836 patients have now been recruited to RECOVERY-RS. We would like to say a huge thank you to our recruitment sites, patients and their families for helping us to reach this milestone. These are very challenging times and we appreciate all of your hard work. Recruitment has been exceptional over the Christmas period with over 250 patients recruited in the last month alone. We look forward to our next interim analysis taking place soon and thank sites for your hard work with data collection.

We wish to provide clarification regarding the Safety Reporting requirements for the RECOVERY-RS Trial and notify you of the updated Data Collection CRF.

When assessing whether to record Adverse Events (AE’s) on the e-CRF, please only capture events that are CLEARLY RELATED (i.e. are suspected to have been caused by the administration of CPAP or HFNO). The list below are examples of SAEs that can be caused by non-invasive ventilation. This list is not exhaustive so any other event that has a potential causal relationship should still be captured on the e-CRF:

• Interface intolerance due to excessive air leaks
• Pain
• Cutaneous pressure sore or pressure area
• Claustrophobia
• Oro-nasal dryness
• Respiratory acidosis with pH <7.25 prior to intubation
• Haemodynamic instability
• Vomiting
• Aspiration of gastric contents

Examples of other related events are pneumothorax and pneumomediastinum. Please note these events are now listed on the updated Data Collection CRF – v4.0 08 December 2020. Please use and file this version moving forward alongside the updated <u>master documents version log</u> – v9.0 21 Dec 2020.  

When assessing Serious Adverse Events, as per protocol section 4.1.4, events that commonly occur in this population and those that are collected as outcomes of the trial should NOT be reported as SAEs.

As a reminder this means the following events are EXEMPT from SAE reporting:

• Death
• Organ failure
•  Pneumonia
• Intubation
• Trachostomy

Events that are related to the patient’s underlying disease or condition should not be reported as this is not a relevant requirement for the trial.

“We just don’t know” Richard Innes, Consultant in Intensive Care at Somerset NHS Foundation Trust and Clinical Research Speciality Lead for Critical Care, says when describing the context for the RECOVERY-RS Study. The study looks to shed light on the most suitable form of ventilation to use when treating the patients worst affected by COVID-19.

Read more here: https://local.nihr.ac.uk/news/recovery-rs-addressing-clinical-equipoise-in-research/26414

Over 500 patients have now been recruited to the RECOVERY-RS trial! Thank you to everyone involved for all your hard work at sites and to patients & families for your generous participation.

A big thank you to everyone who joined the recent site teleconferences for RECOVERY-RS. We appreciate all of your feedback and hope you found these sessions useful & informative. Recruitment has been phenomenal these last few weeks and we have now reached a total of 509 patients recruited! Thank you to all involved.

Thanks again to Dr Messer & Dr Rostron for sharing their local experiences during the meeting of recruiting to RECOVERY-RS and how they have overcome challenges to embed the trial in to their clinical pathways. Thank you also to Dr Stephen Webb at Royal Papworth who provided really insightful comments yesterday regarding his altered view on CPAP. Experience during the second wave has shown concerns from ECMO centres about barotrauma from prolonged CPAP/NIV. This has led to a change in NHS guidance regarding ECMO criteria. Prolonged use of CPAP therefore may preclude option for ECMO leading to potential harm for CPAP. The only way to resolve these uncertainties is in a trial setting and through recruitment to RECOVERY-RS which will provide us with the evidence we need.

Summary minutes from the teleconferences will be circulated in the near future.

- Recording from TC held 24 Nov 20: https://files.warwick.ac.uk/eskilton/files/RECOVERY-RS+recordings/Site+TC+24Nov20+recording.mp4

- Slides from the TC meeting

- Local poster used at Heartlands (patient cards & poster) to assist with recruitment as a useful tool

- Trial certificate of appreciation to use to award trainees/staff involved in the study

- Slides from a recent TRIC & RAFT trainee meeting to share amongst trainee colleagues. Trainees can be critical to helping capture patients early on in their clinical pathway. A recording of Prof Gavin Perkins delivering these slides can be found here: https://files.warwick.ac.uk/eskilton/files/RECOVERY-RS+recordings/RECOVERY-RS+RAFT++TRIC+presentation+recording_23Nov20_.mp4

As a reminder all trial documentation including other aid memoirs can be downloaded from our trial website: https://warwick.ac.uk/fac/sci/med/research/ctu/trials/recovery-rs/sitestaff/ 

Thank you to everyone who was able to join our site teleconference yesterday. We really appreciated your feedback and we hope you found the session useful. Thank you to PI’s Dr Messer and Dr Rostron who provided valuable feedback on implementing the trial at their sites. Please see slides from the meeting and take note of the following important points:

CROSSOVER GUIDANCE

The following scenarios are exempt from crossover of trial intervention and going forward should not be reported on the e-CRF:

•Up to 6 hours of continuous use of crossover intervention

•Breaks for eating and drinking

•Bridge to intubation to stabilise the patient

•Palliative care purposes

Data collected up until this point may be queried in the new year with sites to reflect this guidance.

To note, expert consensus is to not use CPAP or HFNO for a second episode of non-invasive support. Should go straight to intubation.

TRAINEE COLLABORATION

A slide set and recording of Chief Investigator Gavin Perkins delivering this presentation aimed at TRIC & RAFT trainee networks is now available (please request recording from the trial team via email). We encourage you to circulate this amongst your trainees to encourage collaboration and to garner their support to help identify eligible patients. Capturing patients early on (e.g. ED, A&E) in their clinical pathway can be critical for success in the trial which trainees can assist with. To award trainee’s or anyone at your site working on the trial please feel free to use the certificate of appreciation template. If you have any further suggestions please let us know.

NEXT MEETING
The next session is taking place Wednesday 2 December 09:00 – 10:00 via Teams (please contact the trial team for joining information).

Recordings & minutes from the meeting will be distributed after next week’s session for anyone who cannot join.

Thanks again for all your hard work and efforts with recruitment which has been phenomenal over the last couple of months. We are now one of the largest non-invasive respiratory trials in the world which reflects the commitment and support for the trial.