Covid-19 Living Data

Trial ISRCTN54918435
Publication Rosen J, Crit Care, 2021 (published paper)
Dates: 2020-10-07 to 2021-02-07
Funding: Public/non profit (Uppsala University; Regional councils of Uppsala, Stockholm and Jönköping; Swedish Heart–Lung Foundation)
Conflict of interest: Yes

Methods
	RCT Blinding: Unblinded
	Location : Multicenter / Sweden Follow-up duration (days): 30
Inclusion criteria	- Adults (≥ 18 years old) - with COVID-19 verified by positive SARS-CoV-2 reverse transcription polymerase chain reaction tests on naso- or oropharyngeal swabs - hypoxemic respiratory failure requiring HFNO or NIV - PaO2/FiO2-ratio ≤ 20 kPa or corresponding values of SpO2 and FiO2 (FiO2:0.40 and SpO2: ≤ 90%, FiO2:0.45 and SpO2: ≤ 92%, FiO2:0.50 and SpO2: ≤ 94%, FiO2:0.55 and SpO2: ≤ 96%, FiO2:0.60 and SpO2: ≤ 98%) for more than one hour
Exclusion criteria	- oxygen supplementation with a device other than HFNO or NIV; - inability to assume prone or semi-prone position; - immediate need for endotracheal intubation; - severe hemodynamic instability; - previous intubation for COVID-19 pneumonia; - pregnancy; - terminal illness with less than one year life expectancy; - do-not-intubate order; - inability to understand oral or written study information
Interventions
	Treatment Prone position At least 16 h APP per day. Prone and semi-prone positioning were allowed
	Control Standard care ( / ) Definition of Standard care: According to clinical practice in participating hospitals. Intravenous sedation was allowed but not protocolized. Decision to intubate was made at the discretion of the attending clinician but followed local guidelines. Positioning after intubation was not protocolized, but liberal prone positioning was part of the clinical routine for mechanically ventilated patients with COVID-19 fulfilling criteria for moderate to severe ARDS at all three centers.
Participants
	Randomized 75 participants (n₁=36 / n₂= 39)
	Characteristics of participants N=75 Mean age : NR 55 males Severity : Mild: n=0 / Moderate: n=0/ Severe: n=75 Critical: n=0
Primary outcome
	In the register Rate of intubation for mechanical ventilation support, recorded in EHR at inclusion and once if applied. Timeframe 30 days after inclusion.
	In the report Intubation within 30 days after enrollment
Documents available	Protocol Yes. In English Statistical plan NR Data-sharing stated
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Some concerns
General comment	In addition to the published report, the pre-print article, the study registry, protocol and statistical analysis plan were used in data extraction and risk of bias assessment. The study did not achieve the target sample size specified in the trial registry. The trial was terminated for futility. Quote: "Due to rapidly declining case numbers, the interim analysis was performed when 75 patients had been included in the study. Based on this analysis, the data and safety monitoring board recommended to stop the trial due to futility." There is no change from the trial registration in the intervention and control treatments. The registry's primary outcome reflects the reported primary outcome. Some outcomes from the registry are not reported in the paper (e.g. 7-day mortality, days on ventilator support). Some outcomes (e.g. days free from ventilator support) are reported in the paper, but were not pre-specified in the trial registry/protocol. Time to death was not pre-specified, but could be extracted from the effect estimate from the mortality outcome (i.e. Hazard ratio) and was therefore not considered to be selected from multiple outcome measurements. It is unclear what type of funding was gained for this trial (the registry states 'private' yet only reports on one funding source compared to that listed in the pre-print and published report). This study was updated on July 8th, 2021 with data from the published report.