FAQs
Click on the links below to find answers to your questions; alternatively you can download the document here.
All of the information about specific trials procedures can also be found on our guidance sheets, which are available to download here:
https://www.npeu.ox.ac.uk/baby-oscar/information-for-hospitals/neonatal-staff
- Where is the Baby-OSCAR trial taking place?
- Where is our nearest recruiting site?
- What are the guidelines for who has to complete GCP?
- Who can sign consent?
- Can participants be enrolled into Baby-OSCAR and another study?
- Baby-OSCAR IMP FAQs
- What to do if a baby transfers?
- Where can I view a copy of the Case Report Forms (CRF's)?
- Do we have a CRF/ guideline for the Oxygen Reduction Test so it is easier for the clinical staff to complete?
- Continuing Care Site FAQs
Where is the Baby-OSCAR trial taking place?
Baby-OSCAR started with a small pilot of 5 sites in 2015 and will launch the main phase later this Winter 2016/2017 in approx. 30 sites across the UK.
Where is our nearest recruiting site?
Details of recruiting sites with NHS permission and continuing care sites already with permission, can be found at https://www.npeu.ox.ac.uk/baby-oscar/centres
What are the guidelines for who has to complete GCP?
According the MHRA Grey Guide, each person involved in a Clinical Trial must receive some training in GCP commensurate with their roles and responsibilities e.g. recording/causality of adverse events, documentation of activities in source notes, or CRF’s, escalating any issues they may identify as appropriate. This will also need to meet the local R&D requirements.
Consent taking:
As long as the person taking consent is:
- GCP trained, and
- on the delegation log, and
- is familiar with the study e.g. eligibility, procedures, potential risks and benefits
Then they can consent the parent(s).
Eligibility:
As Baby-OSCAR is a CTIMP, eligibility must be confirmed by a doctor if consent is taken by a nurse. This must also be documented in the notes. In addition question 16 on Form 1: Trial Entry, asks for confirmation of this.
Prescribing:
Prescribing by a nurse or pharmacist will depend on local practice – as long as they meet local conditions i.e. supplementary prescribers to prescribe and administer prescription-only medicines.
The responsibility should be documented in the delegation log and the approval for supplemental prescribing should be maintained in the training files.
Administering imp/management of the participant:
Since this is similar to standard care in terms of treating a PDA with ibuprofen, then the administering of the IMP will be dependent on:
- local practice
- whether the person is familiar with the study e.g. eligibility, procedures etc.
Safety reporting:
A study physician (investigator) is responsible for reviewing a serious adverse event and considering whether the event was related to the study drug(s).
A physician, who is not a member of the study team, may offer an opinion as to whether the event was related to the study drug(s) and this opinion should be documented in the participant’s medical records.
Who can sign consent?
The consent form can be signed by the mother, or by the partner having parental responsibility for the baby e.g. married to, or in civil partnership with the mother at the time of birth.
Where the father signs, the birth mother must always countersign the consent form as soon as possible and before the baby is discharged. This is because we ask for some maternal data, which will help us ‘flag / trace’ the baby through the Health and Social Care Information Centre (HSCIC), (or named derivative), and other central UK NHS bodies.
Can participants be enrolled into Baby-OSCAR and another study?
Possibly. Please contact the Baby-OSCAR Coordinating Centre to discuss involving infants in Baby-OSCAR and any other study.
Co-recruitment has been agreed for the following trials:
- ELFIN, (A multi-centre randomised placebo-controlled trial of prophylactic enteral lactoferrin supplementation to prevent late-onset invasive infection in very preterm infants) ISCTRN: 88261002 led by the NPEU CTU
- PREVAIL, (PREVenting infection using Antimicrobial Impregnated Long lines) ISCTRN: 81931394 led by the Medicines for Children Clinical Trials Unit, University of Liverpool.
Infants cannot be co-recruited into:
- Minidex, (The efficacy and safety of very low dose dexamethasone used to facilitate the extubation of ventilator dependent preterm babies who are at high risk of bronchopulmonary dysplasia) ISCTRN: 81191607 led by the NPEU CTU
- Tinn2 (Treat Infection in NeoNates 2) led by the French National Institute for Health and Medical Research
Baby-OSCAR IMP FAQs:
Refer also to Guidance Sheet 3: Intervention
How do I calculate doses & administer?
What do I report from a safety point of view?
