A System to Classify Treatable Traits in Primary Care (SMART)

April 26, 2022 updated by: Richard Costello, Royal College of Surgeons, Ireland

This study proposes an approach to address an urgent unmet need in clinical practice, namely a pragmatic method of establishing what is the cause of a patient's complaint and the next steps to address this problem. In this study, the investigators will compare the proposed classification with current best practice of self-report, spirometry and FeNO. The investigators will compare the two approaches with a gold standard of deep characterisation by 3 separate diagnostic tests.

The investigators hypothesize that patients with symptoms of respiratory disease fall into one of four working groups based on accurate knowledge of three parameters, airflow, treatment use and the patient's symptoms.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

In respiratory diseases, the presenting symptoms are often a combination of cough, dyspnoea and wheeze. These three symptoms can be present in a significant number of conditions, including airways disease, cardiac disease and lung parenchymal disease. Making an accurate and timely clinical diagnosis is a challenge. Furthermore, physical deconditioning and co-morbidities such as obesity often create further obstacles to diagnosis. Even in the context of a clinical diagnosis of airways disease, differentiating between asthma and COPD is often not a straightforward decision. It takes time to establish by evaluating a patient's symptoms and major risk factors like smoking or allergy suggesting a particular aetiology. The diagnosis is further refined by spirometry or measures of FeNO when available and, importantly, the patient's response to treatment (1).

There are several practical problems that make this approach less than accurate. Symptoms do not correlate with airflow limitation because co-exiting conditions like obesity and deconditioning and complicating factors such as anxiety and poor recall make symptom-based diagnosis imperfect (2). Diagnostic testing with spirometry is impractical and only provides a snapshot of lung function. This test relies on disease activity being present at the time of testing appointment. This feature is uncommon given the intermittent nature of symptoms in asthma. It is not uncommon for clinicians trying to interpret a set of lung function to hear a patient say something like "I am fine now, but I was awful two weeks ago". This means that people are often incorrectly labelled as having or not having asthma. A landmark study showed that incorrect labelling of people as having asthma but this could not be proven objectively in over 30% of patients assessed in a national study in Canada (3). The measurement of airway inflammation with FeNO is inaccurate unless treatment use is measured concurrently (4). Because of these practical problems with testing, clinicians often have to rely on symptoms to make the diagnosis of asthma.

Furthermore, in the context of an accurately established obstructive airway disease, practical issues persist. For example, differentiating between asthma and COPD, decision on referral to a secondary centre, tailoring treatment and determining if disease is controlled. Tailoring inhaled therapy to the individual patient is a further complex decision in this patient cohort. However, poor adherence to ICS/LABA treatment is common, on average it is less than 50% among patients in primary care (5-7). Therefore, the diagnosis of airways disease in primary care is inherently inaccurate. This inaccuracy means that decisions on treatment effectiveness are also inaccurate. These common but important limitations lead to overuse of corticosteroids, antibiotics and beta-agonists with poor symptom control potential medication related morbidity. It follows that diagnostic accuracy and appropriate inhaled treatment use in airways disease has real and significant implications for patient safety, adverse outcomes, cost and waste.

To address these problems the INCA team have developed algorithms to classify and align lung function, treatment use and symptoms. This data is delivered via a novel CE marked platform to non-specialists with specific "suggestion scripts" (8). The classification divides patients into 4 main groups based on whether the airway function is or is not controlled if the patient took their treatment and if they remain symptomatic (9, 10). These groups are;

  1. The treatment intensify group: these people have persistent airflow obstruction/wide diurnal variation with good adherence. This trait requires additional bronchodilator and/or anti-inflammatory therapy and further tests.
  2. The obstructed, but poorly adherent group: These people have persistent airflow obstruction and poor adherence to treatment or poor inhaler technique. Adherence is assessed based on a novel metric time above threshold. Management/treatment is therefore focused on promoting-adherence and correct inhaler technique.
  3. The co-existing other condition group: This group have respiratory symptoms but no evidence of airflow obstruction. For these people airways disease is not the predominant problem and so should be evaluated with further tests and/or treatment of co-existing conditions.
  4. Controlled airflow and controlled symptoms group: this group need to continue their current inhaled treatment.

This classification accounts for the common issues of poor adherence and inaccurate diagnosis in asthma, which are reported to occur as commonly as 50% and 30% respectively. The classification also accounts for some more nuanced issues that would arise if a clinician were to rely simply on assessing adherence or lung function. These include confirming that people with uncontrolled asthma have been adherent and on the other hand, even if poorly adherent, that controlled patients do not need advice on extra adherence. This classification may help a clinician to deliver a personalised, accurate and efficient consultation to people with asthma in primary care.

