Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12618000781246
Ethics application status
Approved
Date submitted
9/02/2018
Date registered
9/05/2018
Date last updated
9/12/2022
Date data sharing statement initially provided
13/05/2019
Date results information initially provided
9/12/2022
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
Change in lung function from baseline to endpoint as measured by the spirometry outcome Forced Expiratory Volume in 1 second (FEV1).
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), 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).
Secondary outcome [5] 416686 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 [5] 416686 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
Sex
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
The primary efficacy outcome for the trial was an improvement in FEV1 following 12 weeks of fluticasone treatment. Efficacy was defined as a 0·5 z-score improvement in FEV1, the value previously determined as a clinically significant change in FEV1 . A minimum sample size of 126 participants (63 per group) was required to detect this 0·5 z-score difference with 80% power.
An intention-to-treat analysis was conducted to compare the change in primary lung function endpoints following treatment using a linear regression model with the difference following treatment as the outcome and treatment as the predictor. All hypothesis tests were two sided with p-values of <0·05 considered statistically significant.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
3/09/2018
Actual
23/10/2018
Date of last participant enrolment
Anticipated
30/06/2021
Actual
4/02/2022
Date of last data collection
Anticipated
1/09/2020
Actual
5/05/2022
Sample size
Target
250
Accrual to date
Final
214
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
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). However, there are no evidence-based interventions available or recommended to halt or reverse chronic lung disease in survivors of preterm birth after they leave the neonatal intensive care unit.
This project aims to assess the effect of a 12-week treatment with inhaled corticosteroids (fluticasone propionate) on the lung function of children born very prematurely and identify the clinical features of those with a positive response to inhaled corticosteroid therapy.
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
[email protected]
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
[email protected]
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
[email protected]

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 Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseInhaled corticosteroids to improve lung function in children (aged 6-12 years) who were born very preterm (PICSI): a randomised, double-blind, placebo-controlled trial.2023https://dx.doi.org/10.1016/S2352-4642%2823%2900128-1
N.B. These documents automatically identified may not have been verified by the study sponsor.