Why are there different brands of ibuprofen being used?
What temperature should the packs be stored at?
What happens if the packs the temperature goes above 30 degrees?
We have received stock of Baby-OSCAR IMP, what do I do?
What is procedure for delayed doses?
What is procedure for doses not given?
Is open-label treatment permitted?
What is the intervention?
Ibuprofen will be provided as a clear sterile 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 after the initial dose. The solution of ibuprofen is provided at a concentration of 5 mg/ml in a single-use 2 ml ampoule, thus 2 ml/kg, followed by two administrations of 1 ml/kg will be required.
What is the placebo?
Placebo will be supplied as a clear sterile solution of 0.9% Sodium Chloride for injection. The solution will be indistinguishable from that of ibuprofen. It will be given as a 2 ml/kg infusion followed by two infusions of 1 ml/kg at 24 and 48 hours.
How do I calculate doses & administer?
Doses to be calculated on birth weight and administered as a short infusion over 15 minutes, preferably undiluted. If required the IMP can be diluted to appropriate volume with 5% glucose or 0.9% Sodium Chloride and first dose administered soon after randomisation, after 6 hours of age and within 72 hours of birth.
What do I report from a safety point of view?
Safety reporting as described in this section for the baby will be monitored from first dose until 7 days after trial medication. If listed as ‘Foreseeable’ in safety section of protocol, record on the data collection forms accordingly. If ‘Unforeseeable’, report with 24 hours of first knowledge of the event. SARs’ are to be reported up until 7 days after last dose of trial medication.
Why were different brands of ibuprofen used in the pilot study and main trial?
NeoProfen® was used only for the pilot phase and will not be used in the main trial.
Version 4 of the protocol, relates to NeoProfen®, the active drug used for the pilot - a formulation of
ibuprofen lysine (approved by the US FDA in 2006) for the treatment of PDA was unlicensed for use within the EU. The licensed alternative, Pedea® was unavailable during the pilot phase.
NeoProfen® was used under the notification of intention to import ‘the medicines for human use
(manufacturing, wholesale dealing and miscellaneous amendments) regulations (SI 2005/2789).’ the formulations are non-equivalent; however, the recommended posology is identical.
Version 6 of the protocol references Pedea®, including the updated safety profile and reference safety information.
What temperature should the packs be stored at?
Packs need to be stored at 30 degrees and below, which is similar to ELFIN, another CTIMP being led by the NPEU CTU. It would be acceptable to store both IMPs in the same location, in a locked cupboard, using the ELFIN thermometer to record daily temperatures and check that there are no temperature excursions above 30 degrees, or at freezing.
What happens to the packs if the temperature goes above 30 degrees, or at freezing?
If you experience any temperature excursions, please refer to Guidance Sheet 3: Temperature, storage monitoring and thermometer use, and phone the office.
- The local research team (including the PI) and clinical trials pharmacist/team at the site should be informed of the excursion.
- The excursion should be documented on a temperature log and a Temperature Deviation/Quarantine Form (found in document box) completed.
- The affected stock of IMP should be immediately quarantined by placing in a bag and attaching a copy of the Temperature Deviation/Quarantine Form.
If possible, the IMP should be moved to the pharmacy, or another secure area where storage requirements can be met.
We have received stock of Baby-OSCAR IMP, what do I do?
Effective control of stock is only possible if pack delivery and movement is logged onto the Baby-OSCAR website accurately and promptly.
You may not be able to randomise a baby because the packs are not recorded as being received in either the Pharmacy, or NICU.
Please refer to Guidance Sheet 3(a): Trial intervention stock control.
A member of the pharmacy team:
A member of the pharmacy team will need to log onto the web-based pack management system and receipt the packs. The username and passwords are available on request, but should be contained within your ‘Pharmacy Site File’.
You will need to select ‘login packs at pharmacy’ and follow the on-screen prompts.
NICU team:
A member of the research team will need to log onto the web-based pack management system and receipt the packs at NICU. The username and passwords are available on request, but should be contained within the ‘Investigator’s Site File’.
You will need to select ‘login packs at NICU’ and follow the on-screen prompts.
What do I do about documentation if I drop an ampoule of the IMP, or I don’t use it after making it up?
Note the loss of the ampoule on the ‘IMP Accountability Log, Recruiting Centre’ in the ampoule spoilt/wasted column. If the dose has not been given at all, document ‘not used’ on the ‘IMP Accountability Log, Recruiting Centre’.
