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Trial registered on ANZCTR


Registration number
ACTRN12618000781246
Ethics application status
Approved
Date submitted
9/02/2018
Date registered
9/05/2018
Date last updated
22/04/2020
Date data sharing statement initially provided
13/05/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Preterm Paediatric Inhaled Corticosteroid Intervention (PICSI)
Scientific title
Inhaled corticosteroids for treating active lung disease in survivors of preterm birth
Secondary ID [1] 294005 0
Nil
Universal Trial Number (UTN)
Trial acronym
PICSI
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic lung disease of prematurity 306518 0
Condition category
Condition code
Respiratory 305626 305626 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Fluticasone propionate
125 mcg twice daily for 12 weeks
Inhaled actuation. Parent-assisted, at-home administration.

Adherance will be recorded by participants and return of the product at the end of trial will allow for dose counting for each participant.
Intervention code [1] 300276 0
Treatment: Drugs
Comparator / control treatment
Placebo - propellant only inhaler.
Maufacturer: GlaxoSmithKline

The placebo and study treatment are both manufactured by GlaxoSmithKline to ensure true blinding. The placebo contains propellant only, and has no other active ingredients.
Control group
Placebo

Outcomes
Primary outcome [1] 304739 0
Mean change in levels of inflammatory markers from laboratory analysis of exhaled breath condensate collected at baseline (Visit 1) and after 12-week treatment endpoint (Visit 2).
Timepoint [1] 304739 0
Visit 2 (within 2 weeks of completing the 12-week intervention).
Secondary outcome [1] 342991 0
Fold changes in the pulmonary metabolomics profile from baseline to endpoint (Visit 2) as assessed by metabolomic analysis of exhaled breath condensate.
Timepoint [1] 342991 0
Visit 2 (within 2 weeks of completing the 12-week intervention).
Secondary outcome [2] 342992 0
Composite outcome.
Change in lung function from baseline to endpoint (Visit 2) as measured by:
- Spirometry (forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), ratio of FEV1 to FVC (FEV1/FVC) and forced flows as predicted values developed by the Global Lung Function Initiative)
- Respiratory mechanics (respiratory resistance, respiratory reactance, resonant frequency and the area under the reactance curve).
- Exhaled nitric oxide levels (FeNO)
Timepoint [2] 342992 0
Visit 2 (within 2 weeks of completing the 12-week intervention).
Secondary outcome [3] 342993 0
Composite outcome - change in bronchodilator responsiveness from baseline to endpoint (Visit 2) as measured by spirometry (forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), ratio of FEV1 to FVC (FEV1/FVC) and forced flows as predicted values developed by the Global Lung Function Initiative) and respiratory mechanics (respiratory resistance, respiratory reactance, resonant frequency and the area under the reactance curve) post-bronchodilator (400 micrograms salbutamol).
Timepoint [3] 342993 0
Visit 2 (within 2 weeks of completing the 12-week intervention).
Secondary outcome [4] 342994 0
Change in respiratory symptoms from baseline to endpoint (Visit 2) as assessed by respiratory symptoms questionnaire (study specific, based on validated general and respiratory questionnaires including those used by the West Australian Birth Cohort (Raine) study).
Timepoint [4] 342994 0
Visit 2 (within 2 weeks of completing the 12-week intervention).

Eligibility
Key inclusion criteria
Preterm-born participants: Children aged 6-12 years who were born at less than or equal to 32 weeks gestation,
Healthy volunteers: Children aged 6-12 years who were born >37 weeks gestation who have no recurrent respiratory symptoms.
Minimum age
6 Years
Maximum age
12 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
• Severe congenital abnormalities
• Severe cardiopulmonary defects
• Severe neurodevelopmental impairment
• Glucocorticoid use within the past 3 months

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation will be double-blinded, with central randomisation by computer and the holder of the allocation schedule (hospital pharmacy) being external to the trial.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Efficacy
Statistical methods / analysis
At the completion of data collection, there will be data from 250 participants (50 term controls; 100 very preterm without BPD; 100 very preterm with BPD) with 2 time points each. Interim analysis will take place halfway through the study.

