NCT05056090: PROMILD

Effect of Prone Positioning on Mortality in Patients With Mild to Moderate Acute Respiratory Distress Syndrome.

Status unknown NA Last updated 7 November 2022

What this trial tests

NA trial testing Patients will receive MV in PP in ARDS in 656 participants. Status unknown.

Timeline

1 September 2021

Primary endpoint
28 September 2023

1 March 2024

Quick facts

Lead sponsor	University Hospital, Grenoble
Phase	NA
Status	Status unknown
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	656
Start date	1 September 2021
Primary completion	28 September 2023
Estimated completion	1 March 2024
Sites	1 location across France

Drugs / interventions tested

• Patients will receive MV in PP

Conditions studied

• ARDS — all drugs for ARDS →
• Acute Respiratory Distress Syndrome — all drugs for Acute Respiratory Distress Syndrome →
• Intensive Care Unit — all drugs for Intensive Care Unit →
• Mechanical Ventilation — all drugs for Mechanical Ventilation →

Sponsor

University Hospital, Grenoble

Who can join

18 and older, any sex, with ARDS or Acute Respiratory Distress Syndrome. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Acute respiratory distress syndrome (ARDS) accounts for almost 10% of intensive care units (ICU) admissions. Three ARDS stages have been defined, based on the PaO2/FIO2 ratio measured with positive end-expiratory pressure (PEEP) ≥5 cmH2O: mild (201-300 mmHg), moderate (200-101 mmHg), and severe (≤100mmHg). They represent 30.0%, 46.6%, and 23.4% of ARDS, respectively.

Mechanical invasive ventilation (MV), the cornerstone of ARDS patient care, has a primary goal to protect the lung from ventilator-induced lung injury (VILI). Delivering MV in a prone position (PP) has been shown to improve oxygenation, protect the lung through a better homogenization of lung stress/strain, and stabilize hemodynamics.

A meta-analysis of four randomized controlled trials showed beneficial effect of PP vs. supine position (SP) in the most hypoxemic patients. A fifth randomized controlled trial further showed a significant reduction in mortality with PP in ARDS patients with PaO2/FIO2 \<150 mmHg, when neuromuscular blockade and long prone positioning sessions were used. Therefore, PP has since been strongly recommended for ARDS patients with PaO2/FIO2 \<150 mmHg. Yet, there is limited evidence in patients with mild to moderate ARDS.

There are, however, strong arguments supporting the need for a new trial in ARDS patients with PaO2/FIO2 in the range 150-300 mmHg:

1. There is no trial that has specifically tested PP in this ARDS subset;
2. PP is safe and has become a standard of care in ICU;
3. Should VILI prevention be a mechanism through which PP improves survival, this should be involved in all ARDS patients;
4. The mortality at hospital discharge in this subset of ARDS remains significant, amounting to 34.9% (95% confidence intervals 31.4-38.5%) in mild and 40.3% (37.4-43.3) in moderate stages;
5. Among 580 patients with mild ARDS at admission to the ICU, in-hospital mortality was 10%, 30%, and 37% for those who improved, persisted, and worsened ARDS, respectively.
6. Finally, PP has been shown to be cost-effective under commonly accepted thresholds.

The hypothesis is that in patients within the 150-300mmHg PaO2/FIO2 range at the time of ARDS diagnosis, PP can reduce mortality as compared to a similar group left in the SP.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. ESICM guidelines on acute respiratory distress syndrome: definition, phenotyping and respiratory support strategies.
   Grasselli G, Calfee CS, Camporota L, Poole D, et al · · 2023 · cited 606× · PMID 37326646 · DOI 10.1007/s00134-023-07050-7