Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02517099 |
| Other study ID # |
165460 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
June 5, 2015 |
| Est. completion date |
August 17, 2018 |
Study information
| Verified date |
May 2022 |
| Source |
Imperial College London |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
This is a single-centre, randomised-controlled trial, comparing management of preschool
wheeze. It specifically aims to compare management of preschool wheeze using current clinical
guidelines to management determined by eosinophilic inflammation and infection. Participants
will be children aged 1-5 years who have recurrent wheezing and will be allocated to one of
two treatment groups, either current clinical care or pathological phenotype based
management. They will be asked to make 2 study visits to the Royal Brompton Hospital over the
course of 4 months.
Description:
This study will determine the efficacy of treating preschool wheeze based on objective
biomarkers of inflammation and presence of bacterial infection, and compare this to current
clinical guidelines based management. Subjects will be recruited from out-patient clinics and
attend for a screening/research visit during which assessments of pathological phenotype
(bacterial infection and inflammation) will be made from induced sputum and blood. Their
clinical phenotype will be determined by the Consultant. Subsequently, patients will be
randomised to one of two arms:
i) current clinical care ( as directed by their Consultant) ii) pathological phenotype based
management- presence of eosinophilia in blood (_> 2%) or induced sputum (>2.4%) - will
receive twice daily inhaled steroids ( beclometasone 200mcg bd) for 4 months, presence of
bacterial infection in induced sputum or oropharyngeal swab- will receive 4 weeks of
antibiotics targeted to the isolate, IF BOTH eosinophilic inflammation AND infection are
present, then inflammation alone will be treated for 4 months.
All patients will continue on as required bronchodilator therapy, and any other
anti-inflammatory therapy ( other than inhaled steroids) e.g. montelukast.
All participants will undergo an initial research/screening visit which will involve the
following tests:
Full blood count Total serum immunoglobulin E and radioallergosorbent test to house dust
mite, grass pollen, tree pollen, cat, dog, aspergillus, milk, egg, peanut Assessment of lung
function by incentive spirometry and lung clearance index (LCI) using the multiple breath
washout technique Exhaled nitric oxide- using the offline tidal breathing technique Sputum
induction using nebulised hypertonic saline Oro- pharyngeal swab Symptom questionnaire Health
related quality of life questionnaire
Management in the pathological phenotype arm:
1. Eosinophilic inflammation, no bacterial infection:
Children with sputum eosinophils >2.4% or blood eosinophils equal to and above 2% will
be defined as eosinophilic and management will be as follows:
i) Regular inhaled steroids ( beclometasone 200mcg bd) for 4 months in those previously
not on any regular therapy.
ii) Of children who have already been prescribed inhaled steroid therapy, those with an
eosinophilic phenotype will continue for a further 4 months.
iii) Children who have already been prescribed a regular leukotriene receptor antagonist
will continue this and regular inhaled steroids (beclometasone 200mcg bd) will be added
to their maintenance therapy for 4 months.
iv) Use of as required bronchodilator therapy will continue
2. Non- eosinophilic, no inflammation, no infection:
Children with either sputum eosinophils _<2.4% or blood eosinophils <2% will be defined
as non- eosinophilic and management will be as follows:
i) Use of as required bronchodilators for acute symptoms ii) Non- eosinophilic children
that have already been prescribed regular inhaled steroids will be asked to stop them
for 4 months Children with no bacterial growth from oropharyngeal swab or induced
sputum, and without eosinophilic inflammation will continue management according to the
non-eosinophilic, no inflammation, no infection profile.
3. Bacterial infection, no eosinophilic inflammation:
Children with a positive bacterial culture result from oropharyngeal swab or induced
sputum will be treated with a 4 week course of antibiotics. Four weeks of antibiotic
therapy will be used as this has been shown to be beneficial in a previous study of
severe preschool wheeze. If these children have already been prescribed regular inhaled
steroids, they will be stopped for 4 months.
4. Eosinophilic inflammation AND bacterial infection:
Children with raised eosinophils in induced sputum or blood AND positive bacterial culture
will be managed according to the eosinophilic inflammation alone guideline. They will only be
given inhaled steroids for 4 months, and no antibiotics. This is to assess only one
intervention at a time. However, the investigators do not anticipate many children will be in
this group as our previous data shows those with positive bacterial cultures are very
unlikely to have eosinophilia.
Management in the clinical guidelines arm:
The children will be treated as directed by their Consultant Paediatrician. The prescription
for the drugs to be used will be dispensed from the pharmacy department at the Royal Brompton
Hospital- as directed by the clinician. Usually only 2 weeks of medication is prescribed by
the pharmacy, but for this trial 4 months' supply will be given.
Concomitant treatment
The following medication will be allowed to continue during the intervention period in both
study arms:
1. Use of rescue medication with bronchodilators for acute symptoms- salbutamol and/or
ipratropium bromide
2. Use of leukotriene receptor antagonist- montelukast- can continue regardless of whether
it is being taken regularly or as required for acute symptoms
Monitoring:
The trial will be monitored according to the monitoring plan agreed and written by the
Sponsor, based on internal risk assessment procedure. Where appropriate the CI will be asked
to complete a copy of the Sponsor's self-monitoring template. It is the responsibility of the
CI to ensure this is completed and submitted to the research organisation on request. It is
the responsibility of the research organisation to determine the monitoring risk assessment
and explain the rationale.
The study may be subject to inspection and audit by Imperial College London under their remit
as Sponsor, the Study Coordination Centre and other regulatory bodies to ensure adherence to
good clinical practice.
Statistics and Data analysis:
Categorical data will be presented as number and percentage and comparisons between groups
done using the chi squared or Fishers exact test. All numerical data will be tested for
normality and normally distributed data will be presented as mean standard deviation and
comparisons between groups done using the 2 sample independent t test. For the data that are
not normally distributed the median (IQR) will be presented and comparisons between groups
done using the Mann-Whitney test. Poisson regression will be done to determine the factors
that affect the primary endpoint, the number of unplanned hospital visits.
There will be data checks to compare data entered into the registry, against predefined rules
for range using the INFORM database.
Type of subjects to be recruited:
All subjects will be aged between 1 and 5 years old. All subjects will have moderate to
severe preschool wheeze, defined as _>2 oral steroid bursts for acute wheeze in the last 12
months, with at least one oral steroid burst in the last 6 months.
Number of subjects:
Based on published data for children with moderate preschool wheeze it is apparent that
approximately five healthcare attendances occur per child per year. In the current study, the
investigators wish to reduce the proportion of healthcare contacts by at least one-third per
year. In order to achieve this with 80% power, and accepting statistical significance at the
5% level, the investigators require a minimum of 36 evaluable patients with moderate wheeze
per group. Evaluable patients are those from whom at least a blood sample to assess
inflammation and an oropharyngeal swab to determine infection can be obtained prior to
randomisation. A total of at least 72 children will therefore be recruited. However, this is
the minimum number, and the investigators aim to recruit 100 children (50 per group) if
possible.
The number of subjects is not based on a precise power calculation as this is a proof of
concept study to determine the feasibility of this approach, and to inform a future power
calculation for a large multi-centre trial addressing the same question.
