Condition category
Neonatal Diseases
Date applied
13/08/2010
Date assigned
15/09/2010
Last edited
25/04/2014
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Contact information

Type

Scientific

Primary contact

Prof Samir Gupta

ORCID ID

Contact details

Professor of Neonatology
Deputy Director
Research & Development
University Hospital of North Tees
Hardwick
Stockton-on-Tees
TS19 8PE
United Kingdom
samir.gupta@nth.nhs.uk

Additional identifiers

EudraCT number

2013-005336-23

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Outcome after Selective early Closure of patent ductus ARteriosus (PDA) in extreme preterm infants: a randomised controlled trial

Acronym

Baby-OSCAR

Study hypothesis

Current hypothesis as of 10/04/2014:
To determine if the selective treatment of confirmed large PDAs in extremely preterm babies with ibuprofen within 72 hours of birth reduces the incidence of death or bronchopulmonary dysplasia (BPD) at 36 weeks postmenstrual age.

Previous hypothesis:
Early echocardiographic screening and targeted treatment of a PDA that fails to constrict spontaneously (LARGE PDA) will result in reduced incidence of death/chronic lung disease at 36 weeks and eventually less death/neurodevelopmental disability at 2 years corrected age.

On 10/04/2014 the following changes were also made to the trial record:
1. The acronym was changed from 'OSCAR' to 'Baby-OSCAR'
2. The study design was changed from 'Double-blind randomised placebo-controlled multicentre trial' to 'Multicentre randomised placebo-controlled trial'
3. The anticipated start date was changed from 10/04/2011 to 01/07/2014
4. The anticipated end date was changed from 09/04/2016 to 30/12/2020
5. The target number of participants was changed from 512 to 730
6. The public title was changed from 'Does selective early treatment of foetal shunt (patent ductus arteriosus) in extreme preterm infants reduce the complications and improve their long term outcome?' to 'Does selective early treatment of patent ductus arteriosus in extreme preterm infants reduce the complications and improve their long-term outcome?'

Ethics approval

Nottingham 2 Research Ethics Committee – approval pending

Study design

Multicentre randomised placebo-controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Will be available on trial website once approval has been given by the REC

Condition

Patent Ductus Arteriosus (PDA)

Intervention

Current interventions as of 10/04/2014:
This trial is intending to treat infants in the same window as the prophylaxis trials using ibuprofen with recommended doses as per study protocol. Patients will be randomised (1:1 ratio) to receive study medications or placebo, intravenously. Study medication will be provided as a clear sterile preservative-free solution for intravenous injection. An initial dose of 10 mg/kg will be followed by two doses of 5 mg/kg at 24 and 48 hours apart. The solution of ibuprofen is provided at a concentration of 10 mg/ml in a 5 ml single-use vial, thus 1 ml/kg, followed by two administrations of 0.5 ml/kg, will be required.

Previous interventions:
This trial is intending to treat infants in the same window as the prophylaxis trials using ibuprofen with recommended doses as per study protocol. Patients will be randomised (1:1 ratio) to receive study medications or placebo, intravenously.

The previous sponsor for this trial (up to 10/04/2014) was:
North Tees and Hartlepool NHS Foundation Trust (UK)
University Hospital of North Tees
Hardwick
Stockton-on-Tees
TS19 8PE
United Kingdom
The current address can be found in the sponsor section below.

Intervention type

Other

Phase

Not Applicable

Drug names

Primary outcome measures

Current primary outcome measures as of 10/04/2014:
The primary outcome is defined as a composite outcome of death or BPD at 36 weeks post-menstrual age. BPD is defined as the need for respiratory support and/or oxygen for 28 days or more and at 36 weeks post-menstrual age. The need for oxygen is subjective and hence oxygen dependency will be confirmed using an ‘oxygen reduction test’. This is based on whether the baby is able to maintain oxygen saturations over 90% for 1 hour whilst breathing air. Babies unable to achieve this will be considered to be oxygen dependant.

Previous primary outcome measures:
Death or severe neuro-developmental disability at 2 years corrected age.
The Bayley's scale of infant development III will be used to assess outcomes.