The sample size has been determined with two aims under consideration: 1) observing a difference between cohorts in the quantity of inflammatory markers, and 2) observing a difference in inflammation post intervention with ICS. Assuming a loss of data of <20%, we will have: >90% power to detect both a two-fold increase in inflammatory markers (e.g. a difference of 3.9 pg/mL in 8-isoprostane concentrations) between cohorts based on a two-sided t-test with a strict alpha of 0.01. The sample size provides >85% power to detect a difference (at p<0.05) of >0.5 SD in any post-intervention measure (e.g. FEV1),
The sample size to be recruited is greater than that used in the only previously reported metabolomics study in BPD [29]. The success of this indicative study, coupled with our increased data collection from across the lung disease spectrum (based on the between group separation), suggests our study design will provide sufficient data for these analytic models to both converge and be informative. We will therefore recruit 200 participants born very preterm (100 with BPD) and 50 controls to account for a conservative 20% participant drop out, inability to perform tests or loss to follow-up.

The analysis of inflammation and lung function post-intervention will be assessed via an ANCOVA framework, utilising linear regression to adjust for baseline lung function. For the advanced, exploratory multivariate modelling (machine learning), the standard procedure for producing a robust screening model is to employ stratified k-fold cross-validation.

Recruitment
Recruitment status
Suspended
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 9996 0
Perth Children's Hospital - Nedlands
Recruitment postcode(s) [1] 18835 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 298631 0
Government body
Name [1] 298631 0
National Health and Medical Research Council
Address [1] 298631 0
Research Committee Secretariat NHMRC GPO Box 1421
Canberra ACT 2601
Country [1] 298631 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Telethon Kids Institute
Address
15 Hospital Avenue
Nedlands
Perth WA 6009
Country
Australia
Secondary sponsor category [1] 297800 0
None
Name [1] 297800 0
N/A
Address [1] 297800 0
N/A
Country [1] 297800 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299590 0
Child and Adolescent Health Service Human Research Ethics Committee
Ethics committee address [1] 299590 0
Perth Children's Hospital
15 Hospital Avenue
Nedlands Western Australia 6009
Ethics committee country [1] 299590 0
Australia
Date submitted for ethics approval [1] 299590 0
13/02/2018
Approval date [1] 299590 0
30/05/2018
Ethics approval number [1] 299590 0
RGS367

Summary
Brief summary
More than 15 million babies are born preterm each year. Life-long pulmonary consequences, including recurrent respiratory symptoms, airway obstruction, airway hyper-reactivity and declining lung function are especially evident in those born very preterm (<32 weeks gestation). Emerging evidence, such as the presence of sputum neutrophils and oxidative stress markers in adolescent survivors of very preterm birth, suggest that the respiratory sequelae may be the result of an active inflammatory driven disease process rather than the fixed, non-progressive disease often described. Further studies are urgently required to understand the persistence of pulmonary inflammation beyond the neonatal period and how it contributes to the respiratory morbidity experienced by this vulnerable population.
This project aims to characterise the pulmonary metabolome and quantify biomarkers in the exhaled breath of children born very preterm, aged 6-12 years, by comparing these samples to those from healthy, age-matched controls. Biomarker and metabolite levels will be related to neonatal and clinical data including respiratory symptoms and lung function outcomes, to identify children at increased risk of progressive lung disease. Further, we will assess the effect of treatment with inhaled corticosteroids on inflammatory mediators and the pulmonary metabolome in children born very prematurely.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 80946 0
Dr Shannon Simpson
Address 80946 0
Telethon Kids Institute
15 Hospital Avenue
Nedlands
Perth WA 6009
Country 80946 0
Australia
Phone 80946 0
+61 8 6319 1631
Fax 80946 0
Email 80946 0
Shannon.Simpson@telethonkids.org.au
Contact person for public queries
Name 80947 0
Dr Shannon Simpson
Address 80947 0
Telethon Kids Institute
15 Hospital Avenue
Nedlands
Perth WA 6009
Country 80947 0
Australia
Phone 80947 0
+61 8 6319 1631
Fax 80947 0
Email 80947 0
Shannon.Simpson@telethonkids.org.au
Contact person for scientific queries
Name 80948 0
Dr Shannon Simpson
Address 80948 0
Telethon Kids Institute
15 Hospital Avenue
Nedlands
Perth WA 6009
Country 80948 0
Australia
Phone 80948 0
+61 8 6319 1631
Fax 80948 0
Email 80948 0
Shannon.Simpson@telethonkids.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Individual Participant Data will not be shared to protect participant privacy. No consent is being sought for individual participant data sharing.
What supporting documents are/will be available?
No other documents available
Summary results
No Results