NCT04607551: PRONECMO

PRONing to Facilitate Weaning From ECMO in Patients With Refractory Acute Respiratory Distress Syndrome

Completed NA Last updated 1 March 2023

What this trial tests

NA trial testing Prone positionning in ARDS in 170 participants. Completed in 31 December 2022.

Timeline

3 March 2021

Primary endpoint
7 March 2022

31 December 2022

Quick facts

Lead sponsor	Assistance Publique - Hôpitaux de Paris
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	other
Enrollment	170
Start date	3 March 2021
Primary completion	7 March 2022
Estimated completion	31 December 2022
Sites	1 location across France

Drugs / interventions tested

• Prone positionning
• Supine position

Conditions studied

• ARDS — all drugs for ARDS →

Sponsor

Assistance Publique - Hôpitaux de Paris — full company profile →

Who can join

Adults 18 to 75, any sex, with ARDS. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

ECMO has emerged as a promising intervention that may provide more efficacious supportive care to patients with refractory severe acute respiratory distress syndrome (ARDS). The largest randomized trial of ECMO for severe forms of ARDS was recently published and demonstrated no significant benefit from early initiation of ECMO with respect to 60-day mortality, when compared with a strategy of conventional mechanical ventilation (MV) (ref EOLIA). However, a rescue ECMO option was used by 28% of the controls, which is likely to have diluted the potential positive effect of ECMO. One may argue that a less restrictive primary endpoint, such as death or rescue ECMO, would have yielded positive findings.

Meanwhile, improvements in technology have made ECMO safer and easier to use, allowing for the potential of more widespread application in patients with ARDS. VV-ECMO can be used as a life-saving rescue therapy in patients with ARDS when MV cannot maintain adequate oxygenation or CO2 elimination. Alternatively, VV-ECMO may be used in patients who remain hypoxemic during MV (i.e., PaO2/FiO2\<80 mmHg) despite optimization of MV (including the application of high levels of positive end-expiratory pressure (PEEP), neuromuscular blockers, and prone positioning) and allow "lung rest" by lowering airway pressures and tidal volume to ameliorate ventilator-induced lung injury (VILI).

Prone positioning (PP) has been used for more than 30 years in patients with acute hypoxemic respiratory failure and in particular with ARDS. Initially, PP in ARDS patients was proposed as an efficient mean to improve oxygenation, sometimes dramatically, in a large number of patients. In addition, it is now clear, and data are still accumulating, that PP is also able to prevent VILI which is as important as maintaining safe gas exchange in mechanical ventilation. Therefore, PP is a strategy that covers the two major goals of ventilator support in ARDS patients, maintaining safe oxygenation and preventing VILI and reducing mortality at the end. This latter objective makes sense on ECMO as one of the main objective of this device is to markedly reduce VILI by resting the lung.

Considering that PP is a valuable and safe therapy to reduce VILI, its combination with ECMO could enhance VILI prevention. In recent preliminary studies, it was reported that the combination of VV-ECMO and PP was associated with a dramatic improvement in oxygenation, in pulmonary and thoracic compliance and in chest X-ray findings. It may thus facilitate the weaning of ECMO and can be performed without compromising the safety of the patients. Lung recruitment and improvement in ventilation/perfusion mismatch on prone position may both contribute to improve oxygenation. PP may therefore be efficient to hasten the weaning of VV-ECMO when atelectasis and ventilation/perfusion mismatch occur under ultra-protective ventilation even in patients in whom pre-ECMO PP failed. In addition, it could also enhance ventilator induced lung injury prevention on ECMO.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Prone position for acute respiratory failure in adults.
   Bloomfield R, Noble DW, Sudlow A. · · 2015 · cited 93× · PMID 26561745 · DOI 10.1002/14651858.cd008095.pub2
2. Prone Positioning During Extracorporeal Membrane Oxygenation in Patients With Severe ARDS: The PRONECMO Randomized Clinical Trial.
   Schmidt M, Hajage D, Lebreton G, Dres M, et al · · 2023 · cited 60× · PMID 38038395 · DOI 10.1001/jama.2023.24491
3. Effect of prone positioning on survival in adult patients receiving venovenous extracorporeal membrane oxygenation for acute respiratory distress syndrome: a systematic review and meta-analysis.
   Papazian L, Schmidt M, Hajage D, Combes A, et al · · 2022 · cited 54× · PMID 35037993 · DOI 10.1007/s00134-021-06604-x
4. Prone positioning during venovenous extracorporeal membrane oxygenation for acute respiratory distress syndrome: a systematic review and meta-analysis.
   Poon WH, Ramanathan K, Ling RR, Yang IX, et al · · 2021 · cited 44× · PMID 34384475 · DOI 10.1186/s13054-021-03723-1
5. Prone positioning during venovenous extracorporeal membrane oxygenation for acute respiratory distress syndrome: a pooled individual patient data analysis.
   Giani M, Rezoagli E, Guervilly C, Rilinger J, et al · · 2022 · cited 41× · PMID 34986895 · DOI 10.1186/s13054-021-03879-w
6. Setting and Monitoring of Mechanical Ventilation During Venovenous ECMO.
   Assouline B, Combes A, Schmidt M. · · 2023 · cited 23× · PMID 36941722 · DOI 10.1186/s13054-023-04372-2
7. Effects of Prone Positioning on Respiratory Mechanics and Oxygenation in Critically Ill Patients With COVID-19 Requiring Venovenous Extracorporeal Membrane Oxygenation.
   Laghlam D, Charpentier J, Hamou ZA, Nguyen LS, et al · · 2021 · cited 11× · PMID 35111786 · DOI 10.3389/fmed.2021.810393
8. Extracorporeal Gas Exchange for Acute Respiratory Distress Syndrome: Open Questions, Controversies and Future Directions.
   Giani M, Giani M, Redaelli S, Siragusa A, et al · · 2021 · cited 10× · PMID 33670987 · DOI 10.3390/membranes11030172