Awake prone positioning in patients with hypoxemic respiratory failure due to COVID-19: the PROFLO multicenter randomized clinical trial

Abstract

Background The effect of awake prone positioning on intubation rates is not established. The aim of this trial was to investigate if a protocol for awake prone positioning reduces the rate of endotracheal intubation compared with standard care among patients with moderate to severe hypoxemic respiratory failure due to COVID-19. Methods We conducted a multicenter randomized clinical trial. Adult patients with confirmed COVID-19, high-flow nasal oxygen or noninvasive ventilation for respiratory support and a PaO2/FiO2 ratio ≤ 20 kPa were randomly assigned to a protocol targeting 16 h prone positioning per day or standard care. The primary endpoint was intubation within 30 days. Secondary endpoints included duration of awake prone positioning, 30-day mortality, ventilator-free days, hospital and intensive care unit length of stay, use of noninvasive ventilation, organ support and adverse events. The trial was terminated early due to futility. Results Of 141 patients assessed for eligibility, 75 were randomized of whom 39 were allocated to the control group and 36 to the prone group. Within 30 days after enrollment, 13 patients (33%) were intubated in the control group versus 12 patients (33%) in the prone group (HR 1.01 (95% CI 0.46–2.21), P = 0.99). Median prone duration was 3.4 h [IQR 1.8–8.4] in the control group compared with 9.0 h per day [IQR 4.4–10.6] in the prone group (P = 0.014). Nine patients (23%) in the control group had pressure sores compared with two patients (6%) in the prone group (difference − 18% (95% CI − 2 to − 33%); P = 0.032). There were no other differences in secondary outcomes between groups. Conclusions The implemented protocol for awake prone positioning increased duration of prone positioning, but did not reduce the rate of intubation in patients with hypoxemic respiratory failure due to COVID-19 compared to standard care. Trial registration ISRCTN54917435. Registered 15 June 2020 (https://doi.org/10.1186/ISRCTN54917435).

Find the real responders and improve the outcome of awake prone positioning

“…Second, Rosen and colleagues [ 1 ] reported a 33% intubation rate in both groups, which is much lower than that reported in two other studies [ 2 , 3 ] with similar baseline characteristics, degree of respiratory failure but shorter APP duration (41% and 49% in the control group and 40% and 58% in the prone group) compared with their investigation. Based on this data, could we speculate that prolonged APP does decrease the intubation rate?…”

“…We read with great interest of the report by Rosen and colleagues [ 1 ] about the effect of awake prone positioning (APP) on intubation rate among patients with moderate to severe hypoxemic respiratory failure (HRF) due to COVID-19. They identified a implemented protocol for APP increased duration of prone positioning, but did not reduce the rate of intubation compared to standard care.…”

“…First, in Rosen’s study [ 1 ], the patient in standard care group also received a median prone duration of 3.4 h compared with 9.0 h per day in the prone group, which means that the real intervention factor they investigated was whether a prolonged APP could further decrease intubation rate. Therefore, it may be more appropriate to draw a conclusion that prolonged APP did not reduce the rate of intubation in patients with HRF due to COVID-19.…”

“…Third, in Rosen’s study [ 1 ], most patients were put on APP when they were supported with noninvasive ventilation, which is a higher level support than high flow nasal canula (HFNC) [ 4 ]. This may indicate that they use the APP more like a “rescue” therapy rather than an “adjunctive” therapy in a late stage of ARF, which may get less response to APP and therefore less difference in intubation rate.…”

Letter to the Editor in response to “Find the real responders and improve the outcome of awake prone positioning”

“…We read with interest the letter by Wang and He [ 1 ] regarding our trial of awake prone positioning (APP) in severe COVID-19 [ 2 ] and would like to discuss the questions they raised.…”