The study (research) pharmacist listed on the delegation log need to be GCP trained. Clinical pharmacists on the wards / ICU do not.
The study pharmacist should be listed on the delegation log, and GCP trained. This pharmacist can oversee the prescribing for the study but the prescribing clinicians do not need to be listed on the delegation log or GCP trained.
Only those dealing with the drug supply for the trial, the research pharmacist. Other clinical pharmacists in the hospital or ICU do not.
As this is a clinically approved drug (used in routine practice), the administers of the drug are not required to be on the delegation log or GCP trained.
Staff should still receive appropriate medication training for Baloxavir. For instance, this drug is NOT given daily due to its longer half life.
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.
Yes, this was more relevant for ICUs but if a ward patient lacks capacity the same deferred consent model can be applied. Please ensure the patient has the opportunity to consent and speak to NOK first if possible. Always seek retrospective consent once the patient regains capacity.
Yes, we have designed the consent forms so that you can remove domains/interventions that your site is not participating in, and we can also remove treatments once they are no longer available.
Yes, clinicians confirming eligibility should be listed.
Yes, they can, but these would need to be listed on the delegation log, as this study is a CTIMP medical oversight is required.
Yes, and we have taken the opportunity to streamline these too so hopefully they are easier and simpler to use.
The lead PI can sign off the Sub-I’s
No, a new site would be defined as a new site contract. If a current contract with a Trust stands and a department is added this is considered in addition to the current site and not a new site.
For new sites we will provide new contracts but for existing sites we will generate variations/appendix as needed including the new funding arrangements.
The new site set up fee covers contract negotiations and pharmacy checks, therefore if a site is already open and moving into the ward a site set up fee would not apply.
There is an additional site fee for existing sites when they expand to the new influenza domains.
Yes, this is available on our website in documentation > study tools
Yes, please see our website, we have training slides, the webinar recordings and training logs.
Yes, you can focus on ICU only. We would encourage sites to expand to wards as many patients with flu are going to be on the ward and treating early is likely to be most effective. If not practical let us know.
Yes, REMAP-CAP can co-enrol with any observational studies
Yes, we can co-enrol with MARCH
The site teams complete these calls for influenza patients, the time for this was factored in to the SoECAT and the per patient fee.
No, we do not currently have translations of these. We are looking into developing these and will inform sites in the future once they are available.
The sponsor and REMAP-CAP team are currently updating the monitoring plan and will provide an update as soon as confirmed.
Update: ICU, wards and paeds will be monitored separately. Unless it is easier for the site to join these visits.
We will only ask for information as described in the patient information sheet to be provided on the database. This does not include the patients address or next of kin.
We do not have a set timeframe for this. We rely on the site’s professional judgement on the number of times they deem appropriate to reach out to the patient or family member. We ask that you make sure you document all attempts/ conversations that are had around consent.
The timeline should be tracked from the date of admission.
There are still unanswered questions regarding the effects of immune modulators in flu. We encourage sites to continue randomising patients so that we can gather more data and improve our understanding.
We keep the patient in the study but raise a protocol deviation
We are not mandating sites to ringfence stock for your business-as-usual hospital clinical stock, pharmacists may choose to do this as part of their processes, but we are not mandating this.
For drug stock supplied specifically for REMAP-CAP e.g. baloxavir, this does need to be ring-fenced for the trial
This is not mandatory, however if your site does run tests for subtypes this could be helpful and so please do enter the subtype if known on the eCRF.
No, please only include patients who are acutely unwell due to influenza not incidental cases.
The whole platform is CAP rather than influenza, but we are focusing on influenza this winter. Only influenza patients are included from the ward right now.
Severe state = patient is in ICU AND receiving respiratory and/or support.
Moderate state = all other patients (including in ICU receiving no cardio or respiratory support & all patients not in ICU)
No, patients can only be randomised in each domain once.
If they are randomised to a domain in a moderate state and later move to severe state and are now eligible for a new severe state domain they can be randomised to this new domain as this is a different domain.
This is possible with the current corticosteroid domain but we are focusing on recruiting patients with flu on the ward at this time.
No, the patient must be acutely unwell because of flu
No, patients must be balanced at each site for the analysis, we cannot adjust for individual patients and so you must decide which interventions are available for all patients and not select per patient.
Yes, as long as they are being admitted to hospital. The earlier the better but they will need to be flu positive which is not always known while in ED. But currently we realise patients could spend a long time in ED
Once the patient is randomised, this is day 1. Prior to randomisation is baseline
Any level, there is no set criteria. They would be eligible even on low flow oxygen in the steroid domain.
It is not a specific exclusion to the platform but would be for individual interventions
For ICU patients, we have the two doses of steroids or the shock only intervention. If your ICU believes it to be unacceptable to give steroids in these patients with shock you can just select the interventions which work best for you.
