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In instances where subphenotyping is completed the day before randomisation due to delays in receiving the results, which time point should be used to determine the lowest bicarbonate value? Should this be the lowest value recorded in the 24 hours prior to the blood sample being taken, or the 24 hours prior to randomisation?

The lowest bicarbonate value recorded in the 24 hours prior to the blood sample being taken should be used.

Should eGFR or creatinine clearance be used when determining baricitinib dose adjustments?

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.

Is a patient who is requiring renal replacement therapy eligible for simvastatin?

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.

Regarding the ‘high-dose’ steroid exclusion criterion for baricitinib, patients receiving hydrocortisone are excluded. Is there a specific hydrocortisone dose threshold that defines “high dose”?

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, when should blood samples be taken?

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.

Is the courier service available seven days a week?

This may vary between sites. We are working towards providing a seven-day service wherever possible.

If a patient is randomised while not receiving steroids but is subsequently started on steroid after randomisation, how should this be managed?

There are no restrictions on concomitant medications following randomisation. However, the use of other experimental therapies, such as Dex20 in the GUARDS trial, should be avoided. For patients enrolled in PANTHER, steroid use is discouraged. Given the open-label study design, minimising differences in co-interventions between treatment groups is important, as variable steroid use could introduce performance bias.

If a patient is randomised to simvastatin, does clarithromycin have to be stopped?

No, however CK levels would need to be monitored, if CK levels increase, clarithromycin should be stopped. 

 

If a patient is receiving Amiodarone at the point of eligibility assessment can they be randomised to Simvastatin?

No, if the patient is receiving ongoing treatment with Amiodarone then they are excluded from the Simvastatin intervention of PANTHER.

What should we do if a patient is given amiodorone?

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.

Can the cell preservation tube be stored and not processed?

CPT tubes need to be processed. Please do not take this sample if you are unable to process it.

Can BAL samples be stored without processing?

BAL samples can be centrifuged and only the supernatants stored with no other processing or assessment. We would need the centrifugation stage.

We don’t have a 2000g centrifuge. Is 1800g acceptable?

This is fine. If you have a 1800g centrifuge. Please spin the sample for 12 minutes instead of 10.

What studies are you co-enrolling with?

Our co-enrolment list can be found on the documents page under Study Guides, Manuals & Co-enrolment.

What is the available funding for set-up, per patient and close down? 

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.

Is your PANTHER Launch video available to watch?

Yes, please see here.

Will the study be providing the Baricitinib?

No, we will be using ward level stock and managing the costs through the excess treatment costs pathway.

Is there a timeframe that we must randomise the patients?

Yes, within 48hrs of ARDS diagnosis but we encourage you to randomise patients as soon as possible.

Will PANTHER be linked with the API scheme? 

Yes

Will we all have access to a “master” eISF, or dependant on amendment? Will we gain access to the updated documents once an amendment goes through at our site?

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.

Will there be access to the eISF for the duration of the archiving period please? 

Yes

What eISF does PANTHER use?

PANTHER will be using Florence as our electronic ISF, there will be no need to print an eISF.

Which device is being used?

PANTHER will be using the Randox Evidence MultiSTAT device.

What are the dimensions of the device?

585 (H) x 535 (D) x 570 (W) mm

What samples need to be taken?

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.

Will Baricitinib be provided by the sponsor?

No, this will be hospital stock, the costs can be recovered via the excess treatment costs pathway.

How long should Baricitinib be given?

10 Days or until ICU discharge.

Will Simvastatin be provided by the sponsor?

No, this will be hospital stock

How long should Simvastatin be given?

28 Days or until ICU discharge.

Who completes the day 180 follow up calls with the patients?

The central team will complete all follow up calls. Sites are only required to confirm survival status at these time points.

Can ACCPs confirm eligibility?

Yes, they can, but they would need to be listed on the delegation log, as this study is a CTIMP medical oversight is required.

Do clinicians who are confirming eligibility need to be on the delegation log?

Yes, clinicians confirming eligibility should be listed.

Is deferred consent approved for this study?

Yes, if a patient lacks capacity the deferred consent model can be applied. Please speak to next of kin first if possible. Always seek retrospective consent once the patient regains capacity.

Can anyone obtain consent if they are delegated to do so on the delegation log?

Yes, if the PI has delegated the responsibility of taking consent to a doctor or nurse either can obtain consent as long as they are appropriately trained.

Do all pharmacists need GCP or just pharmacists within the clinical trials team set up?

Only those dealing with the drug supply for the trial, the research pharmacist. Other clinical pharmacists in the hospital or ICU do not.

Who can prescribe PANTHER treatments?

Any clinician whose role includes prescribing can prescribe drugs for the trial. They do not need to be listed on the delegation log or GCP trained. However, the study pharmacist, who must be GCP trained and listed on the delegation log will oversee the prescribing for the study.

Do pharmacists need to be GCP trained?

The study (research) pharmacist listed on the delegation log need to be GCP trained. Clinical pharmacists on the wards / ICU do not.

Completed your MMST training?

Fill in the form and send the confirmation email to 
pantheruk@imperial.ac.uk

Completed your eligibility assessor V3.0 training?

Fill in the form and send the confirmation email to 
pantheruk@imperial.ac.uk

Completed your SIV V2.0 training?

Fill in the form and send the confirmation email to 
pantheruk@imperial.ac.uk