Eligibility and Recruitment
Q: Are covid-19 patients eligible?
A: Yes - covid-19 patients who meet all inclusion criteria and do not meet any exclusion criteria should be recruited.
Q: If a patient has a tracheostomy but is not on long-term ventilation, can they be eligible for Oxy-PICU?
A: Yes, if they meet all other inclusion/exclusion criteria they can be recruited.
Q: If an eligible patient is missed initially, successfully extubated but then reintubated during the same admission, are they then eligible?
A: Not if they are outside of the six-hour window for face-to-face contact with PICU staff or transport team. However, if an eligible patient is missed in a PICU admission, is discharged and then admitted/readmitted to PICU at a later date, they may be eligible and should be screened in this new admission.
Q: If a patient is being oscillated or on nitric, should they be excluded?
A: No, please do not exclude these patients. These cases may be particularly helpful in determining whether children who are the most sick receive a greater benefit.
Q: If a patient is being oscillated, would should we input for PEEP?
A: As PEEP will be ≥5 in this case, please use the online randomisation system where the options are ≥5 or <5.
Q: Would patients admitted with seizures be excluded because of the 'brain pathology/injury as primary reason of admission' exclusion criteria?
A: It depends – if seizures are the primary reason for admission and they are still fitting then they meet the exclusion criteria. If the fits have stopped and the reason for admission is drug-induced respiratory depression or respiratory failure from aspiration then they are eligible (provided they need or are thought to need supplemental oxygen). If the patient is randomised because of uncertainty about oxygen targets at the time and then afterwards there is a revision of the history/results to increase the worry about brain injury, then the patient was correctly included in the study. It becomes a clinical decision to follow the allocated treatment but they remain in the study and we treat this as a protocol deviation rather than a withdrawal or randomisation in error.
CRF and MACRO
ICNARC's MACRO User Guide is available below. A video tutorial is available at https://training.icnarc.org/?page_id=118.
Q: Does ‘blood transfusion’ on the CRF Organ Support page refer only to packed red blood cells or should we also include platelets, FFP etc. in this?
A: Blood transfusion in this case refers only to packed red blood cells or whole blood.
Q: If a measurement is taken outside the window, would we rather it was recorded with a note marking the time or instead marked as missing/not recorded?
A: If this is a one-off, please mark as missing/not recorded – however, if it is likely that many measurements will be missed (eg. if some measurements are only taken at specific times on your unit), please record the value taken closest to the time with a note of when it was taken.
Q: Where the CRF asks for PaO2, if the gas is venous or source unknown then should we mark as not recorded?
A: Only PaO2 should be recorded – PvO2 or PcO2 should not be recorded. Please mark as NR if there is no PaO2 measurement.
Q: Where the CRF says ‘date/time of end of all respiratory support’, does this include nasal prongs/humidified oxygen? Or is this only for HFNC and NIV?
A: This includes all support with a machine – including HFNC or NIV – but not for oxygen alone.
Q: Is there a withdrawal form?
A: No - if consent is withdrawn after initially being given, please just note this on the consent form with dates and inform ICNARC. All data collected up to the point of withdrawal or non-consent will be retained in the trial, unless the parent/legal guardian requests otherwise.
Q: When is the ‘date/time of end of all respiratory support’ for patients who have been readmitted to PICU?
A: Please record the last occurrence within 30 days of randomisation (provided it was for at least 48 hours), or the first occurrence if more than 30 days from randomisation.
Q: When do we stop collecting data on CRF/MACRO? Is it once the participant is extubated?
A: Daily/twice daily data should be collected up until PICU discharge (including any time spent in the HDU if there is a separate PICU/HDU). Please continue recording organ support data up to Day 30.
Q: How should phone consent be recorded?
A: Please record phone consent as 'in person' with a note indicating that the consent was over the phone.
Q: Does the >94% target mean 94-100%, or 95-100%?
A: 95-100%. This helps us maintain a clear separation between the groups.
Q: If a patient is enrolled in the study and then develops one of the exclusion criteria (eg. pulmonary hypertension), should they be withdrawn?
A: No. The team may wish to go off protocol if this occurs, depending on whether there is evidential basis for making that decision. We will handle this as a protocol deviation rather than withdrawing the patient.
Q: If a patient is in the conservative group with their peripheral O2 sats being maintained between 88-92% and their PaO2 is then very low, should they be withdrawn from the study if the clinician wants high PaO2?
A: The arterial oxygen content is determined by the SaO2, not the PaO2. There is no evidence base for targeting a high PaO2, so they should definitely stay in the study and we will handle as a protocol deviation as above.
Q: Is there any concern about potentially extubating patients with peripheral O2 sats of 88%?
A: There’s no evidence that this is harmful – in fact, the RSV data suggest lower SpO2 targets accelerate coming off oxygen without harm. The reassurance is that lower targets are likely to mean more rapid weaning down to FiO2 of 0.21 and most often SpO2 above the target range. A target of 88-92% should not stop progress with the vent, but it may be tough to reach this level once things are improved – however, this is fine.
Q: When does the SpO2 target apply?
A: The target applies whenever a patient is invasively ventilated - so not for NIV.
Q: What is the process when a patient is discharged from PICU but then readmitted within 30 days of randomisation?
A: If patient is readmitted to PICU within 30 days of randomisation (regardless if index admission or a different admission), please keep original allocation and continue collecting primary outcome and hourly/twice daily data. (Whenever an Oxy-PICU patient is invasively ventilated, twice-daily data should be collected, and organ support data should be collected up until 30 days from randomisation).
Q: What is the process when a patient is discharged from PICU but then readmitted more than 30 days after randomisation?
A: After 30 days from randomisation, SpO2 target is up to sites. There is no need to continue collecting twice-daily data.
Q: When does trial treatment end?
A: Trial treatment ends at first successful extubation, or at 30 days - whichever is later. This is for safety monitoring purposes.
Q: What is the process for patients transitioning to long-term ventilation?
A: For Oxy-PICU, long-term ventilation is defined as no longer trying to wean. Please record this on the eCRF with a comment. Once this definition is met, there is no need to adhere to the original allocation or collect any further twice-daily data.
Q: How should functional status at discharge be recorded if a patient is admitted and discharged from PICU multiple times?
A: If within 30 days of randomisation, use the last discharge. Otherwise, use the first discharge after 30 days from randomisation.
Q: How are 'final extubation' and 'successful extubation' defined?
A: Final extubation is the first successful extubation. Successful extubation is being extubated for at least 48 hours without reintubation. Date/time of end of all respiratory support should therefore be the end of the last period of support that started during the first 30 days since randomisation, provided it was for at least 48 hours.
Co-enrolment is allowed with the following studies;
– DIAMONDS (and all observational studies)
– BATCH (possibly some interaction in theory but very unlikely, very small if so, and only very indirectly linked to our outcomes)
– BESS in some cases (please email ICNARC to confirm)
For any other studies, please contact the Oxy-PICU team or Mark Peters directly. FAQs and co-enrolment details will be updated periodically.