Prone Positioning and Spontaneous Breathing (PROSE)

Prone Positioning and Spontaneous Breathing: a Feasibility Study

Spontaneous breathing during mechanical ventilation has been recommended in patients with ARDS and is currently used. in part because oxygenation is better and there is a lower risk of diaphragm dysfunction due to disuse. The other approach to minimizing lung injury from spontaneous effort is the use of neuromuscular blockade; an early and short term (48 hours) of neuromuscular blockade in patients with severe ARDS has been shown to decrease inflammation and to improve survival. The investigators propose a pilot study to test the feasibility and the physiological effects of allowing spontaneous breathing in the prone position in patients with ARDS.

Study Overview

• Status: Unknown
• Conditions: Critical Illness; ARDS
• Intervention / Treatment: Procedure: Supine + spontaneous effort; Procedure: Supine + paralysis; Procedure: Prone + paralysis; Procedure: Prone + spontaneous breathing

Detailed Description

The multi-center feasibility study will enroll 12 adult ARDS patients from the Intensive Care Units (ICUs) in Japan and Peru. Informed consent will be obtained from the patient or legally authorized substitute decision maker. Moderate-to-severe ARDS patients who are planned to turn to prone positioning, based on the attending physician's decisions will be included. Prior to initiating the protocol, patients will be sedated deeply with sedatives and/or opioids. Ventilator settings, physiological data, esophageal pressure and diaphragm activity will be recorded and physiological measurements will be collected for 5 minutes in supine (Measurement 1: Supine + spontaneous effort) . Patients will be paralyzed with a continuous infusion of rocuronium, and Measurement 2 (Supine + paralysis) will be recorded. The critical care team in the ICU change the position from supine to prone. After waiting for at least 1 hour in prone positioning, Measurement 3 (Prone + paralysis) will be recorded. Continuous infusion of rocuronium will be gradually decreased (and can be terminated) until spontaneous breathing will be observed without reaching an excessive level. The presence of spontaneous breathing will be evaluated by the negative swing of esophageal pressure, and Measurement 5 (Prone + spontaneous breathing) will be recorded.

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Osaka
    • Suita, Osaka, Japan, 565-0871
      • Osaka University Hospital

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:

• Patients ≧ 18 years old
• Patients with moderate-to-severe ARDS as per the Berlin definition
• Patients with esophageal balloon manometry
• Patients planned to turn to prone positioning, based on the attending physician's decisions

Exclusion Criteria:

• Contraindication for prone positioning, referring to a previous randomized clinical trial

  1. Intracranial pressure >30 mm Hg or cerebral perfusion pressure <60 mmHg
  2. Massive hemoptysis requiring an immediate surgical or interventional radiology procedure
  3. Tracheal surgery or sternotomy during the previous 15 days
  4. Serious facial trauma or facial surgery during the previous 15 days
  5. Cardiac pacemaker inserted in the last 2 days
  6. Unstable spine, femur, or pelvic fractures
• Major hemodynamic instability:

Mean arterial pressure lower than 60 mm Hg despite adequate fluid resuscitation and two vasopressors or increase of vasopressor dose by 30% in the previous 6 hours.

• Contraindication to EIT electrode placement Burns, chest wall bandaging limiting electrode placement, pacemaker
• Clinical judgement of the attending physician against proning and/or spontaneous breathing

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: study arm; all patients will receive all four intervention in the same sequential method	Procedure: Supine + spontaneous effort; without muscle paralysis in supine position; Procedure: Supine + paralysis; administer muscle paralysis in supine position; Procedure: Prone + paralysis; change the patient position from supine to prone with muscle paralysis; Procedure: Prone + spontaneous breathing; cease the paralysis in supine position

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
spontaneous breathing	The intensity of spontaneous breathing during supine vs. prone estimated by an esophageal manometry	Through study completion (up to 24 hours)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
inflammatory cytokines	IL-6 levels	Through study completion (up to 24 hours)
Trans-pulmonary pressure	Trans-pulmonary pressure	Through study completion (up to 24 hours)
electrical activity of diaphragm	electrical activity of diaphragm	Through study completion (up to 24 hours)
gas exchange	gas exchange	Through study completion (up to 24 hours)

Collaborators and Investigators

• Sponsor: Osaka University
• Collaborators: Hospital Rebagliati
• Investigators: Principal Investigator: Takeshi Yoshida, PhD, Osaka University

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2019
• Primary Completion (Actual): May 8, 2020
• Study Completion (Anticipated): March 31, 2021

Study Registration Dates

• First Submitted: November 15, 2018
• First Submitted That Met QC Criteria: December 5, 2018
• First Posted (Actual): December 7, 2018

Study Record Updates

• Last Update Posted (Actual): May 15, 2020
• Last Update Submitted That Met QC Criteria: May 13, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: prone position; spontaneous breathing; muscle paralysis
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Critical Illness
• Other Study ID Numbers: PROSE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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