Clinical trial NCT06854627: Effect of Continuous Prolonged Prone Position Versus Intermittent Daily Prone Position in ARDS
Official title: Effect of Continuous Prolonged Prone Position Versus Intermittent Daily Prone Position on Mortality in ARDS Patients: A Multicenter Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Acute Respiratory Distress Syndrome
Keywords: ACUTE RESPIRATORY DISTRESS SYNDROME
RESPIRATORY FAILURE
PRONE POSITION
MECHANICAL VENTILATION
Lead sponsor: Pontificia Universidad Catolica de Chile
Sponsor class: OTHER
Collaborators: name: Hospital do Coracao
name: Fundacion Clinica Valle del Lili
name: Fondo Nacional de Desarrollo Científico y Tecnológico, Chile
First posted: 2025-03-03
Enrollment: 780
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Study do not use Drug, Biological/Vaccine, or Combination Product.
Primary purpose: OTHER

Brief summary: Prone position (placing the patient on his abdomen) has been shown to be an effective intervention to decrease mortality in adults connected to mechanical ventilation for moderate to severe Acute Respiratory Distress Syndrome (ARDS). Patients may require one or more sessions of prone position. However, the optimal duration of prone sessions is unknown. The goal of this clinical trial is to learn if applying prone position in prolonged sessions (\> 48 hours - prolonged prone position) is more effective than applying it in daily sessions (16 to 24 hours - intermittent prone position). The trial will also learn about the safety of prolonged prone position compared to intermittent prone position. The main questions it aims to answer are:

* Does prolonged prone position increase survival compared to intermittent prone position in participants with moderate to severe ARDS ?
* How does prolonged prone position compare to intermittent prone position in terms of medical problems associated to prone position ?

Researchers will compare prolonged versus intermittent prone position to see which approach is better to treat moderate to severe ARDS.

Participants will:

* Receive prone position either in prolonged (\> 48 hours) or daily (16 to 24 hours) sessions during the first 7 days
* Be followed for up to 90 days to assess their clinical evolution

Detailed description: Acute Respiratory Distress Syndrome (ARDS) is a severe condition with a 40% mortality rate. The management of ARDS still relies largely on supportive therapy. The cornerstone of this support is protective mechanical ventilation to prevent ventilator-induced lung injury (VILI). For patients with moderate-to- severe forms of ARDS, specifically mechanically ventilated patients with PaO2/FiO2 ratios below 150, the use of prone position has shown to be a fundamental intervention which became one of the most relevant pillars of the ICU management during the Covid-19 pandemics. Several studies have shown that prone position not only improves oxygenation, but can attenuate the mechanisms of VILI, which would explain its benefit in terms of mortality. The physiologic benefits of prone position are progressive along time, but they can be lost rapidly after returning to supìne position.

Since the publication of the landmark PROSEVA study (Guerin 2013), which showed that ventilating patients in prone position decreased mortality, the standard approach to prone position has been the use of daily sessions of 16 to 20 hours. With this approach most patients usually require 3 to 4 prone sessions (intermittent daily prone position). However, due to the excessive workload of ICU staff during the Covid-19 pandemics, several centers decided to extend the sessions beyond 24 hours to decrease the frequency of position changes in patients with Covid-19 associated ARDS. Several centers reported their experience with prolonged sessions showing that it was feasible and that the rate of adverse events appeared to be similar to those previously reported with the standard daily sessions. The largest experience reported up to now was a retrospective study which included 417 patients from 15 centers in Chile, where a continuous prolonged prone position was applied as a nationwide strategy (Cornejo 2022). Most patients required a single prone session of 4 (3-5) days. Although the study lacked a control group, the mortality and rate of adverse events was rather low compared to other series of patients with similar characteristics. A non-randomized controlled study from 3 hospital in US even showed that compared to patients treated with standard prone sessions (\< 24 hours), patients treated with prolonged sessions had a lower risk of mortality (Okin 2023). However, other reports have shown conflicting results regarding the potential benefit associated to prolonging prone position sessions beyond 24 hours. Recent guidelines have acknowledged that the optimal duration of prone position sessions is unknown and must be further investigated (Grasselli 2023). Prolonging prone position sessions may ensure that this lung protective intervention is maintained throughout the acute phase of ARDS.

The goal of the present study is to compare the effects of a continuous prolonged prone position versus an intermittent daily prone position on mortality and other relevant outcomes, as well as on the incidence of adverse events potentially related to prone position, in mechanically ventilated patients with moderate-to-severe ARDS.

The study will be a randomized, multicenter, two-arm parallel-group, investigator-led clinical trial with allocation concealment and intention-to-treat analysis. Patients allocated to the experimental arm (prolonged prone position) will receive prone position sessions for a minimum of 48 hours, which will be further extended until PaO2/FiO2 is ≥ 200, or until reaching the maximum of 120 hours. Patients allocated to the control arm (intermittent prone position) will receive prone position sessions for a minimum of 16 hours and a maximum of 24 hours. In both groups prone sessions may be repeated if PaO2/FiO2 ratio falls below 150 after being returned to supine position during the first 7 days (intervention period).