The updated pharmacy manual can be found on the documentation page of this website in the pharmacy folder
There are two responses to this:-
1. There is uncertainty about evidence for Tamiflu (oseltamivir) in hospitalized patients and certainly no RCT evidence to support its use. Therefore we encourage randomisation including no-antiviral treatment so that we learn if it is useful or not in this population
2. If the site does not have equipoise for the ‘no oseltamivir’ intervention, the site can still participate in this treatment option but select 5 days and 10 days and not the ‘no oseltamivir’ option.
There is limited evidence in this area, based on the evidence we have provided one suggested dose from a previous RCT, as a guide. As per the DSA please follow your standard practice in the first instance.
No, as this is a short course no need for weaning, it can just be stopped after the course is completed.
The patient would be excluded from the antiviral domain as they have already been treated with an anti-viral drug.
No, you can use any formulation you would usually use, capsules, suspension or capsule contents dissolved in water.
No, these do not require any trial specific labelling as they are used in routine clinical practice.
It is not required to send the patient home with treatment to finish the course. If you choose to do so, please ensure the correct course duration is provided i.e. no more than 5 or 10 days depending on the allocation
Baloxavir will be provided by Roche for free to sites. Sites can request the order form from the ukremap-cap@icnarc.org address. Sites must be open to the antiviral domain before ordering.
The dosing information in the DSA is provided as guidance, sites can choose to follow their local policy if they wish as long as they give the dose over the correct duration
Accountability is required at pharmacy level on inventory/accountability logs, but not at ward level.
Baloxavir that has been dispensed for a patient does not have to be returned from wards to pharmacy for counting or logging on an accountability log – these should be disposed of by the research team on the ward as they would for other drugs used in the clinical areas. If pharmacy have any unused or expired Baloxavir, pharmacy should email ukremap-cap@icnarc.org for permission to destroy then file a copy of the destruction certificate in the pharmacy site file.
Hospitalised patients are classed as ‘complicated influenza’ and therefore we recommend a second dose. Baloxavir has a half life of 79hrs. Therefore if the patient is still unwell on day 4 give another dose, if not and has been discharged home, do not give a dose on day 4.
This is at local clinical discretion. In previous trials if the patient is still unwell a third dose on day 7 has been given.
Yes, this is fine as long as the patient does not exceed the randomized duration i.e., no more than 5 days or 10 days depending on the intervention.
This is now available as part of the immune modulation domain. If your site is interested in taking part in this domain, please contact ukremap-cap@icnarc.org
Yes, this is fine. Please make sure that it is kept in a secure location and that doses are only given on the correct days.
The recommendation is to avoid concomitant administration because of the risk of complex formation between baloxavir and bivalent cation in the GI tract, which may reduce the absorption. Ideally, morning vs evening administration would be good; if not possible 4-5h apart.
If the first dose of Baloxavir (Day 1) is missed, it should be given on Day 2 and a protocol deviation must be logged in the database.
Consequently, the second dose (originally scheduled for Day 4) should also be moved by one day and given on Day 5. Both adjustments can be recorded under the same protocol deviation in the database.
Only nasal swabs are required as part of the influenza stratum. These will be provided to your site once open, with pre-packaged safe boxes for return.
Swabs are sent out to sites on a weekly basis
Yes, the information we obtain from the swabs are not part of our primary outcome. Please do continue to recruit patients before the swabs arrive.
Swabs can be stored at room temperature.
Up to 5 days. We therefore suggest sites to send them back to us twice a week. If they have one patient, please collect day 1 and day 3 samples and then send them back.
Please take the swab as close to the timepoint as possible. If you miss the timepoint, please take the swab ASAP afterwards and enter the correct date. Alternatively take the swab up to 24 hours early
PICU admission time, as the difference is not likely to be many hours.
Adults tend to stay longer than children, and this was designed with adults in mind initially, there are some patients who do spend longer time in hospital, if you don’t want to participate in 10 day arm and prefer to just participate in the 5 day arm, this is fine
Due to the lack of availability of ORA-Blend please only include severe patients (with NG tube) in the baloxavir intervention for now
Roche has provided instructions and this will be made available to sites. Essentially disperse one tablet in 100mL and give the required volume.
As above, please only randomise severe patients (in ICU) to baloxavir for now due to the volume issue.
At the moment yes, for patients on the ward or that have fluid restrictions please exclude these from baloxavir at the moment due to the volume issue. We hope that by next winter we will have a solution for this.
Inhaled zanamivir is not permissible as per the protocol. If the clinician plans to give zanamivir to the patient as is immunocompromised for example then the patient should be excluded for the following reason ‘not in best interest to randomise patient’
If you intend to give the patient steroids they would not be eligible to be randomised to that domain.
We advise that you use the same preparations as you would for patients with COVID-19.
Yes, we have provided guidance in case you do not have a local policy
Please follow the DSA in the first instance, the pharmacy manual provides more detail but the information is the same
Our eCRF has been updated for paediatric patients both the pSOFA and ICU PIM3 score are applicable.
It is uncommon that we detect flu virus in this way and so we need to be pragmatic about this, if the patient has and requires treatment for flu then include them in the study.
Anyone aged 12+ in REMAP-CAP is classed as an adult for analysis purposes