In this proposal the investigators will test the feasibility of this approach among patients attending community general practitioners, those newly referred for assessment in secondary care and those advanced nurse practitioner respiratory clinics with a physician's clinical diagnosis of asthma, more specifically those who have chronic respiratory symptoms who their treating physician believe to be due to asthma, but who have not yet undergone laboratory lung function testing to establish the correct diagnosis of asthma.

Hypothesis

The investigators hypothesize that the simultaneous measurement and alignment of inhaler use and airflow can be used to organise patients with clinical diagnoses of asthma into one of four groups described above. This classification can subsequently be used as the basis for adjustments to treatment and further diagnostic testing as needed. The investigators will assess the value of this approach in primary care by comparing it with the standard approach of using point in time measures with FeNO and spirometry coupled with self-report.

Study Type

Observational

Enrollment (Anticipated)

200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Ireland
      • Dublin, Ireland
        • Beaumont Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Richard Costello
        • Sub-Investigator:
          • Patrick Kerr
        • Sub-Investigator:
          • Vincent Brennan

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients attending primary care, non-specialist respiratory clinics and advanced nurse practitioner clinics with undiagnosed persisting respiratory symptoms that have been attributed to asthma by a physician.

Description

Inclusion Criteria:

  1. Capable of understanding and willing to give voluntary informed consent prior to any protocol specific procedures being performed.
  2. Patients aged over 18 years.
  3. Present with persisting respiratory symptoms that are suggestive of airways disease.
  4. Capable of understanding and complying with the requirements of the protocol, including ability to attend for all 3 required visits.
  5. Able and willing to take inhaled medication via an Ellipta. [In the opinion of the investigator suitable for use of this inhaler.]
  6. Willing to use an electronic spirometer & peak flow meter.
  7. Currently prescribed Inhaled Corticosteroids (ICS) either alone or in combination with long acting beta agonists (ICS/LABA)

Exclusion Criteria:

  1. Have an active laboratory confirmed diagnosis of Asthma or COPD (with change to treatment within the last 8 weeks).
  2. Known previous sensitivity to ICS and Beta Agonist.
  3. Known significant (in the opinion of the investigator) concurrent medical disease that might mean that the patient cannot complete the full study.
  4. Intercurrent respiratory tract infection requiring antibiotic treatment in the last week
  5. Acute exacerbation of symptoms in the last 14 days requiring oral corticosteroid treatment
  6. Currently on specific concurrent potent cytochrome P450 3A4 (CYP3A4) medications; ketoconazole and ritonavir.
  7. Pregnancy
  8. Have greater than a 20-Pack Year Smoking History

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Respiratory
Patients attending primary care, non-specialist respiratory clinics and advanced nurse practitioner clinics with undiagnosed persisting respiratory symptoms that have been attributed to asthma by a physician.
Diagnostic test: Diagnostic testing
Data will be uploaded to a server where algorithms will be deployed that incorporate features related to treatment use and variables of airflow will allocate the care pathway into one of the 4 pathways. Treatment will be directed by this using a validated automated decision support system

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Comparing gold standard asthma diagnostics to PEFR (L/min)
Time Frame: 12 weeks
To assess the sensitivity of using serially measured, digital lung function measures (PEFR L/min) in confirming a diagnosis of asthma.
12 weeks
Comparing gold standard asthma diagnostics to repeated measures of lung function FEV1/FVC
Time Frame: 12 weeks
To assess the sensitivity of using serially measured, lung function FEV1/FVC in confirming a diagnosis of asthma.
12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Diurnal variation
Time Frame: 12 weeks
Assess the degree of diurnal variation in patients with mild asthma accounting for treatment effect with bronchodilator.
12 weeks
Activity levels
Time Frame: 12 weeks
Measure patients daily activity level (in steps per day)
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Royal College of Surgeons, Ireland

Collaborators

GlaxoSmithKline

Investigators

  • Principal Investigator: Richard Costello, Professor, Royal College of Surgeons, Ireland

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

May 16, 2022

Primary Completion (Anticipated)

May 16, 2024

Study Completion (Anticipated)

December 31, 2024

Study Registration Dates

First Submitted

April 12, 2022

First Submitted That Met QC Criteria

April 26, 2022

First Posted (Actual)

May 2, 2022

Study Record Updates

Last Update Posted (Actual)

May 2, 2022

Last Update Submitted That Met QC Criteria

April 26, 2022

Last Verified

April 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RC2021/01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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