currently receiving or have historically received intravenous immunoglobulin for treatment for immunodeficiency.
  • If recently commenced on a leukotriene receptor antagonist or theophylline, stable on treatment for 4 weeks prior to screening
  • Known current malignancy or current evaluation for a potential malignancy or history of malignancy within 5 years prior to baseline. With the exception of basal-cell and squamous-cell carcinomas of the skin and carcinoma in situ of the cervix uteri that have been excised and cured.
  • Other clinically significant medical disease or uncontrolled concomitant disease despite treatment that is likely, in the opinion of the investigator, to require a change in therapy or impact the ability to participate in the study
Show all 19Show fewer
  • History of current alcohol, drug, or chemical abuse or past abuse that would impair or risk the subject's full participation in the study, in the opinion of the investigator
  • Current self-reported history of smoking (including electronic inhaled nicotine products) or former smoker with a smoking history of >15 pack-years
  • A current smoker is defined as someone who has smoked one or more cigarettes per day (or marijuana or pipe or cigar) for ≥ 30 days within the 24 months prior to the screening visit (Day -14) and / or cotinine positive at screening
  • Any individual who smokes (cigarettes, marijuana, pipe, or cigar) occasionally, even if for < 30 days within the 24 months prior to the screening visit (Day -14), must agree to abstain from all smoking from the time of consent through completion of study
  • A former smoker is defined as someone who has smoked one or more cigarettes per day (or marijuana or pipe or cigar) for ≥ 30 days in his or her lifetime (as long as the 30-day total did not include the 24 months prior to the screening visit [Day -14]).
  • A pack-year is defined as the average number of packs per day times the number of years of smoking.
  • Current use of an immunomodulatory/immunosuppressive therapy or past use within 3 months or five drug half-lives (whichever is longer) prior to the screening visit
  • Use of a biologic therapy including Omalizumab at any time during the 6 months prior to the screening visit.
  • Bronchial thermoplasty within prior 6 months of the screening visit
  • Initiation of or change in allergen immunotherapy within 3 months prior to the screening visit.
  • Treatment with an investigational agent within 30 days of the screening visit (or five half lives of the investigational agent, whichever is longer).
  • Female patients who are pregnant or lactating.
  • -

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

United Kingdom11 sites
  • Belfast Health and Social Care Trust

    Belfast, Northern Ireland, BT9 7AB

  • Heart of England NHS Foundation Trust

    Birmingham

  • NHS Greater Glasgow and Clyde

    Glasgow

  • University Hospitals of Leicester NHS Trust

    Leicester

  • Royal Brompton & Harefield NHS Foundation Hospital

    London

  • University College London Hospitals NHS Foundation

    London

  • University Hospitals of South Manchester NHS Trust

    Manchester

  • Newcastle upon Tyne Hospitals NHS Foundation Trust

    Newcastle upon Tyne

  • Nottingham University Hospitals NHS Foundation Trust

    Nottingham

  • Oxford University Hospitals NHS Trust

    Oxford

  • University Hospital of Southampton NHS Foundation Trust

    Southampton

Other trials in United Kingdom

About this study

Official title: A Randomised Pragmatic Trial Of Corticosteroid Optimisation In Severe Asthma Using A Composite Biomarker Algorithm To Adjust Corticosteroid Dose Versus Standard Care

This study explores if a composite biomarker strategy predicts exacerbation risk in patients with asthma on high dose inhaled corticosteroid (+/-long-acting beta agonist) treatment and to evaluate the utility of this composite score to facilitate personalised biomarker specific titration of corticosteroid therapy in this population.

Read the detailed description

Asthma affects an estimated 300 million people worldwide with a population prevalence of ca 15% in the UK. The WHO has estimated UK disability adjusted life-years per 100,000 population for asthma to be greater than diabetes and breast cancer. Much of this excessive disability is in the 10-20% of patients with asthma which is difficult to control despite currently available therapies. This high morbidity and disproportionate use of health care resources reflects the considerable unmet need in this patient group, and their significance for health care providers.

Asthma has been traditionally 'stratified' on the basis of response to 'step-wise' incremental treatment with inhaled corticosteroid (ICS) therapy forming the cornerstone of this approach. However, more recently, asthma has been stratified on the basis of inflammatory phenotype to better understand disease heterogeneity with a view to developing biomarkers of therapeutic response and for the better targeting of both new and existing treatments.

Investigators have recently examined the predictive value of a composite biomarker strategy using FeNO, blood eosinophils and serum periostin together to predict exacerbation risk in the placebo arms of clinical trials. Investigators propose to examine if this composite biomarker strategy predicts exacerbation risk in patients with asthma on high dose ICS (+/-long-acting beta agonist) treatment and to evaluate the utility of this composite score to facilitate personalised biomarker specific titration of corticosteroid therapy in this population. This study will examine subjects with FeNO<45 ppb and the scoring system will potentially allow identification of a 'low-risk' group who can safely reduce corticosteroid dose. This study will address a second important question of estimating the proportion of patients with severe disease who develop typical (T2)-driven eosinophilic inflammation on progressive corticosteroid withdrawal.

