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

Not Applicable

Recruiting

• Conditions: Acute Respiratory Distress Syndrome

• Registration Number: NCT06854627
• Lead Sponsor: Pontificia Universidad Catolica de Chile

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).

Study Timeline

• Study First Submitted: 2025-01-21
• Study First Submitted QC: 2025-02-25
• Study First Posted: 2025-03-03
• Status Verified: 2025-04
• Study Start: 2025-04-07
• Last Update Submitted: 2025-04-11
• Last Update Posted: 2025-04-16
• Primary Completion: 2027-10
• Study Completion: 2028-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 780

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
28-day mortality	28 days	All-cause mortality

Secondary Outcome Measures

Name	Time	Method
90-day mortality	90 days	All-cause mortality
Ventilator-free days	28 days	Days-free from mechanical ventilation and alive up to day 28
ICU-free days	28 days	Days-free from ICU and alive up to day 28
Hospital-free days at day 28	28 days	Days-free from Hospital and alive up to day 28
Number of patients who required rescue procedures	28 days	Use of rescue procedures for ARDS (ECMO or ECCOR2)
Number of patients with Pneumothorax	7 days	Number of patients with a new onset of pneumothorax
Occurrence of new pressure sores	Days 3 and 7	Occurrence of new pressure sores including their location and severity
Adverse events	7 days	displacement of endotracheal tube, vascular catheters, or gastric tube; endotracheal tube obstruction, unplanned extubation, arterial oxygen , displacement of invasive devices, hypoxemia, arterial hypotension, bradycardia, cardiac arrest

Trial Locations

Locations (6)

Hospital de Quilpué; 🇨🇱 Quilpué, Chile

Hospital Clínico UC Christus; 🇨🇱 Santiago, Chile

Hospital Clínico Universidad de Chile; 🇨🇱 Santiago, Chile

Hospital Guillermo Grant Benavente; 🇨🇱 Concepción, Chile

Clínica Las Condes; 🇨🇱 Santiago, Chile

Complejo Asistencial Dr. Victor Ríos Ruiz; 🇨🇱 Los Ángeles, Chile