ANZCTR - Registration

Please note the ANZCTR will be unattended from Friday 20 December 2024 for the holidays. The Registry will re-open on Tuesday 7 January 2025. Submissions and updates will not be processed during that time.

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

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

ACTRN12624000851561

Ethics application status

Approved

Date submitted

27/04/2024

Date registered

9/07/2024

Date last updated

9/07/2024

Date data sharing statement initially provided

9/07/2024

Type of registration

Prospectively registered

Titles & IDs

Public title

BLUEPRINT: Predicting Long-term Outcomes of Prematurity from Early Life Events

Scientific title

Predicting Long-term Outcomes of Prematurity from Early Life Events

Secondary ID [1]

Nil Known

Universal Trial Number (UTN)

U1111-1268-5755

Trial acronym

The BLUEPRINT Study

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Prematurity

Respiratory Disease

Chronic Lung Disease of Infancy

Condition category

Condition code

Respiratory

Normal development and function of the respiratory system

Respiratory

Other respiratory disorders / diseases

Reproductive Health and Childbirth

Complications of newborn

Intervention/exposure

Study type

Observational

Patient registry

True

Target follow-up duration

Target follow-up type

Years

Description of intervention(s) / exposure

The BLUEPRINT Study is a prospective longitudinal observational cohort study using clinical, lung imaging and plasma protein data to define the early postnatal respiratory endotypes following preterm birth, and to determine the relationship with bronchopulmonary dysplasia (BPD) and 1- and 2-year respiratory outcomes.

The primary objective of the BLUEPRINT Study is to comprehensively define respiratory endotypes in the first 7 days after birth in preterm infants born between 22 and 32 weeks’ inclusive gestation. The secondary objectives include: 1) To develop the first functional classification of preterm respiratory disease using a combination of clinical, lung imaging and molecular biomarkers, 2) To delineate how specific early preterm phenotypes relate to a diagnosis of BPD and develop a predictive modelling tool for early diagnosis, and 3) To characterise the respiratory and general health of preterm infants in the first 2 years corrected age.

Infants born between 22+0 and 31+6 weeks’ gestation admitted to a participating centre from whom parental informed consent can be obtained will be considered eligible. Eligible and enrolled infants will have clinical data relating to their antenatal, maternal and postnatal respiratory and neonatal intensive care course collected at pre-defined time points between birth and neonatal intensive care unit (NICU) discharge. In addition, a maximum of 0.5 ml of blood will be collected at 72 hours and 7 days for analysis of lung-specific proteins in the plasma using proteomics, and a brief lung ultrasound (LUS) and electrical impedance tomography (EIT) image of the lung performed at 48 and 72 hours, 7, 14 and 28 days, and then at 36 weeks’ corrected gestational age (BPD diagnosis). LUS, EIT and plasma proteomic analysis are not considered standard of care in the NICU and will only be performed in infants participating in the BLUEPRINT study, however these measurements will not be altering clinical care or clinical course of the participating infant. Lung imaging and assessment of respiratory health using standardised parental questionnaires will be repeated at 1 and 2 years corrected age in preterm survivors.

The parental questionnaires include:
PARCA-R questionnaire of developmental status (approximately 30 min to complete)
General Infant Respiratory and Health questionnaire (approximately 10-15 min to complete)

550 infants will be studied from all Level 6 Neonatal Intensive Care Units in Victoria. Recruitment and follow up is anticipated to be finished in approximately 5 years.

Intervention code [1]

Early Detection / Screening

Intervention code [2]

Diagnosis / Prognosis

Comparator / control treatment

No control Group

Control group

Uncontrolled

Outcomes

Primary outcome [1]

The types of respiratory endotypes present in preterm infants born between 22+0 and 31+6 weeks’ gestation at 7 days after birth.

Functional respiratory endotypes are defined from clinical, plasma protein and lung imaging measures using latent class analysis followed by external validation via group-based trajectory modelling.

Timepoint [1]

At 7 days after birth

Secondary outcome [1]

Level of assisted respiratory support using observational data at 72 hours after birth in preterm infants born between 22+0 and 31+6 weeks’ gestation.