Being tested
Biomarker based adjustment of corticosteroid dose

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Biomarker based adjustment of corticosteroid doseOther

    The subject's corticosteroid dose will be adjusted based upon biomarker results (FeNO, eosinophils and periostin)

Study groups in NCT02717689
Study groupRoleWhat they receive
Biomarker armExperimentalBiomarker based adjustment of corticosteroid dose.
Receives: Other: Biomarker based adjustment of corticosteroid dose
Standard careNo interventionThe subject's corticosteroid dose will be adjusted based upon asthma symptom control and lung function

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Proportion of patients with any reduction in corticosteroid dose

    Proportion of patients with any reduction in oral or inhaled corticosteroid dose at any point over the 48 weeks of the study

    Measured: 48 weeks

Secondary outcomes (13)
  1. Rate of protocol-defined severe exacerbations per patient per year

    Measured: 48 weeks

  2. Time to first severe exacerbation from randomisation

    Measured: 48 weeks

  3. Dose of inhaled steroid at end of study

    Measured: Week 48

  4. Cumulative dose of inhaled corticosteroid during study

    Measured: 48 weeks

  5. Proportion of patients on oral corticosteroids at the end of the study

    Measured: Week 48

  6. Proportion of patients who decline to progress to oral corticosteroids despite composite biomarker score of 2

    Measured: 48 weeks

  7. Frequency of hospital admission for asthma

    Measured: 48 weeks

  8. Change in Asthma Control Questionnaire (ACQ-7)

    Measured: Week 48

  9. Change in FEV1 (volume)

    Measured: Week 48

  10. Change in exhaled breath nitric oxide level

    Measured: Week 48

  11. Change in blood eosinophil count

    Measured: Week 48

  12. Change in serum periostin levels

    Measured: Week 48

  13. Change in Asthma Quality of Life Questionnaire (AQLQ)

    Measured: Week 48

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Mar 2016 (estimated)
  2. Study start1 Jan 2016
  3. Primary completion19 Jun 2019
  4. Study completion19 Jun 2019

Resources

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
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Participant
Enrolment
300 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02717689
Sponsor's protocol ID
001
Status last verified
Jun 2020
First submitted
16 Mar 2016
Last updated
25 Jun 2020
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • McDowell PJ, Busby J, Hanratty CE, Djukanovic R, Woodcock A, Walker S, Hardman TC, Arron JR, Choy DF, Bradding P, Brightling CE, Chaudhuri R, Cowan D, Mansur AH, Fowler SJ, Diver SE, Howarth P, Lordan J, Menzies-Gow A, Harrison T, Robinson DS, Holweg CTJ, Matthews JG, Pavord ID, Heaney LG. Exacerbation Profile and Risk Factors in a Type-2-Low Enriched Severe Asthma Cohort: A Clinical Trial to Assess Asthma Exacerbation Phenotypes. Am J Respir Crit Care Med. 2022 Sep 1;206(5):545-553. doi: 10.1164/rccm.202201-0129OC.

    PubMed 35549845
  • Busby J, Matthews JG, Chaudhuri R, Pavord ID, Hardman TC, Arron JR, Bradding P, Brightling CE, Choy DF, Cowan DC, Djukanovic R, Hanratty CE, Harrison TW, Holweg CT, Howarth PH, Fowler SJ, Lordan JL, Mansur AH, Menzies-Gow A, Niven RM, Robinson DS, Walker SM, Woodcock A, Heaney LG; investigators for the MRC Refractory Asthma Stratification Programme. Factors affecting adherence with treatment advice in a clinical trial of patients with severe asthma. Eur Respir J. 2021 Sep 24;59(4):2100768. doi: 10.1183/13993003.00768-2021. Print 2022 Apr.

    PubMed 34561291
  • Heaney LG, Busby J, Hanratty CE, Djukanovic R, Woodcock A, Walker SM, Hardman TC, Arron JR, Choy DF, Bradding P, Brightling CE, Chaudhuri R, Cowan DC, Mansur AH, Fowler SJ, Niven RM, Howarth PH, Lordan JL, Menzies-Gow A, Harrison TW, Robinson DS, Holweg CTJ, Matthews JG, Pavord ID; investigators for the MRC Refractory Asthma Stratification Programme. Composite type-2 biomarker strategy versus a symptom-risk-based algorithm to adjust corticosteroid dose in patients with severe asthma: a multicentre, single-blind, parallel group, randomised controlled trial. Lancet Respir Med. 2021 Jan;9(1):57-68. doi: 10.1016/S2213-2600(20)30397-0. Epub 2020 Sep 8.

    PubMed 32916135
  • Hanratty CE, Matthews JG, Arron JR, Choy DF, Pavord ID, Bradding P, Brightling CE, Chaudhuri R, Cowan DC, Djukanovic R, Gallagher N, Fowler SJ, Hardman TC, Harrison T, Holweg CT, Howarth PH, Lordan J, Mansur AH, Menzies-Gow A, Mosesova S, Niven RM, Robinson DS, Shaw DE, Walker S, Woodcock A, Heaney LG; RASP-UK (Refractory Asthma Stratification Programme) Consortium. A randomised pragmatic trial of corticosteroid optimization in severe asthma using a composite biomarker algorithm to adjust corticosteroid dose versus standard care: study protocol for a randomised trial. Trials. 2018 Jan 4;19(1):5. doi: 10.1186/s13063-017-2384-7.

    PubMed 29301585

Questions about this trial

What is this clinical trial studying?

A study testing Biomarker based adjustment of corticosteroid dose in people with Severe Persistent Asthma, run by Belfast Health and Social Care Trust at 11 sites 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 9 inclusion and 19 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 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites 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?

Proportion of patients with any reduction in corticosteroid dose (time frame: 48 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 NCT02717689, which also lists 4 linked publications.

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 Jun 2020.

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