Clinical trial NCT04589936: Prone Position to Improve Oxygenation in COVID-19 Patients Outside Critical Care
Official title: Prone Position to Improve Oxygenation in COVID-19 Patients Outside Critical Care (PRONE-COVID Study)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Pneumonia
Covid19
Keywords: Prone positioning
COVID-19
Pneumonia
Oxygenation
Lead sponsor: Cambridge University Hospitals NHS Foundation Trust
Sponsor class: OTHER
First posted: 2020-10-19
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Case-control study design, with 1:1 for COVID-19 case versus pneumonia unrelated to COVID-19.
Primary purpose: TREATMENT

Brief summary: Prone positioning is known to improve the PaO2/FiO2 ratio and reduce mortality in patients with ARDS managed in the critical care setting. Therefore, it is incorporated into regular clinical practice of managing patients with ARDS in critical care and is being used as such in the COVID-19 outbreak. Given that prone positioning is recommended by the Intensive Care Society in non-ventilated patients with COVID-19, there is an urgent need to better understand the physiological effects of prone positioning in such cases. Furthermore, the translation and applicability of such a low-cost non-invasive intervention in a wider group of patients with pneumonia not specific to covid-19 infection, is an important consideration that merits investigation.

This single-centred observational study conducted at Cambridge University Hospitals NHS Foundation Trust aims to improve understanding of physiological effects of prone positioning in non-ventilated patients with COVID-19 and a control group of patients with non-COVID-19 related pneumonia. The study also aims to incorporate a small subset of patients, with an approximately even spread of COVID-19 and non-COVID cases, which allows for an additional exploratory descriptive report on prone positioning over a 24-hour period.

This study proposes that prone positioning improves oxygenation in non-ventilated patients with pneumonia (COVID-19 related or not) requiring supplemental oxygen managed outside of the critical care setting.

Detailed description: COVID-19 (coronavirus disease 2019) caused by the infectious agent, SARS-CoV-2, was first recognised in Wuhan, Hubei Province, China in December 2019. Whilst a large proportion of COVID-19 illness within the community is mild, patients who are admitted to hospital with COVID-19 often have more severe disease and have a higher risk of developing COVID-19 complications including ARDS. Patients with ARDS are often managed on intensive care units that have evidence-based protocols for managing patients with ARDS. Prone positioning for such patients is a well-recognised component of ARDS critical care management. It is known to improve oxygenation and reduce oxygen requirements, as well as reduce mortality in patients with moderate to severe ARDS managed in critical care. The benefits of prone positioning as a technique to improve oxygenation in awake, non-intubated patients is less well-established. A few studies have showed prone positioning to be well-tolerated and improved oxygenation amongst non-intubated patients without respiratory support, as well as those requiring high-flow nasal oxygen or non-invasive ventilation support.

It remains unknown whether prone positioning is beneficial in patients with COVID-19 earlier in their disease, prior to requirement of non-invasive or invasive ventilation. This study therefore aims to better understand the physiological effects of prone positioning in patients with pneumonia with and without COVID-19.

This will be a single-centred interventional case-control study, comparing physiological effect of prone positioning in COVID-19 cases versus pneumonia unrelated to COVID-19. A sub-study of a smaller number of enrolled patients, with approximately even spread of COVID-19 and non-COVID cases, will allow an additional exploratory descriptive report on prone positioning over a 24-hour period.

Participant will be fitted with a Masimo monitoring device that enables continuous monitoring, and subsequent data storage and download of SpO2, heart rate, end tidal CO2 and respiratory rate. The sub-study investigating the effects of a longer duration of proning will involve applying a non-invasive positional sensor to automatically detect the participant's position, and correlate it with the patient's physiological parameters as well as tolerability. Qualitative data on patient's tolerability of prone positioning will also be collected.

It is anticipated that each participant will be their own control, enabling comparison of SpO2 in supine, lateral, prone and again supine positions. Summary statistics of mean, median, range, interquartile range, and range for each position for participants will be summarised. The data from the two arms will initially be analysed separately, then pooled to determine if a larger sample size impacts results. A multilevel regression model with average SpO2 as outcome will be fitted to assess the effect of lying position on SpO2. Additional models such as mixed models incorporating multiple repeated measurements/endpoints may be considered/fitted for exploratory analyses. Data from questionnaires will be reported by summary statistics where possible. Free text responses may be grouped into themes, and parametric or non-parametric tests will be used to analyse the VAS data further.

All data will be transferred into a Case Report Form (CRF) which will be anonymised. The investigator will obtain written informed consent from each participant before any study-specific activity is performed. Before the start of the study, or implementation of any amendment, we will obtain approval of the protocol, protocol amendments, informed consent forms and other relevant documents from the REC.

Eligibility criteria: Inclusion Criteria:

1. Have confirmed or suspected COVID-19 or non-COVID pneumonia (confirmed with radiological changes)
2. FiO2 ≥24% or requiring basic respiratory support (supplementary oxygen via face mask, nasal cannula, venturi, non-rebreathe bag) to achieve clinical target SpO2 (e.g. SpO2 92-96%), ensuring patient is on appropriately titrated oxygen to be within this range.
3. Be able to provide informed consent
4. Communicate and cooperate with the procedure
5. Rotate and adjust position independently
6. No anticipated airway issues

Exclusion Criteria:

The presence of any of the following will mean participants are ineligible:

1. Signs of respiratory distress (e.g. respiratory rate ≥35, accessory muscle use)
2. Immediate need for intubation
3. Haemodynamic instability or new arrhythmia
4. Unstable spine/thoracic injury/recent abdominal surgery
5. Pregnancy (2nd/3rd trimester)
6. At risk of pressure sores/ulcers
7. Neurological issues-frequent seizures
8. Facial injury that would make prone position difficult
9. Gastrointestinal issues-frequent vomiting or diarrhoea that would make prone position difficult

Primary outcomes:
measure: Peripheral Oxygen saturation
timeFrame: 1 year (June 2021)
Secondary outcomes:
measure: PaO2 :FiO2 ratio calculated from formulae
timeFrame: 1 year (June 2021)
measure: Respiratory rate measured with Masimo device
timeFrame: 1 year (June 2021)
measure: Heart rate measured with Masimo device
timeFrame: 1 year (June 2021)
measure: Blood pressure measured with Masimo device
timeFrame: 1 year (June 2021)
measure: Patient reported severity of breathlessness on a continuous linear scale of 0 to 10cm (10cm being the most severe)
timeFrame: 1 year (June 2021)
measure: Patient tolerability of prone position on a continuous linear scale of 0 to 10cm (10cm being the most unacceptable)
timeFrame: 1 year (June 2021)
measure: Investigator experience of delivering prone positioning
timeFrame: 1 year (June 2021)
measure: To assess patient's peripheral oxygen saturation
timeFrame: 1 year (June 2021)
Other outcomes:
Locations:
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust
state: Cambridgeshire
Study officials:
affiliation: Cambridge University Hospitals NHS Foundation Trust
name: Jonathan Fuld
role: PRINCIPAL_INVESTIGATOR
References:
citation: Elharrar X, Trigui Y, Dols AM, Touchon F, Martinez S, Prud'homme E, Papazian L. Use of Prone Positioning in Nonintubated Patients With COVID-19 and Hypoxemic Acute Respiratory Failure. JAMA. 2020 Jun 9;323(22):2336-2338. doi: 10.1001/jama.2020.8255.