PRone positioN in Patients With spontanEous ventiLation and Acute Hypoxemic respIratory FailurE (PRONELIFE)

The proposed randomized controlled trial aims at comparing the application of the prone position in spontaneously breathing patients with acute hypoxemic respiratory failure from any cause versus standard treatment on the rate of invasive mechanical ventilation or all-cause of mortality. The secondary endpoints will include time to tracheal intubation and effects of awake proning on the oxygenation parameters, dyspnea sensation, complications, and tolerance. Other endpoints are ventilation free-days at 28 days, duration of invasive ventilation, length of ICU and hospital stay, ICU and hospital mortality, and 28, 60, and 90-day mortality.

Study Overview

• Status: Suspended
• Conditions: Respiratory Failure With Hypoxia; Respiratory Failure Without Hypercapnia
• Intervention / Treatment: Other: Prone Position

Detailed Description

The investigators intend to recruit acute hypoxemic respiratory failure patients with a respiratory rate of more than 25 breaths per minute, SpO2 < 94% and FiO2 of at least 40% or more by either Venturi facemask, HFNC, or NIV/CPAP and, absence of decompensated respiratory acidosis during two years. Currently, the investigators expect about 35 centers to participate in the trial.

Demographic data and clinical characteristics on screened patients, regardless of enrolment criteria match, will be recorded (registry). The investigators will randomize 650 patients admitted to the participating centers' intensive care units and expect each participating center to randomize at least 25 patients who meet all inclusion criteria.

• Study Type: Interventional
• Enrollment (Anticipated): 650
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Barcelona
    • Sabadell, Barcelona, Spain, 08208
      • I3PT Institut d'Investigació i Innovació Parc Taulí

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria

• >18 years
• Acute respiratory failure from any cause
• Admitted to a participating ICU
• Written informed consent

Exclusion criteria

• Presence of any contraindication to prone position (APPENDIX i)
• The patient meets the criteria for intubation (see item 7.2.3)
• Participating in other interventional studies with the same primary outcome
• Receiving comfort care only
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Prone position; Patients with acute hypoxemic respiratory failure from any cause	Other: Prone Position; The best-fitting and most-tolerated oxygen interface will be used in the prone position--this could be different from patient to patient, and different from what is used in the supine position, and could differ between patients but also institutions (i.e., depending on the availability of masks with or without a reservoir bag and with or without the Venturi system, HFNO, CPAP or NIV). The patient will be placed in the prone position for at least 2 hours, which may be prolonged if the patient is comfortable or interrupted if the patient presents any criteria for prone position discontinuation. After the prone position period, the patient will be rotated to the semi-recumbent supine position for at least 2 hours and a maximum of 4 hours. This 2-hour time frame will depend on nursing availability, need for hygiene, complementary explorations, or diet.
NO_INTERVENTION: Supine position; Patients with acute hypoxemic respiratory failure from any cause

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Composite endpoint comprising the rate of tracheal intubation or all-cause of mortality during the first fourteen days of enrolment.	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality at day 14	Effect of prone position on mortality	14 days
Intubation among survivors at day 24	Effect of prone position on the rate of intubation	24 days
Effects on oxygenation defined by the SpO2	Effects of prone position on oxygenation	4 hours
Days under the oxygen support device	Days under the oxygen support device (HFNC, NIV, non-rebreather mask, Venturi mask) The VAS is a straight horizontal line of fixed length. The ends are defined as the extreme limits of the parameter to be measured (symptom,pain,health) orientated from the left (worst) to the right (best).	28 days
Dyspnea	Effects of prone position on dyspnea, defined according modified Borg dyspnea scale. This is a scale rates the difficulty of breathing. It starts at number 0 where dyspnea is causing no difficulty at all and progresses through to number 10 where dyspnea is maximal.	4 hours
Time to tracheal intubation	Effects of prone position on timing for tracheal intubation	14 days
Rate of complications related to prone position	Effects of prone position on adverse effects such Oxygen desaturations (SpO2 <90%); Episodes of hemodynamic instability (BPsys < 90mmHg or BPsys drop > 10mmHg if BPsys < 90 before the maneuver); Need of orotracheal intubation; Cardiac arrest; Displacement of the non-invasive respiratory support device; Removal of central venous line, if documented; Displacement of an arterial line, if documented; Displacement of a urinary catheter, if documented	4 hours
Respiratory rate	Effects of prone position of respiratory rate	4 hours
Duration of invasive mechanical ventilation	Duration of invasive mechanical ventilation in those patients who required intubation	90 days
Ventilation-free days (VFD) at 28 days from ICU admission,	Ventilation-free days (VFD) at 28 days from ICU admission, defined as the number of days alive and free from IMV during the first 28 days from start of IMV	28 days
ICU-free days and hospital-free days	ICU-free days and hospital-free days at day 90	90 days
Mortality	Mortality at day 28 and day 90	28 and 90 days

Collaborators and Investigators

• Sponsor: Corporacion Parc Tauli
• Investigators: Principal Investigator: Antonio Artigas, MD, PhD, I3PT Institut d'Investigació i Innovació Parc Taulí

Publications and helpful links

General Publications

• Frat JP, Thille AW, Mercat A, Girault C, Ragot S, Perbet S, Prat G, Boulain T, Morawiec E, Cottereau A, Devaquet J, Nseir S, Razazi K, Mira JP, Argaud L, Chakarian JC, Ricard JD, Wittebole X, Chevalier S, Herbland A, Fartoukh M, Constantin JM, Tonnelier JM, Pierrot M, Mathonnet A, Beduneau G, Deletage-Metreau C, Richard JC, Brochard L, Robert R; FLORALI Study Group; REVA Network. High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N Engl J Med. 2015 Jun 4;372(23):2185-96. doi: 10.1056/NEJMoa1503326. Epub 2015 May 17.
• 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.
• Scaravilli V, Grasselli G, Castagna L, Zanella A, Isgro S, Lucchini A, Patroniti N, Bellani G, Pesenti A. Prone positioning improves oxygenation in spontaneously breathing nonintubated patients with hypoxemic acute respiratory failure: A retrospective study. J Crit Care. 2015 Dec;30(6):1390-4. doi: 10.1016/j.jcrc.2015.07.008. Epub 2015 Jul 16.
• Riera J, Perez P, Cortes J, Roca O, Masclans JR, Rello J. Effect of high-flow nasal cannula and body position on end-expiratory lung volume: a cohort study using electrical impedance tomography. Respir Care. 2013 Apr;58(4):589-96. doi: 10.4187/respcare.02086.
• Morales-Quinteros L, Schultz MJ, Serpa-Neto A, Antonelli M, Grieco DL, Roca O, Juffermans NP, de Haro C, de Mendoza D, Blanch L, Camprubi-Rimblas M, Goma G, Artigas-Raventos A; PRONELIFE collaborative group. Awake prone positioning in nonintubated spontaneous breathing ICU patients with acute hypoxemic respiratory failure (PRONELIFE)-protocol for a randomized clinical trial. Trials. 2022 Jan 10;23(1):30. doi: 10.1186/s13063-021-05991-2.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 7, 2022
• Primary Completion (ANTICIPATED): November 1, 2023
• Study Completion (ANTICIPATED): November 1, 2023

Study Registration Dates

• First Submitted: October 25, 2019
• First Submitted That Met QC Criteria: October 25, 2019
• First Posted (ACTUAL): October 29, 2019

Study Record Updates

• Last Update Posted (ACTUAL): October 13, 2022
• Last Update Submitted That Met QC Criteria: October 11, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Prone position; Acute Respiratory Failure
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Respiratory Insufficiency; Hypoxia; Hypercapnia
• Other Study ID Numbers: 2019/68-UCI-HUSC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data for all primary and secondary outcome measures will be made available
• IPD Sharing Time Frame: Data will be available within 6 months of study completion
• IPD Sharing Access Criteria: Data access request will be reviewed by an External Independent Review Panel. Requestors will be required to signed a Data Access Agreement
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No