Secondary outcome measures

Current secondary outcome measures as of 10/04/2014:
Secondary outcomes are divided into short- and long-term outcomes:
1. Short-term outcomes:
1.1. Death before discharge
2. Incidence or duration of the following up to time of neonatal unit discharge:
2.1. Severity of BPD at 36 weeks postmenstrual age
2.2. Severe IVH (grade 3/4 with ventricular dilation or intraparenchymal bleeding)
2.3. Cystic periventricular leukomalacia (PVL)
2.4. Retinopathy of prematurity (ROP) requiring treatment
2.5. Pulmonary haemorrhage
2.6. Pulmonary hypertension
2.7. NEC definitive and/or complicated (Bell stage II and above) confirmed by radiology or histopathology
2.8. NEC requiring surgery
2.9. Gastrointestinal bleeding within 7 days of the first dose of study drug administration
2.10. Spontaneous intestinal perforation
2.11. PDA closure at 3 weeks of age (or hospital discharge, if discharged before this age)
2.12. Medical rescue treatment with a COX inhibitor of a symptomatic PDA
2.13. Administration and duration of inotropic support
2.14. Duration of mechanical ventilation
2.15. Total duration of respiratory support (ventilation + nCPAP/high flow oxygen therapy)
2.16. Discharge home on oxygen
2.17. Duration of initial hospitalisation (birth to neonatal unit discharge home)
2.18. Postnatal steroid use
2.19. Safety and tolerability of ibuprofen treatment
2.20. Number of doses of trial medication received during intervention period
3. Secondary long-term clinical outcomes assessed at 2 years of age corrected for prematurity
3.1. Survival without moderate or severe neurodevelopmental disability
3.2. Individual components of survival without moderate or severe neurodevelopmental disability (in the four domains of motor, cognitive, hearing and visual function)
3.3. Survival without respiratory morbidity
3.4. A cost-effectiveness analysis will be conducted of deaths and BPD events avoided and national health services used up to 2 years of age corrected for prematurity

Previous secondary outcome measures:
1. Mortality
2. Complications of prematurity
3. Cardiovascular effects
4. Respiratory outcomes
5. Acute abdominal problems
6. Side effects of medicine
7. Length of hospital stay
8. Developmental outcome at 2 years

Overall trial start date

01/07/2014

Overall trial end date

30/12/2020

Reason abandoned

Eligibility

Participant inclusion criteria

Current inclusion criteria as of 10/04/2014:
1. Born at 23+0 to 28+6 weeks of gestation
2. Less than 72 hours old
3. Confirmed by echocardiography to have a large PDA which is at least 1.5 mm in diameter (determined by gain optimised colour Doppler) AND has unrestrictive pulsatile left to right flow
4. The responsible clinician is uncertain about whether this baby might benefit from treatment to close the PDA
5. Written informed consent has been obtained from the parent(s)

Previous inclusion criteria:
1. Preterm infants born between 23+0 and 28+6 weeks gestation
2. Echocardiographic assessment within 24 hours of birth meeting the enrolment criteria
3. Signed parental consent

Participant type

Patient

Age group

Neonate

Gender

Both

Target number of participants

730 infants

Participant exclusion criteria

Current exclusion criteria as of 10/04/2014:
1. No realistic prospect of survival
2. Severe congenital anomaly
3. Structural heart disease requiring treatment
4. Other conditions that would contraindicate the use of ibuprofen (clinically significant intracranial or gastrointestinal haemorrhage, coagulopathy, thrombocytopenia [platelet count <50,000], renal failure, pulmonary hypertension, known or suspected necrotising enterocolitis [NEC])
5. Antenatal exposure to cyclo-oxygenase (COX) inhibitors
6. Received indomethacin, ibuprofen or paracetamol administration after birth

Previous exclusion criteria:
1. Baby clinically unstable and not expected to survive
2. Congenital anomalies predicted to influence neurodevelopmental outcome
3. Structural heart disease
4. Contraindication to use of ibuprofen (platelet count <50,000)
5. Unlikely to commence first dose of treatment by 24 hours of age

Recruitment start date

01/07/2014

Recruitment end date

30/12/2020

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Professor of Neonatology
Stockton-on-Tees
TS19 8PE
United Kingdom

Sponsor information

Organisation

University of Oxford (UK)

Sponsor details

Clinical Trials and Research Governance Team (CTRG)
Joint Research Office
Block 60
Churchill Hospital
Old Road
Headington
Oxford
OX3 7LE
United Kingdom
ctrg@admin.ox.ac.uk

Sponsor type

University/education

Website

Funders

Funder type

Government

Funder name

NIHR Health Technology Assessment Programme - HTA (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes