Yes, as the patient has to meet both exclusions to be excluded from simvastatin:-
If they do not meet both they are eligible
We understand that this can be challenging. The decision should be based on clinical judgement, considering the patient’s overall clinical presentation and whether the hypoxia is consistent with ARDS.
Yes, the patient can still be randomised, provided they are willing to receive standard of care and one of the interventions. They do not need to be willing to receive both interventions to be eligible for randomisation.
Patients must meet all three ARDS criteria within the same 24-hour period to be eligible for recruitment. If a patient meets one criterion but subsequently no longer meets it, they will not be eligible if the other criteria have not also been met within that 24-hour period. Therefore, the patient’s eligibility depends on whether all three ARDS criteria were met within the required timeframe, rather than the X-ray findings alone.
Only one result (either AST or ALT) needs to be collected. If both results are available and one is very high, do not recruit the participant, even if the other result is normal. However, if only one result is available and it is within the acceptable range, the participant can be recruited.
Please use the actual bicarbonate level.
Yes. Patients receiving IMP via the enteral route would be excluded from the Baricitinib intervention.
Telephone consent should be documented as usual patient consent or professional legal representative consent, depending on who provided the consent.
The Aliquot ID can be found on the barcode and follows the format PTXX-XXX-A, with the final letter changing to identify each individual aliquot.
Yes, Hand grip and MMST can be completed 2 days before or after ICU discharge and can be completed 3 days prior to hospital discharge.
No this does not automatically require the study drug to be stopped. The stopping criteria are:
• Serious Adverse Event related to the study drug
• Allergic reaction to IMP
• Decision from the attending ICU physician that the study drug should be discontinued on safety grounds.
• If the investigator considers that a participant’s health will be compromised due to adverse events or concomitant illness that develop after entering the study.
Yes, if your site does not have a -20°C freezer then they can be stored at -30°C.
Respiratory failure should only exclude a patient if it is fully explained by cardiac failure, fluid overload, pulmonary embolism, acute airways disease, or interstitial lung disease. If there is clinical overlap or uncertainty, sites should discuss the case with the trial team.
No. Patients with severe pancreatitis and organ failure should not be excluded on this basis, as they are appropriate candidates for the study.
No. Eligibility should be based on whether the patient meets the ARDS criteria defined in the protocol, including bilateral opacities, respiratory failure not fully explained by cardiac causes or fluid overload, and meeting the required PaO₂/FiO₂ ratio.
Aim to randomise as soon as possible after consent. For minor changes in condition (e.g. a change in P/F ratio), the recommendation is generally to proceed with randomisation. If there is a significant change (e.g. extubated), consider not randomising the patient. The team should use clinical judgement and consider whether the trial treatment would still be appropriate. If unsure, please contact the trial team via pantheruk@imperial.ac.uk.
The 48-hour window starts when the final eligibility criterion is met and allows time for consent and phenotyping. Randomisation takes place once the phenotype result is available. This allows for occasional delays in treatment initiation, reflecting routine clinical practice.
No, only patients who have ARDS should be added.
Sites should obtain patient consent within 48 hours of ARDS diagnosis. The 48-hour clock starts when the third ARDS criterion is met.
The SOFA score components should be taken from the previous 24hrs and not 8am.
The lowest bicarbonate value recorded in the 24 hours prior to the blood sample being taken should be used.
Dose adjustments for baricitinib should be based on eGFR, not creatinine clearance. eGFR is universally reported, aligns with other major clinical trials, and this approach has been approved by the MHRA.
Yes. The exclusion criterion is severe renal impairment (eGFR <30 mL/min) in patients who are not receiving renal replacement therapy. Patients who are requiring or receiving renal replacement therapy remain eligible. This also applies if there is a temporary break in renal replacement therapy.
The protocol allows up to 200mg hydrocortisone （ie hydrocortisone 50mg 6 hourly is allowed and excluded those receiving more than 200mg hydrocortisone or an equivalent amount of a different steroid
If the laboratory is closed, sampling can be performed on the next working day when the laboratory reopens. This is acceptable provided that sample collection takes place within the 48-hour recruitment window. Consent should be obtained as soon as possible.
This may vary between sites. We are working towards providing a seven-day service wherever possible.
There are no restrictions on concomitant medications following randomisation. However, the use of other experimental therapies such as high dose steroids should be avoided for patients enrolled in PANTHER. Given the open-label study design, minimising differences in co-interventions between treatment groups is important, as variable steroid use across intervention and usual care groups could introduce performance bias. Co-enrollment with trials studying high dose steroids eg dexamethasone 20mg in GuARDS is allowed depending on the intervention eg simvastatin is allowed but baricitinib is not.
No, however CK levels would need to be monitored, if CK levels increase, simvastatin should be stopped.
No, if the patient is receiving ongoing treatment with Amiodarone then they are excluded from the Simvastatin intervention of PANTHER.
If a single dose of amiodarone (single intravenous bolus or any enteral dose) is administered no change is required for the simvastatin dose. However, if a patient receives more than a single dose of amiodarone, simvastatin dose should be reduced to 20mg daily.
CPT tubes need to be processed. Please do not take this sample if you are unable to process it.
BAL samples can be centrifuged and only the supernatants stored with no other processing or assessment. We would need the centrifugation stage.
This is fine. If you have a 1800g centrifuge. Please spin the sample for 12 minutes instead of 10.
Our co-enrolment list can be found on the documents page under Study Guides, Manuals & Co-enrolment.
A combined fee of £279 per patient to cover all costs. If your sites finance requires a more broken-down payment structure, we can make the necessary adjustments.
Yes, please see here.
No, we will be using ward level stock and managing the costs through the excess treatment costs pathway.
Sites should aim to randomise within 48 hours from ARDS diagnosis. However, this can be extended if the sub-phenotyping results take longer than expected.
Yes
Your site will have access to a personal eISF once activated. The trial master file will be maintained by the sponsor team. When an amendment is approved, we will have this sent through to your sites eISF inbox for review and you will file it away.
Yes
PANTHER will be using Florence as our electronic ISF, there will be no need to print an eISF.
PANTHER will be using the Randox Evidence MultiSTAT device.
585 (H) x 535 (D) x 570 (W) mm
Only the initial blood sample for the stratification of patients into their subphenotypes is compulsory. The rest are optional, please see the sampling guide for further information.
No, this will be hospital stock, the costs can be recovered via the excess treatment costs pathway.
10 Days or until ICU discharge.
No, this will be hospital stock
28 Days or until ICU discharge.
The central team will complete all follow up calls. Sites are only required to confirm survival status at these time points.
Yes, as the patient has to meet both exclusions to be excluded from simvastatin:- If they do not meet both they are eligible
We understand that this can be challenging. The decision should be based on clinical judgement, considering the patient’s overall clinical presentation and whether the hypoxia
Yes, the patient can still be randomised, provided they are willing to receive standard of care and one of the interventions. They do not need
Patients must meet all three ARDS criteria within the same 24-hour period to be eligible for recruitment. If a patient meets one criterion but subsequently
Only one result (either AST or ALT) needs to be collected. If both results are available and one is very high, do not recruit the
Please use the actual bicarbonate level.
Fill in the form and send the confirmation email to
pantheruk@imperial.ac.uk
Fill in the form and send the confirmation email to
pantheruk@imperial.ac.uk
Fill in the form and send the confirmation email to
pantheruk@imperial.ac.uk