Effect of Continuous Prolonged Prone Position Versus Intermittent Daily Prone Position in ARDS

NCT ID: NCT06854627

Last Updated: 2025-12-02

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 780 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-04-07
• Study Completion Date: 2028-01-31

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).

Conditions

Acute Respiratory Distress Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: SINGLE

Study Groups

Intermittent Prone Position

This arm will receive prone position sessions as applied in the PROSEVA trial (Guerin 2013)

Group Type: ACTIVE_COMPARATOR

Daily prone position sessions

Intervention Type: PROCEDURE

Prone position sessions will be extended at least 16 hours, but no longer than 24 hours. Prone sessions will be repeated if PaO2/FiO2 ratio decreases to \< 150 after returning to supine position within the first 7 days after randomization. The extension of repeated prone sessions will follow the same criteria.

Prolonged Prone Position

This arm will receive prone position sessions as applied in a previous multicenter study during the COVID-19 pandemics (Cornejo 2022)

Group Type: EXPERIMENTAL

Prolonged prone position sessions

Intervention Type: PROCEDURE

Prone position sessions will be extended at least 48 hours AND until PaO2/FiO2 ratio is ≥ 200, but no longer than 120 hours. Prone sessions will be repeated if PaO2/FiO2 ratio decreases to \< 150 after returning to supine position within the first 7 days after randomization. The extension of repeated prone sessions will follow the same criteria.

Interventions

Daily prone position sessions

Prone position sessions will be extended at least 16 hours, but no longer than 24 hours. Prone sessions will be repeated if PaO2/FiO2 ratio decreases to \< 150 after returning to supine position within the first 7 days after randomization. The extension of repeated prone sessions will follow the same criteria.

Intervention Type: PROCEDURE

Prolonged prone position sessions

Prone position sessions will be extended at least 48 hours AND until PaO2/FiO2 ratio is ≥ 200, but no longer than 120 hours. Prone sessions will be repeated if PaO2/FiO2 ratio decreases to \< 150 after returning to supine position within the first 7 days after randomization. The extension of repeated prone sessions will follow the same criteria.

Intervention Type: PROCEDURE

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospital do Coracao

OTHER

Sponsor Role: collaborator

Fundacion Clinica Valle del Lili

OTHER

Sponsor Role: collaborator

Fondo Nacional de Desarrollo Científico y Tecnológico, Chile

OTHER_GOV

Sponsor Role: collaborator

Pontificia Universidad Catolica de Chile

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alejandro Bruhn, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Pontifiia Universidad Catolica de Chile

Rodrigo Cornejo, MD, MBA

Role: STUDY_DIRECTOR

University of Chile

Locations

Hospital Guillermo Grant Benavente

Concepción, , Chile

Site Status: RECRUITING

Complejo Asistencial Dr. Victor Ríos Ruiz

Los Ángeles, , Chile

Site Status: RECRUITING

Hospital de Quilpué

Quilpué, , Chile

Site Status: RECRUITING

Clínica Las Condes

Santiago, , Chile

Site Status: RECRUITING

Hospital Clínico UC Christus

Santiago, , Chile

Site Status: RECRUITING

Hospital Clínico Universidad de Chile

Santiago, , Chile

Site Status: RECRUITING

Countries

Chile

Central Contacts

Alejandro Bruhn, MD, PhD

Role: CONTACT

abruhn@uc.cl

+56223543292

Eduardo Kattan, MD, PhD

Role: CONTACT

e.kattan@gmail.com

994793024

Facility Contacts

Paula Fernández, MD

Role: primary

fernandezandrade@gmail.com

Fernando Tirapegui, MD

Role: primary

ftirapegui@uc.cl

Mario Bruna, MD

Role: primary

mbrunap74@gmail.com

Martín Benites, MD, PhD(c)

Role: primary

benitesmartinh@gmail.com

Roque Basoalto, PT, PhD

Role: primary

roque.basoalto@gmail.com

Rodrigo Cornejo, MD

Role: primary

rcornejor@hcuch.cl

References

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.

Reference Type: BACKGROUND

PMID: 36441352 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 23688302 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 37326646 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 36343687 (View on PubMed)

Other Identifiers

230606007

Identifier Type: -

Identifier Source: org_study_id