Awake Prone Positioning in Moderate to Severe COVID-19

The purpose of this study is comparing vital signs between standard care and prone position groups. Standard care will consist of routine clinical care, including any advice to lie in prone position as routinely recommended by participating sites. For those randomized to prone position, a special intervention team will visit patients' rooms aiming for patients to maintain the prone position for at least 8 hours a day.

This study is a pragmatic open label randomised controlled trial. After being informed about the study and potential risks, all patients having written informed consents will be randomised into two groups. Standard care group will consist of routine clinical care, including any advice to lie in prone position as routinely recommended by participating sites. To reduce bias, the study team will make visits at a similar schedule to those to patients in the intervention group, however these visits will be confined to general advice and measurement of vital signs. Patients will receive written advice more general in nature about COVID-19 disease. For those randomized to prone position group, a special intervention team will visit patients' rooms aiming for patients to maintain the prone position for at least 8 hours a day. The team will give written and verbal advice and if necessary aid patients' positioning themselves in the prone position. The exact duration of prone sessions will be determined according to ward schedules to take account of nursing procedures, meal times and mitigation strategies. Other methods to encourage the maintenance of prone position includes phone calls to patients, carers or education of carers. Compliance with the intervention will be evaluated by observation (manual and using in-room cameras) at fixed time intervals. In a subgroup of 100 patients accelerometer/gyrometer devices will be used to measure movement and position (this will be expanded to all patients if equipment is available). Other outcome measures (SpO2, heart rate etc) will be measured using standard monitoring equipment currently used at study sites, including wearable devices.

COVID-19, SARS-CoV2 Infection, COVID-19 Acute Respiratory Distress Syndrome, Acute Hypoxemic Respiratory Failure, Respiratory Distress Syndrome, Adult

Standard care will consist of routine clinical care, including any advice to lie in prone position as routinely recommended by participating sites

prone position group will have a special intervention team who visits patients' rooms aiming for patients to maintain the prone position for at least 8 hours a day

The team will give written and verbal advice and if necessary aid patients' positioning themselves in the prone position for at least 8 hours per day. The exact duration of prone sessions will be determined according to ward schedules to take account of nursing procedures, meal times and mitigation strategies. Other methods to encourage the maintenance of prone position includes phone calls to patients, carers or education of carers.

Escalation of respiratory therapy within 28 days of randomization, defined as any of the following: Escalation to next level respiratory support (with lowest level nasal cannula or face mask, escalating through HFNC to NIV or mechanical ventilation). Intubation

SpO2, respiratory rate, heart rate, FiO2, ROX index will be documented before and at end of period of prone positioning every day. The improvement will be measured by resolution of them compared with baseline parameters

An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the medical treatment or procedure that may or may not be considered related to the medical treatment or procedure. The severity of all AEs in this trial should be graded in line with the toxicity grading in Toxicity grading and management (CTCAE)

Inclusion Criteria: Probable or confirmed COVID-19 infection according to WHO criteria Moderate or severe COVID-19 respiratory infection according to Vietnamese guidelines Requirement for supplemental oxygen therapy Exclusion Criteria: Invasive mechanical ventilation, or non-invasive ventilation (NIV) with CPAP or BiPAP or imminent need for these Contraindications to prone position (see Appendix 5) Pregnancy Severe obesity (BMI >35), Altered level of consciousness (GCS <13) Attending doctor judged prone position to be unsuitable for the patient for any reason Patients in whom there is a decision that care will not be escalated Failure to have informed consent

Anonymised data of this study may be requested for publication by journals. Sharing anonymised data with future similar/suitable studies will be decided by the sponsor, PIs and the authority agency where the data was collected. No identifiable information will be shared with any other person/organisation

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