Recent version control monitoring checks have revealed some discrepancies with the wrong versions of Patient Information Sheets and Consent forms used as sites have found the naming of documents confusing to navigate. We apologise for the confusion caused and to help provide clarity of which version to use please see the following table:

As a reminder, if you are unable to obtain consent from a patient with mental capacity or consultee post randomisation before they are discharged/transferred from hospital, you should attempt to contact the patient/consultee up to 3 times by telephone to seek verbal agreement. If you are unsuccessful in reaching them after 3 attempts you do not need to contact them further as we have permission from our REC for the patient’s data to remain in the trial.

RECOVERY-RS is now the largest global non-invasive respiratory support trial for COVID-19 with 1,106 patients recruited as of this morning. We would like to say a huge thank you to all the staff, patients and families involved for helping us reach this incredible milestone!

The DMC for RECOVERY-RS met at the end of January. They noted the considerable progress that had been made since the last DMC meeting, with over 1000 participants now enrolled, making the trial the world’s largest trial of non-invasive ventilation in acute respiratory failure. After careful consideration of the available data, the committee recommended that recruitment continues. A further review will be considered in 4 weeks time. The committee requested that we prioritise obtaining the outcome data for those enrolled to date. We plan to work with NHS Digital, ICNARC and our recruiting sites to obtain as much information as possible to inform the next review.

The investigator team would like to extend their sincere thanks to the patients, families, clinicians and research teams who have supported the trial to date. We plan to provide a further update following the next interim analysis.

RECOVERY-RS team.

A big thank you to all of our recruitment sites, patients and families for helping us reach the milestone of 900 patients recruited. Recruitment has been phenomenal the last few weeks and your hard work does not go unnoticed. Thank you!

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.