Timepoint [1]

72 hours after birth

Secondary outcome [2]

Functional models of the preterm respiratory disease phenotype using a combination of clinical markers collected from medical records, lung imaging collected from measures of aeration and ventilation using lung ultrasound and electrical impedance tomography and molecular biomarkers determined from blood samples.

Timepoint [2]

At 7 days after birth

Secondary outcome [3]

Diagnosis of bronchopulmonary dysplasia (defined Walsh Definition and Jensen Grade of Severity).

Timepoint [3]

36 weeks’ corrected post menstrual age.

Secondary outcome [4]

Duration of invasive mechanical ventilation during primary Neonatal Intensive Care Unit admission (from medical records).

Timepoint [4]

Discharge from primary Neonatal Intensive Care Unit Admission

Secondary outcome [5]

Duration of supplementary oxygen support during primary Neonatal Intensive Care Unit admission (from medical records).

Timepoint [5]

Discharge from primary Neonatal Intensive Care Unit Admission

Secondary outcome [6]

The need for supplementary oxygen at discharge home from primary Neonatal Intensive Care Unit admission (from medical records).

Timepoint [6]

Discharge from primary Neonatal Intensive Care Unit Admission

Secondary outcome [7]

Mortality during primary Neonatal Intensive Care Unit admission.

Timepoint [7]

Discharge from primary Neonatal Intensive Care Unit Admission

Secondary outcome [8]

Respiratory health of preterm infants in the first 2 years (corrected) after birth as defined by composite of Respiratory health status questionnaire, gravity-dependent and right-left lung centre of ventilation and homogeneity index (electrical impedance tomography) and lung ultrasound scores.

Timepoint [8]

2 years corrected age

Secondary outcome [9]

Overall childhood health of preterm infants in the first 2 years (corrected) after birth assessed from medical records and clinical assessment at 2 years of age.

Timepoint [9]

2 years corrected age

Secondary outcome [10]

Neurodevelopmental state of preterm infants in the first 2 years (corrected) after birth using the PARCA-R questionnaire

Timepoint [10]

2 years corrected age

Secondary outcome [11]

Early childhood respiratory health assessed from medical records and clinical assessment at 2 years corrected age.

Timepoint [11]

2 years corrected age

Secondary outcome [12]

Early childhood respiratory health assessed from medical records and clinical assessment at 1 years corrected age.

Timepoint [12]

1 year corrected age

Secondary outcome [13]

Lung ultrasound-derived measures of respiratory status using the standardised lung ultrasound score at 28 days after birth.

Timepoint [13]

28 days after birth

Secondary outcome [14]

Regional ventilation and aeration as measured using electrical impedance tomography at 14 days after birth.

Timepoint [14]

14 days after birth

Secondary outcome [15]

Regional ventilation and aeration as measured using electrical impedance tomography at 28 days after birth.

Timepoint [15]

28 days after birth

Secondary outcome [16]

Lung-specific plasma protein expression at 72 hours.

Timepoint [16]

72 hours after birth

Secondary outcome [17]

Lung-specific plasma protein expression at 7 days after birth.

Timepoint [17]

7 days after birth

Secondary outcome [18]

Regional ventilation and aeration as measured using electrical impedance tomography at 3 days after birth.

Timepoint [18]

3 days after birth

Secondary outcome [19]

Regional ventilation and aeration as measured using electrical impedance tomography at 7 days after birth.

Timepoint [19]

7 days after birth

Secondary outcome [20]

Lung ultrasound-derived measures of respiratory status using the standardised lung ultrasound score at 3 days after birth.

Timepoint [20]

3 days after birth

Secondary outcome [21]

Lung ultrasound-derived measures of respiratory status using the standardised lung ultrasound score at 14 days after birth.

Timepoint [21]

14 days after birth

Secondary outcome [22]

Supplementary oxygen levels using observational data at 72 hours after birth in preterm infants born between 22+0 and 31+6 weeks’ gestation.

Timepoint [22]

72 hours after birth

Secondary outcome [23]

Respiratory function using observational data at 72 hours after birth in preterm infants born between 22+0 and 31+6 weeks’ gestation.

