COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC:

Get the latest research information from NIH: Menu

Prone Positioning and Spontaneous Breathing (PROSE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03768154
Recruitment Status : Active, not recruiting
First Posted : December 7, 2018
Last Update Posted : May 15, 2020
Hospital Rebagliati
Information provided by (Responsible Party):
Osaka University

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Critical Illness ARDS Procedure: Supine + spontaneous effort Procedure: Supine + paralysis Procedure: Prone + paralysis Procedure: Prone + spontaneous breathing Phase 1

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Intervention Model: Sequential Assignment
Intervention Model Description: Measurement 1 (Supine + spontaneous effort) , Measurement 2 (Supine + paralysis) , Measurement 3 (Prone + paralysis) , Measurement 4 (Prone + spontaneous breathing)
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Prone Positioning and Spontaneous Breathing: a Feasibility Study
Actual Study Start Date : March 1, 2019
Actual Primary Completion Date : May 8, 2020
Estimated Study Completion Date : March 31, 2021

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

Primary Outcome Measures :
  1. spontaneous breathing [ Time Frame: Through study completion (up to 24 hours) ]
    The intensity of spontaneous breathing during supine vs. prone estimated by an esophageal manometry

Secondary Outcome Measures :
  1. inflammatory cytokines [ Time Frame: Through study completion (up to 24 hours) ]
    IL-6 levels

  2. Trans-pulmonary pressure [ Time Frame: Through study completion (up to 24 hours) ]
    Trans-pulmonary pressure

  3. electrical activity of diaphragm [ Time Frame: Through study completion (up to 24 hours) ]
    electrical activity of diaphragm

  4. gas exchange [ Time Frame: Through study completion (up to 24 hours) ]
    gas exchange

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03768154

Layout table for location information
Osaka University Hospital
Suita, Osaka, Japan, 565-0871
Sponsors and Collaborators
Osaka University
Hospital Rebagliati
Layout table for investigator information
Principal Investigator: Takeshi Yoshida, PhD Osaka University
Layout table for additonal information
Responsible Party: Osaka University Identifier: NCT03768154    
Other Study ID Numbers: PROSE
First Posted: December 7, 2018    Key Record Dates
Last Update Posted: May 15, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Osaka University:
spontaneous breathing
prone position
muscle paralysis
Additional relevant MeSH terms:
Layout table for MeSH terms
Respiratory Aspiration
Critical Illness
Respiration Disorders
Respiratory Tract Diseases
Pathologic Processes
Disease Attributes