PRISTINE - Personalised Approach to Improve aSThma prescrIbing iN childrEn

NCT03269318 | Terminated Phase 4

• 1 other identifier: 183898
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

Asthma is one of the most common chronic diseases affecting children in the UK. Poorly controlled asthma manifests with chronic cough, wheeze and shortness of breath which in-turn has a significant negative impact on a child's quality of life, interfering with sleep, impairing exercise ability and resulting in frequent school absences and hospital admissions. Management of paediatric asthma in the UK is directed by the British Thoracic Society (BTS) Guidelines, which recommend a stepwise (one to five) treatment plan. Step three of the management guideline for children aged 5-12 years of age recommends the addition of the preventer inhaled medication, including long-acting β2 agonists such as salmeterol. However, there is a wide variation in response to this medication with approximately one in seven people, with a specific genetic change, found to have an increase in asthma symptoms in association with the use of thisiss medication. A related medicine, formoterol, is used less commonly in children with asthma. In this study, the investigators will aim to identify children with asthma whose symptoms are poorly controlled on inhaled long-acting beta2 agonists. Via a simple saliva test, the investigators will identify the presence or absence of the specific genetic change potentally influencing the effectiveness of treatment with salmeterol or related longacting beta2 agonists thus enabling the investigators to recommend either salmeterol or an alternative medication for the treatment plan such as montelukast. The investigators will randomise the patients into two groups; to receive "personalised care" where the choice of controller medication would be based on the child's gene test results and predicted response to long-acting beta2 agonists, or "standard care" following the BTS guidelines at the clinician's discretion without knowledge of the gene test results. The investigators aim to measure whether this individualized approach to asthma prescribing results in improved control of asthma symptoms and overall quality of life. Targeting treatment to a child's specific genetic make-up is a concept known as "personalised medicine".

Conditions

Asthma

Outcome Measures

Primary Outcomes (4)

• Are children with asthma and their parents willing to be recruited and randomised to a trial of genotyping and personalised management for asthma? Qualitative interview

  Recruitment rates will be measured as rate of invited participants who are eligible and consenting and will be reported in a Consolidated Standards of Reporting Trials (CONSORT) participant flowchart.

  Baseline to 3 months

• Are there retention issues? If yes, at what stages did these occur? What were the reasons? Qualitative interview

  Acceptability of allocation procedures will be assessed by examining reasons for dropout in discontinuing participants and comparing attrition rates between the two study groups and between participants who did and did not receive their preferred allocation. Attrition rates will be established as discontinuation of intervention and loss to follow-up measurement for both groups

  Baseline to 3 months

• Are follow-up data complete?

  Suitability of outcome measures will be evaluated based on completion rates and rates of missing data

  Baseline to 3 months

• Acceptability of personalised approach

  All participants and their parents/guardians will be invited to have a semi-structured interview with a member of the research team in order to discuss their experiences of living with and managing their asthma. To enhance communication and ensure the child's perspective is captured, children will be invited to make a drawing of what it is like to have asthma and what it feels like when they take their asthma medication. The research team interviewing will then discuss the drawings (as a visual cue) in simple language with each child to understand what the child means.

  Baseline to 3 months

Secondary Outcomes (7)

• Childhood Asthma Control Test

  Baseline to 3 months

• Lung Function

  Baseline to 3 months

• Days unable to complete usual activities

  Baseline to 3 months

• Use of medication

  Baseline to 3 months

• Use of health services

  Baseline to 3 months

Study Arms (2)

Personalised Medicine

EXPERIMENTAL

Personalised Medicine who will be prescribed controller medication based on genetic test, Arg/Arg or Arg/Gly - montelukast (LTRA) or Gly/Gly -salmeterol (LABA).

Drug: Montelukast or Salmeterol or Theophylline or Steroid

Standard Care

NO INTERVENTION

Standard of care (Standard Care will be prescribed controller medication based on guidelines)

Interventions

Montelukast or Salmeterol or Theophylline or Steroid DRUG

Medication will be patient specific according to their current medication, clinical symptoms and genotype. It will be from a choice of; leukotriene receptor antagonist (montelukast), long-acting beta2 agonist (salmeterol), theophylline or increase dose of inhaled steroid.

Personalised Medicine

Eligibility Criteria

• Age: 5 Years - 11 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Parent/Guardian/Participant is willing and able to give informed consent/assent
• Physician-diagnosed asthma that is inadequately controlled as per view of doctor (for example, history of at least two emergency visits to GP or hospital over the previous year, frequent use of blue inhaler (three times or more per week))
• Aged 5-11 years (inclusive)
• Children who are already on at least 400 micrograms per day inhaled beclomethasone or equivalent and hence ready to be prescribed inhaled long-acting beta2 agonists and/or other add-on medication or are already on inhaled long-acting beta2 agonists and/or other add-on medication

You may not qualify if:

• Parent/Guardian/Participant is unwilling or unable to give informed consent/assent
• Known contraindication to montelukast or salmeterol
• Other known significant airway or lung disease (e.g. chronic lung disease of prematurity, cystic fibrosis or congenital airway abnormalities) or other co-existing serious disease such as congenital cardiac disease
• Poor inhaler technique and/or history of poor adherence on checking following standard procedure at the clinic
• Participating in another clinical trial (other than observational trials and registries) concurrently or within 30 days prior to screening for entry into this study

Sponsors & Collaborators

• Brighton and Sussex University Hospitals NHS Trust: lead

Study Sites (1)

BrightonNHS

Brighton, East Sussex, BN2 5BE, United Kingdom

Location

MeSH Terms

Conditions

Asthma

Interventions

montelukast; Salmeterol Xinafoate; Theophylline; Steroids

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Albuterol; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines; Xanthines; Alkaloids; Heterocyclic Compounds; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Somnath Prof Mukhopadhyay

  Brighton and Sussex University Hospital NHS Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be allocated to one of two groups as per block randomisation, with no stratification or minimisation to Group 1; Personalised Medicine who will be prescribed controller medication based on genetic test, Arg/Arg or Arg/Gly - montelukast (LTRA) or Gly/Gly -salmeterol (LABA). While Group 2, Standard Care will be prescribed controller medication based on guidelines.

Study Record Dates

• First Submitted: July 11, 2017
• First Posted: August 31, 2017
• Study Start: July 1, 2017
• Primary Completion: August 30, 2019
• Study Completion: August 30, 2019
• Last Updated: December 18, 2019

Record last verified: 2019-12

Locations

GB (1)