Timepoint [23]

72 hours after birth

Eligibility

Key inclusion criteria

Each infant must meet all inclusion criteria to be eligible for enrolment in the BLUEPRINT study:
1. Born between 22+0 and 31+6 weeks’ gestation.
2. Birth admission in a participating perinatal Victorian Neonatal Intensive Care Unit.
3. The infant has a parent/legal representative capable of understanding the informed consent document and providing consent on the infant’s behalf AND consent is obtained antenatally or within 72 hours from birth.

Minimum age

0 Hours

Maximum age

72 Hours

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

If any of the following exclusion criteria are met, the infant will be ineligible for enrolment in the BLUEPRINT study:
1. Infants with a known major congenital anomaly (such as oesophageal atresia and central nervous system anomalies), congenital cardiac disease, congenital diaphragmatic hernia, congenital lung abnormalities and/or pulmonary hypoplasia.
2. Pulmonary hypoplasia due to anhydramnios or oligohydramnios before 22 weeks in which the neonatal clinician anticipates that pulmonary hypoplasia related respiratory failure will be the major respiratory problem in early postnatal life.
3. Primary cause of admission unrelated to prematurity.
4. Refusal of informed consent by their legally acceptable representative.
5. The infant does not have a parent/legal representative who can provide informed consent or consent can not be obtained before 72 hours of age.
In addition, any infant identified by the treating medical team may be excluded from the study at the request of the treating clinician in consultation with the site lead investigator.

Study design

Purpose

Natural history

Duration

Longitudinal

Selection

Defined population

Timing

Prospective

Statistical methods / analysis

The sample size for BLUEPRINT is designed to address the robustness of early respiratory phenotypes identified predicting BPD. The prevalence of survival with bronchopulmonary dysplasia within the Australia and New Zealand Neonatal Network (ANZNN) is 69%. Assuming this bronchopulmonary dysplasia prevalence and a moderate C-index of 0.75 is achievable with a binary logistic regression prediction model with BPD (yes/no) as the outcome, a minimum sample size of 500, 550 and 600 infants was estimated based on 10, 11 or 12 predictor variables respectively (from any domain of clinical, imaging and protein data). We estimate that the predictive model developed in BLUEPRINT may have up to 10-12 predictor variables including several basic clinical and lung imaging covariates and only one to two proteins. This sample size prediction assumes the distribution of births within the 22-25+6-, 26-28+6- and 29-31+6-week GA cohorts as reported in the ANZNN.

Defining the early life respiratory phenotypes: Proteome, lung imaging, clinical and demographic data will be combined to examine longitudinal alterations with ANOVA (multi-comparison), generalised additive models and post-hoc analysis using Perseus/R. Both supervised and unsupervised multivariate approaches including principal component analysis (PCA), Latent Class Analysis, hierarchical cluster analysis and partial least square discriminant analysis (PLS-DA) maybe used to assess i) which clinical/protein/imaging measures tend to cluster at each time-point, ii) how background changes in protein densities, functional imaging and cardiorespiratory measures relate to different clinical treatments.

Development of a biomarker-based BPD risk (and 1- and 2- year) prediction model: We will develop a risk prediction model for BPD diagnosed at 36 weeks, based on a combination of proteins, imaging and clinical measures (minimum 7 inputs) derived within the first 7 days after birth. Model development will include several steps starting with methods for variable selection and model fitting to testing the performance and validation of models. To test measures originally significantly associated with BPD, and identify other measures that are predictive of BPD, binary logistic regression, multiple forward stepwise logistic regression and other classification models will be evaluated with likely measures as covariates. Model performance and discrimination will then be evaluated. Internal validation with both cross-validation and bootstrapping methods to adjust for model over-optimism and bias towards inherent overestimated performance metrics will be applied.

Alternative models of BPD risk will be evaluated using logistic regression and machine learning algorithms.

