Clinical trial NCT06580600: PREcision Medicine Directed Corticosteroids In Children With preSchool Wheeze
Official title: A Single Centre Randomised, Feasibility Study Using Point-of-care (POC) Testing for Respiratory Viruses to Direct Oral Corticosteroids Use in Preschool-aged Children With Acute Wheeze.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Wheezing
Keywords: pre-school
wheeze
corticosteroid
point-of-care
Lead sponsor: Queen's University, Belfast
Sponsor class: OTHER
Collaborators: name: Asthma UK
name: Pediatric Emergency Research in the UK and Ireland (PERUKI)
First posted: 2024-08-30
Enrollment: 120
Sex: ALL
Minimum age (years): 24
Maximum age (years): 60
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: randomised (1:1) to receive OCS or No OCS (both of which are standard of care)
Primary purpose: OTHER

Brief summary: Young children frequently attend the emergency department (ED) with wheeze which is usually triggered by a virus infection, such as the common cold. Wheeze can be treated with inhaled medications and sometimes oral steroid medicines are also given to reduce swelling within the lungs. Unfortunately, oral steroids can have side effects. Despite lots of research there is no clear evidence that oral steroids work in young children with a wheeze attack. It is likely that some children get better quicker with oral steroids but deciding who to treat is difficult. This results in differences in care with some children receiving unnecessary oral steroids and others not receiving them when they could benefit.

The investigators hypothesise that in a subgroup of children with mild-to-moderate acute wheeze attacks, the viral trigger can predict their response to steroid medications. Previously, respiratory virus testing was too slow to be used to inform treatments in the ED. Now, point-of-care (POC) viral tests can provide results within 30 minutes. There is a research gap regarding the role of these tests in determining steroid responsiveness and outcomes in children presenting with acute wheeze in the pre-school population.

In order to address the hypothesis in a future definitive trial, the feasibility of using (POC) viral tests to randomise steroid treatments for children in a clinical study in the ED setting must be ascertained. The PRECISE Study will therefore be a single centre randomised, feasibility study enrolling approximately 60 pre-school aged children to inform a future definitive multi-centre Randomised Controlled Trial.

Detailed description: PRECISE will be a feasibility study; conducted as a single-centre, prospective, randomised open-label study. Participants will be screened by the clinical team from attendances to the local Emergency Department (ED). Participants meeting the study inclusion criteria, by age and symptoms, will be entered into a screening log. If the participant is not recruited the reason will be recorded. Participants will be assessed using the inclusion and exclusion criteria (described in other sections). Eligibility will be flagged by a member of the clinical team and then subsequently confirmed by a member of the research team. However, the medical care given to, and medical decisions made on behalf of, participants will be the responsibility of an appropriately qualified treating physician.

The research team member will discuss each eligible participant with their treating physician, to confirm agreement with study enrolment. Parents of eligible children will then be introduced to the research team to provide study information, confirm eligibility, and obtain informed consent. Families will be given time to read the Participant Information Sheets (PIS) and reflect on their discussion with the researcher who will then offer the opportunity to answer further questions. With written informed consent obtained, the participant will be enrolled. This will require the first nasal/nasopharyngeal swab (NPS) to be collected and tested for RSV and other respiratory viral infections. This NPS is for the purposes of the study but results will be made available to the treating clinician and the family. Based on the result of Participants' NPS they will then be randomised to receive oral corticosteroids (OCS) or no OCS through an automated process with a 1:1 ratio. Throughout this process clinicians will continue to perform investigations and administer additional standard of care treatment according to local hospital guidance. Administration of emergency standard of care treatment will not be delayed pending consent discussions or NPS result.

OCS therapy, if given, will be administered as oral dexamethasone according to local standard of care. If the participant vomits within 30 minutes of dexamethasone administration, it may be re-administered at the discretion of the treating clinician. As there is no blinding to the study participants or clinicians regarding the randomisation allocation, the treating clinician may choose to determine the OCS therapy plan at any point after enrolment, irrespective of study randomisation, based on the patient's clinical status.

After the initial ED presentation there are two other time points in the study, i) a review in 2 working days and a phone call at 28 days, post enrolment. UK BTS/SIGN guidance recommends all patients presenting with acute asthma or wheeze should be reviewed following discharge from ED/hospital within two working days. This is not routinely offered locally however, for the purposes of the study, participants will be offered a review with a clinical member of the research team and a repeat nasal swab event will take place. A member of the research team will call parents on day 28 to complete each child's research record.

Additionally, participants may consent to an optional finger prick blood testing at enrolment to elicit their blood eosinophil count using a Point of care (POC) white cell differential device. As with the NPS result, the family and clinicians will be made aware of the result.

Finally parents of participants in the PRECISE study will be invited to take part in semi-structured interviews after the day 28 call for further feasability and acceptability analysis.

Eligibility criteria: Inclusion Criteria:

* 24-60 months (infants from 24 months +0 days to 60 months + 0 days inclusive)
* Clinical diagnosis of acute wheeze
* Clinical uncertainty regarding the benefit of OCS as part of patient's standard care

Exclusion Criteria:

* Signs and symptoms of severe or life-threatening wheeze
* Patients presenting with wheeze suspicious for a non - respiratory cause
* Clinical evidence of shock or bacterial sepsis
* Past history of severe or life-threatening asthma or history of previous PICU admission with acute wheeze
* History of preterm birth (before 36+0 weeks gestation)
* Known immunodeficiency/ongoing immunosuppressive therapy
* Contraindication to oral corticosteroids
* Previously enrolled in the PRECISE Study

Primary outcomes:
measure: Recruitment
timeFrame: Screening Log completed through study completion, (estimated < 1 year)
measure: Adherance
timeFrame: measured at visit 2 and at 28 days post enrolment per patient. Throughout study completion, (estimated < 1 year)
measure: Timeliness
timeFrame: Timeliness measured on CRFs throughout study completion, (estimated < 1 year)
measure: Acceptability
timeFrame: Collected at 2 and 28 days post enrolment per patient. Data collected through study completion, (estimated < 1 year))
Secondary outcomes:
measure: viral aetiology
timeFrame: Through study completion, (estimated < 1 year)
measure: Concordance of test results
timeFrame: Between enrolment and the second visit. (Throughout study completion, (estimated < 1 year))
measure: Acceptability of tests to formulate plan
timeFrame: Data collected within one month of enrolment. Throughout study completion, (estimated < 1 year)
measure: Acceptability of tests to be repeated in study
timeFrame: Data collected within one month of enrolment. Throughout study completion, (estimated < 1 year)
measure: Airway immune response
timeFrame: Analysis to be performed within 1 year of study closure.
measure: blood eosinophil testing in acute setting
timeFrame: measured at enrolment and visit 2 per patient. Analysis to be completed within 6 months of study closure.
Other outcomes:
Locations:
city: Belfast
country: United Kingdom
facility: Royal Belfast Hospital for Sick Children
state: NI
Study officials:
affiliation: Queen's University, Belfast
name: Helen E Groves, PhD
role: PRINCIPAL_INVESTIGATOR
References: