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Trial registered on ANZCTR


Registration number
ACTRN12620000740998
Ethics application status
Approved
Date submitted
27/04/2020
Date registered
16/07/2020
Date last updated
16/07/2020
Date data sharing statement initially provided
16/07/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
A Study of Lying Face Down to Help Improve Oxygen Levels of Adults Not Needing Ventilators in Intensive Care with COVID-19
Scientific title
A Randomised Controlled Trial of Early Prone Positioning to Improve Oxygenation in Non-Intubated Adults Admitted to Intensive Care with COVID-19
Secondary ID [1] 301099 0
None
Universal Trial Number (UTN)
Trial acronym
ROLL OVER COVID Trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
COVID-19 317237 0
SARS-CoV-2 317238 0
Condition category
Condition code
Respiratory 315373 315373 0 0
Other respiratory disorders / diseases
Infection 315419 315419 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients enrolled in the intervention arm will be asked to lie prone according to an "intervention plan". In short, they will be enrolled with the aim of lying prone for up to 12 hours a day in a prone position. This time does not have to be continuous and it will be suggested that it is broken into smaller time periods, tailored to each patients level of comfort.

There is no minimum time been period of pruning and no restriction on participants positioning outside of the 'intervention' periods.

If this duration is not tolerated for an individual patient, staff will trial a variety of comfort measures - for example, adding pillow padding under thighs and shoulders, adjusting each patients prone position modified swimmers position and then if required follow a planned ‘de-escalation’ protocol, to find the maximum tolerable proning time for each patient.
The intervention will continue for 72 hours (a maximum of 36 hours prone).

If a participant is unable to tolerate a 12h/day prone position as above, this can be reduced. A comfortable ‘proning limit’ for each patient can be found and then this can continue for the remaining trial period.
Step 1 - Trial 3 x 3hr sessions/9 hours a day
Step 2 - If needing longer breaks not prone - Trial 2 x 4hr sessions/8 hours a day
Step 3 - Trial 2 x 3hr sessions/6 hours a day
Step 4 - 3 x 2 hour sessions/6 hours a day
Step 5 - 2 x 2 hours sessions/4 hours a day
Step 6 - Abandon proning, document in EMR why proning was abandoned
Intervention code [1] 317437 0
Treatment: Other
Comparator / control treatment
The control groups will receive standard care in our intensive care unit.

It is anticipated most patients will lie i bed supine overnight, perhaps in left or right lateral positions, and then will be sitting upright during periods of the day, possibly out of bed. There will be no restriction on the patients movements or positions in the control group.
Control group
Active

Outcomes
Primary outcome [1] 323619 0
Oxygen Saturations in the blood will be compared

By assessing the difference in average gradient of the PaO2:FiO2 (PF ratio) in the prone and control groups over the trial period (72 hours). Calculate by pulse oximetry recordings and oxygen delivery method as recorded in the medical chart, calculated by methods describe in the literature, utilising the equation log(P:F Ratio) = 0.48+0.78log(S:F Ratio).
Timepoint [1] 323619 0
During study period (Study Days 1-3 inclusive) in the intervention group
Secondary outcome [1] 382388 0
Median number of hours spent prone per day during trial period in the intervention group, as recorded in the medical chart by the treating nurse
Timepoint [1] 382388 0
During study period (Study Days 1-3 inclusive) in the intervention group
Secondary outcome [2] 382389 0
Number of adverse events in the prone group compared to control, as collected by staff survey, and any other incidence of adverse events brought to the attention of investigators.

For example we are collection information on the incidence of:
Dislodgement of supplemental oxygen delivery device
Dislodgement of Venous Access
Dislodgement of Arterial Access
Dislodgement of Another Catheter (IDC, Chest tube etc.)
New Pressure Area (not present/recorded at start of trial) (Stage of Pressure Area – as per the National Pressure Ulcer Advisory Panel (NPUAP) 2016 Pressure Injury Staging Illustrations)
Facial Oedema
Required sedation for agitation
Hypotension on repositioning
Desaturation - not requiring a change in management
Desaturation - requiring a change in management e.g. increased FiO2
Vomiting
Arrhythmias
Cardiac Arrest
Other (Free text)
Timepoint [2] 382389 0
During study period (Study Days 1-3 inclusive) in the intervention group

Eligibility
Key inclusion criteria
*Adults, over the age of 18
*COVID-19 Diagnosis Confirmed – either by PCR or as per any unit policy changes that may be applied during the enrolment period
*Admitted to Intensive Care
*Any severity of disease (As defined by National COVID 19 Clinical Evidence Taskforce "Australian Guidelines for the clinical care of people with COVID-19" assessable at https://covid19evidence.net.au ). For patients with severe disease, the treating intensivist must be consulted prior to randomisation (see exclusion criterion #2)
*Willing and able to tolerate prone positioning (A pre-enrollment screening test to ensure they can tolerate the position and can maneuver into & out of the prone position with minimal assistance from their usual care staff only. )
*Prior informed consent has been obtained from the patient
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Intubated, or expected to be intubated in the next 12 hours
* Non Intubated patients with severe disease where the treating intensivist (or an intensivist who is not a study investigator) has any safety concerns regarding the use of prone positioning
*Previously intubated for COVID-19, or in the recovery phase of their illness.
*Current (or expected) treatment limits such as ‘not for CPR’ or end-of-life care orders
*If in the judgment of the treating clinical team there is any other medical condition present which may reduce the safety of the prone positioning. Examples would include pregnancy, concurrent spinal precautions, severe cervical spine arthritis.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation concealment & randomisation will occur via sequentially numbered opaque sealed envelopes (SNOSE) in a technique described elsewhere. (Doig GS, Simpson F. Randomization and allocation concealment: a practical guide for researchers. J Crit Care. 2005;20(2):187-91; discussion 91-3.)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be blocked by random permuted blocks to ensure equal allocation, and stratified by single factor, presence of severe disease as defined in the nation consensus guidelines
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 16576 0
Royal Prince Alfred Hospital - Camperdown
Recruitment postcode(s) [1] 30137 0
2050 - Camperdown

Funding & Sponsors
Funding source category [1] 305569 0
Hospital
Name [1] 305569 0
Royal Prince Alfred Hospital
Address [1] 305569 0
Missenden Road
Camperdown
NSW 2050
Country [1] 305569 0
Australia
Primary sponsor type
Hospital
Name
Royal Prince Alfred Hospital
Address
Missenden Road
Camperdown
NSW 2050
Country
Australia
Secondary sponsor category [1] 305979 0
None
Name [1] 305979 0
Address [1] 305979 0
Country [1] 305979 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305847 0
Sydney Local Health District Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 305847 0
Royal Prince Alfred Hospital
Missenden Road
Camperdown
NSW 2050
Ethics committee country [1] 305847 0
Australia
Date submitted for ethics approval [1] 305847 0
22/04/2020
Approval date [1] 305847 0
18/06/2020
Ethics approval number [1] 305847 0

Summary
Brief summary
Prone positioning (lying face down) is a recognised rescue therapy for ventilated patients with severe lung disease whose oxygen levels remain low despite optimal ventilation strategies. We look to investigate whether proning early during admission to the Intensive Care Unit, might improve oxygenation for patient with COVID-19.
Objectives: To determine the efficacy and safety of early prone positioning, compared to usual care, on oxygenation for non intubated adults admitted to ICU with COVID-19.

Hypothesis: That the intervention (prone positioning) will improve measured oxygen levels in patients with COVID-19
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 101802 0
Dr Thomas Melhuish
Address 101802 0
Intensive Care Services
Royal Prince Alfred Hospital
Missenden Road
Camperdown
NSW 2050
Country 101802 0
Australia
Phone 101802 0
+61 02 9515 6111
Fax 101802 0
Email 101802 0
thomas.melhuish@health.nsw.gov.au
Contact person for public queries
Name 101803 0
Dr Thomas Melhuish
Address 101803 0
Intensive Care Services
Royal Prince Alfred Hospital
Missenden Road
Camperdown
NSW 2050
Country 101803 0
Australia
Phone 101803 0
+61 02 9515 6111
Fax 101803 0
Email 101803 0
thomas.melhuish@health.nsw.gov.au
Contact person for scientific queries
Name 101804 0
Dr Thomas Melhuish
Address 101804 0
Intensive Care Services
Royal Prince Alfred Hospital
Missenden Road
Camperdown
NSW 2050
Country 101804 0
Australia
Phone 101804 0
+61 02 9515 6111
Fax 101804 0
Email 101804 0
thomas.melhuish@health.nsw.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Our ethical approval application will not include the distribution of IPD.
What supporting documents are/will be available?
Study protocol
Statistical analysis plan
Informed consent form
Ethical approval
How or where can supporting documents be obtained?
Type [1] 7785 0
Study protocol
Citation [1] 7785 0
Link [1] 7785 0
Email [1] 7785 0
thomas.melhuish@health.nsw.gov.au
Other [1] 7785 0
Attachment [1] 7785 0
Type [2] 7786 0
Statistical analysis plan
Citation [2] 7786 0
Link [2] 7786 0
Email [2] 7786 0
thomas.melhuish@health.nsw.gov.au
Other [2] 7786 0
Attachment [2] 7786 0
Type [3] 7787 0
Informed consent form
Citation [3] 7787 0
Link [3] 7787 0
Email [3] 7787 0
thomas.melhuish@health.nsw.gov.au
Other [3] 7787 0
Attachment [3] 7787 0
Type [4] 7788 0
Ethical approval
Citation [4] 7788 0
Link [4] 7788 0
Email [4] 7788 0
thomas.melhuish@health.nsw.gov.au
Other [4] 7788 0
Attachment [4] 7788 0
Summary results
No Results