Recruitment

Recruitment status

Not yet recruiting

Date of first participant enrolment

Anticipated

31/08/2024

Actual

Date of last participant enrolment

Anticipated

30/11/2027

Actual

Date of last data collection

Anticipated

30/11/2029

Actual

Sample size

Target

550

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

The Royal Women's Hospital - Parkville

Recruitment hospital [2]

Monash Children’s Hospital - Clayton

Recruitment hospital [3]

The Royal Childrens Hospital - Parkville

Recruitment hospital [4]

Joan Kirner Women’s and Children’s Hospital - St Albans

Recruitment hospital [5]

Mercy Hospital for Women - Heidelberg

Recruitment postcode(s) [1]

3052 - Parkville

Recruitment postcode(s) [2]

3168 - Clayton

Recruitment postcode(s) [3]

3021 - St Albans

Recruitment postcode(s) [4]

3084 - Heidelberg

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

National Health and Medical Research Council

Address [1]

Country [1]

Australia

Primary sponsor type

Other

Name

Murdoch Children's Research Institute

Address

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

The Royal Children’s Hospital Human Research Ethics Committee

Ethics committee address [1]

http://www.rch.org.au/ethics

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

26/04/2024

Approval date [1]

05/07/2024

Ethics approval number [1]

HREC/107608/RCHM-2024

Summary

Brief summary

Most babies born preterm have breathing problems shortly after birth, and many need help with their breathing. Clinicians have many treatments to help preterm babies breath, and know which treatments works best for most babies. But clinicians don’t know which treatments will work best for each baby. 

The BLUEPRINT Study aims to provide a more precise picture (phenotype) of how a specific preterm baby’s lungs are working in the first 7 days after birth. This will be achieved by combining information on the clinical care being used, measurements of lung function and the pattern of proteins in the blood collected 3 and 7 days after birth. We will then follow babies through until 2 years of age to measure their lung growth and function. By understanding the different lung phenotypes that exist in preterm babies, we hope to help doctors know which treatments may be best for a baby and predict which baby might be at more risk for lung problems as they grow up.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof David Tingay

Address

Neonatal Research, Murdoch Children's Research Institute, 50 Flemington Road, Parkville Victoria 3052

Country

Australia

Phone

+61 393454023

Fax

david.tingay@mcri.edu.au

Contact person for public queries

Name

Merrin Pang

Address

Neonatal Research, Murdoch Children's Research Institute, 50 Flemington Road, Parkville Victoria 3052

Country

Australia

Phone

+61 393457043

Fax

merrin.pang@mcri.edu.au

Contact person for scientific queries

Name

David Tingay

Address

Neonatal Research, Murdoch Children's Research Institute, 50 Flemington Road, Parkville Victoria 3052

Country

Australia

Phone

+61 393454023

Fax

david.tingay@mcri.edu.au

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

Yes

What data in particular will be shared?

All individual participant data collected during the trial, after de-identification and publication of primary results will be available including lung imaging and protein data.

When will data be available (start and end dates)?

3 months after publication of primary results and up to 25 years after publication.

Available to whom?

Researchers who provide a methodologically sound proposal, with approval by an independent review committee (“learned intermediary”). Others who wish to access the data will be assessed on a case-by-case basis at the discretion of the Study Steering Committee.

Available for what types of analyses?

For methodologically sound purposes to achieve the aims in the approved proposal.

How or where can data be obtained?

Proposals should be directed to david.tingay@mcri.edu.au to gain access. Data requestors will need to sign a data access or material transfer agreement approved by the Murdoch Children’s Research Institute.

What supporting documents are/will be available?

Doc. No.	Type	Email	Attachment
22234	Study protocol	blueprint@mcri.edu.au	382577-(Uploaded-09-07-2024-10-02-15)-BLUEPRINT_Protocol_V1.2_30May24_CLEAN.pdf
22235	Ethical approval	blueprint@mcri.edu.au	382577-(Uploaded-09-07-2024-10-02-15)-107608 Ethics 05.07.2024.pdf
22236	Informed consent form	blueprint@mcri.edu.au	382577-(Uploaded-09-07-2024-10-02-15)-BLUEPRINT_HREC Master PICF v1.2 02Jul24_CLEAN.pdf
22289	Data dictionary	blueprint@mcri.edu.au
22290	Statistical analysis plan	blueprint@mcri.edu.au

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

Trial Review

Registering a new trial?

Documents added manually

Documents added automatically