Please refer to Guidance Sheet 3(C): Reconciliation of trial intervention.
What is procedure for delayed doses?
The 2nd and 3rd dose can be delayed based on clinical practice. For the purposes of the trial, please assume the IMP to be Ibuprofen, and take the clinical action locally practiced, with the use of Ibuprofen.
We have not been prescriptive and have not defined duration to with-hold further doses.
If you look at section 7.9 of protocol (version 5), we have mentioned when to stop trial medication and given an example of oliguria (urine output <0.6ml/kg/hr) and significant bleeding which are definitive indications for stopping IMP.
For serum creatinine levels, please refer to [the paper] - Thayyil et al. J Perinatol 2008;28:226-229.
When looking at the platelet count, use the cut-off given in the exclusion criteria of <50,000, as this cut off could also apply when considering subsequent doses.
Administer the next dose as soon as possible when deemed suitable to do so.
What is procedure for doses not given?
Document the dose not given on Form 2 – Trial Intervention section B and state the reason, and on the infant’s drug chart in the Trusts agreed method of documenting non administration of medicines.
Is open-label treatment permitted?
Responsibility for the care of the baby will remain fully with the neonatal clinical team irrespective of the trial.
Open-label treatment (both medical and surgical) is permitted within the protocol if the following minimum criteria are met and other medical management strategies have been tried. Surgical treatment however should only be considered if the PDA remains persistently large after one course of treatment with a COX inhibitor or in circumstances where medical treatment may be contraindicated or time does not permit medical open-label treatment first.
- Inability to wean on ventilator (ventilated for at least 7 days continuously) and any of: inability to wean oxygen; or, persistent hypotension; or, pulmonary haemorrhage; or, signs of cardiac failure
AND
- Echocardiographic findings of a large PDA (PDA ≥ 2.0 mm with pulsatile flow)
AND
- Echocardiographic findings of hyperdynamic circulation or ductal steal (refer to Baby-OSCAR ECHO workbook).
All open-label treatment will be administered in an open fashion.
A persistent open PDA requiring open-label treatment (medical or surgical) should be reported to the Trial Co-ordinating centre using Form 5: Open Treatment of PDA.
What to do if a baby transfers?
If a baby transfers:
- Phone the NPEU Co-ordinating Centre to inform them of the transfer (they will check for approvals)
- If appropriate; Carry out a 3 week ECHO scan and complete Form 3. Form 3 to be completed around 3 weeks of age, or last ECHO after completing trial medication prior to transfer, or death, or discharge if sooner
- Carry out a 36 week ‘Oxygen Reduction Test’. Complete Form 4, OR record on the transfer envelope the date the test is due
- Complete Form 6: Baby Outcomes - in Section C, make sure you complete tab ‘B’ only
- If appropriate: Give the last dose possible of IMP – no doses will be administered at the continuing care site.
Where can I view a copy of the Case Report Forms (CRF's)?
The CRF's can be found on our web page:
https://www.npeu.ox.ac.uk/baby-oscar/information-for-hospitals/data-collection-forms
Do we have a CRF/ guideline for the Oxygen Reduction Test so it is easier for the clinical staff to complete?
The Oxygen Reduction Test at 36 weeks, for babies whose oxygen requirements are <30% and not receiving respiratory support, is when the baby is around 36 weeks’ of gestation.
Weaning a baby on oxygen is something that you may do automatically on the ward, but not necessarily document it.
The test is not difficult or time consuming, and can be easily followed using the flow diagram displayed in the protocol and on the front page of Form 4.
The local research team at the (original) recruiting site will be able to advise on carrying out the test, or contact the NPEU CTU to arrange for a medically qualified colleague to talk you through the test if required.
Continuing Care Sites:
Is a Continuing Care Site (CCS) responsible for administering the IMP?
No, babies are mostly dosed within the first week of birth. We anticipate that ongoing pharmacy involvement will no longer be the case, and there is no expectation to transfer the IMP with the baby.
Is a CCS responsible for entering a baby into the study or seeking parental consent?
No, these activities, along with administering all of the doses, take part at a recruiting site.
Is there any clinical support for a CCS?
The Baby-OSCAR nurse will be responsible for liaising with the continuing care site, ensuring the PI identified fully understands the trial and, for establishing and maintaining an audit trail for the movement of each transferring baby.