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years
* Endotracheal intubation and mechanical ventilation for less than 72 hours
* Moderate-severe ARDS defined as:

  1. Within 1 week of a known clinical insult or new or worsening respiratory symptoms
  2. Bilateral infiltrates not fully explained by effusions, lobar/lung collapse, or nodules
  3. Respiratory failure not fully explained by cardiac failure or fluid overload
  4. PaO2/FiO2 \< 150 mmHg in supine position
* Prone positioning has been indicated by the attending physician, OR has already been initiated within the last 16 hours

Exclusion Criteria:

* Contraindications for prone positioning such as intracranial pressure \> 20 mmHg, massive hemoptysis, recent tracheal surgery or sternotomy or abdominal surgery with an open wound, recent facial trauma or facial surgery, unstable spine, femur, or pelvic fractures, or a single anterior chest tube with air leaks
* Patient on extracorporeal membrane oxygenation (ECMO) before randomization
* Chronic respiratory failure requiring oxygen therapy or non-invasive ventilation (NIV)
* Known pregnancy
* Anticipating withdrawal of life support or shift to palliative care

Primary outcomes:
measure: 28-day mortality
timeFrame: 28 days
Secondary outcomes:
measure: 90-day mortality
timeFrame: 90 days
measure: Ventilator-free days
timeFrame: 28 days
measure: ICU-free days
timeFrame: 28 days
measure: Hospital-free days at day 28
timeFrame: 28 days
measure: Number of patients who required rescue procedures
timeFrame: 28 days
measure: Number of patients with Pneumothorax
timeFrame: 7 days
measure: Occurrence of new pressure sores
timeFrame: Days 3 and 7
measure: Adverse events
timeFrame: 7 days
Other outcomes:
Locations:
city: Concepción
country: Chile
facility: Hospital Guillermo Grant Benavente
city: Los Ángeles
country: Chile
facility: Complejo Asistencial Dr. Victor Ríos Ruiz
city: Quilpué
country: Chile
facility: Hospital de Quilpué
city: Santiago
country: Chile
facility: Clínica Las Condes
city: Santiago
country: Chile
facility: Hospital Clínico UC Christus
city: Santiago
country: Chile
facility: Hospital Clínico Universidad de Chile
Study officials:
affiliation: Pontifiia Universidad Catolica de Chile
name: Alejandro Bruhn, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Chile
name: Rodrigo Cornejo, MD, MBA
role: STUDY_DIRECTOR
References:
citation: Cornejo RA, Montoya J, Gajardo AIJ, Graf J, Alegria L, Baghetti R, Irarrazaval A, Santis C, Pavez N, Leighton S, Tomicic V, Morales D, Ruiz C, Navarrete P, Vargas P, Galvez R, Espinosa V, Lazo M, Perez-Araos RA, Garay O, Sepulveda P, Martinez E, Bruhn A; SOCHIMI Prone-COVID-19 Group. Continuous prolonged prone positioning in COVID-19-related ARDS: a multicenter cohort study from Chile. Ann Intensive Care. 2022 Nov 28;12(1):109. doi: 10.1186/s13613-022-01082-w.
citation: Guerin C, Reignier J, Richard JC, Beuret P, Gacouin A, Boulain T, Mercier E, Badet M, Mercat A, Baudin O, Clavel M, Chatellier D, Jaber S, Rosselli S, Mancebo J, Sirodot M, Hilbert G, Bengler C, Richecoeur J, Gainnier M, Bayle F, Bourdin G, Leray V, Girard R, Baboi L, Ayzac L; PROSEVA Study Group. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med. 2013 Jun 6;368(23):2159-68. doi: 10.1056/NEJMoa1214103. Epub 2013 May 20.
citation: Grasselli G, Calfee CS, Camporota L, Poole D, Amato MBP, Antonelli M, Arabi YM, Baroncelli F, Beitler JR, Bellani G, Bellingan G, Blackwood B, Bos LDJ, Brochard L, Brodie D, Burns KEA, Combes A, D'Arrigo S, De Backer D, Demoule A, Einav S, Fan E, Ferguson ND, Frat JP, Gattinoni L, Guerin C, Herridge MS, Hodgson C, Hough CL, Jaber S, Juffermans NP, Karagiannidis C, Kesecioglu J, Kwizera A, Laffey JG, Mancebo J, Matthay MA, McAuley DF, Mercat A, Meyer NJ, Moss M, Munshi L, Myatra SN, Ng Gong M, Papazian L, Patel BK, Pellegrini M, Perner A, Pesenti A, Piquilloud L, Qiu H, Ranieri MV, Riviello E, Slutsky AS, Stapleton RD, Summers C, Thompson TB, Valente Barbas CS, Villar J, Ware LB, Weiss B, Zampieri FG, Azoulay E, Cecconi M; European Society of Intensive Care Medicine Taskforce on ARDS. ESICM guidelines on acute respiratory distress syndrome: definition, phenotyping and respiratory support strategies. Intensive Care Med. 2023 Jul;49(7):727-759. doi: 10.1007/s00134-023-07050-7. Epub 2023 Jun 16.
citation: Okin D, Huang CY, Alba GA, Jesudasen SJ, Dandawate NA, Gavralidis A, Chang LL, Moin EE, Ahmad I, Witkin AS, Hardin CC, Hibbert KA, Kadar A, Gordan PL, Lee H, Thompson BT, Bebell LM, Lai PS. Prolonged Prone Position Ventilation Is Associated With Reduced Mortality in Intubated COVID-19 Patients. Chest. 2023 Mar;163(3):533-542. doi: 10.1016/j.chest.2022.10.034. Epub 2022 Nov 4.