Breathing Effort in Covid-19 Pneumonia: Effects of Positive Pressure, Inspired Oxygen Fraction and Decubitus

May 12, 2021 updated by: Pietro Caironi, San Luigi Gonzaga Hospital

Dynamic Transpulmonary Pressure in Covid-19 Pneumonia: Effects of Positive Pressure, Inspired Oxygen Fraction and Decubitus

The study investigates the role of positive pressure, inspired oxygen fraction and different decubiti (seated, supine, prone) on breathing effort (as assessed by esophageal pressure swings) in Covid-19 pneumonia (at different disease stages) and in other causes of respiratory failure. The hypothesis is that positive pressure might be deleterious in terms of breathing effort if the main pathological mechanism associated with Sars-CoV-2 infection in the lung is not alveolar damage (as in other causes of respiratory failure) but vascular impairment as previously reported. The effects of high inspired oxygen fractions and decubiti might also be different with respect to other causes of respiratory failure.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

In spite of the overwhelming numbers of the current pandemic, many questions remain open regarding the pathophysiology of Covid-19 associated pneumonia. While some features of the disease (such as the oxygenation improvement associated with proning and/or continuous positive airway pressure) seem to line up with other causes of pneumonia characterized by primary alveolar damage, specific characteristics have been reported about Sars-CoV-2 lung infection which suggest a certain degree of parenchymal preservation and a predominant role of vascular impairment: the dissociation between lung volume and gas exchange, and the so called "happy hypoxemia" both evoke the possibility of mechanisms other than the loss of aeration as causes of hypoxia. Accordingly, evidence are now growing on the role of vascular dysregulation in this regard. It is probable, as previously put forward, that different stages exist in the disease which may account for the discordant findings of previous studies seeking to either associate or separate Covid-19 pneumonia and other causes of respiratory failure. In the present study we will compare the effects of three currently used approaches to improve gas exchange (continuous positive airway pressure, external oxygen administration and decubiti variations) in three different populations (1) early Covid-19 pneumonia, 2) severe late Covid-19 pneumonia and 3) non-Covid-19 pneumonia) in terms of breathing effort as assessed by esophageal pressure swings: our aim is to evaluate, in these populations, the real benefits (beyond the previously reported ones on gas exchange) of such strategies on lung rest. Our hypothesis is that, at least in the early stages of Covid-19 (and as opposed to other causes of respiratory failure), the application of positive pressure might be deleterious if no potential for recruitment, but rather a primary vascular impairment, is associated with hypoxia. If this will be the case the same (or a similar) degree of oxygenation improvement and a safer pattern of ventilation might be attained with the simple administration of oxygen or decubiti variations without the application of positive pressure, thus completely changing the current standards for the treatment of Covid-19 pneumonia.

Study Type

Interventional

Enrollment (Anticipated)

72

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Italy
    • Italy/Turin
      • Orbassano, Italy/Turin, Italy, 10043
        • Recruiting
        • A.O.U. San Luigi Gonzaga di Orbassano
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

Group 1 (Covid-19 early pneumonia)

  • Age > 18
  • Positive Sars-CoV 2 nasal swab
  • interstitial pneumonia at either CT scan or chest X-ray
  • Respiratory failure requiring CPAP for less than 48 hours
  • FiO2 ≤0.5 and CPAP≤10 cmH2O

Group 2 (Covid-19 severe pneumonia)

  • Age > 18
  • Positive Sars-CoV 2 nasal swab
  • interstitial pneumonia at either CT scan or chest X-ray
  • Respiratory failure requiring CPAP

  • Signs of severity with CPAP 10 cmH2O and FiO2 0.5: pulse oximetry (SpO2) ≤ 93% associated to either:

    • Dyspnea
    • Two or more signs of increased respiratory effort (respiratory rate ≥25 bpm, use of accessory inspiratory muscles , tirage, intercostal space depression, nasal flaring, expiratory abdominal efforts, PaCO2 < 35)

Group 3 (Non Covid-19 pneumonia)

  • Age > 18
  • Negative Sars-CoV 2 nasal swab
  • CT scan or chest X-ray non compatible with Covid-19 associated pneumonia
  • Respiratory failure requiring CPAP

Exclusion Criteria:

Group 1 (Covid-19 early pneumonia)

  • Concomitant chronic pulmonary disease
  • Chronic heart failure New York Heart Association (NYHA) 3-4
  • Bacterial pulmonary associated infection (diagnosed or suspected)
  • Pulmonary embolism
  • Acute cardiogenic pulmonary edema

  • Signs of severity with CPAP 10 cmH2O and FiO2 0.5: SpO2≤ 93% associated to either:

    • Dyspnea
    • Two or more signs of increased respiratory effort (respiratory rate ≥25 bpm, use of accessory inspiratory muscles , tirage, intercostal space depression, nasal flaring, expiratory abdominal efforts, PaCO2 < 35)
  • At least one sign of respiratory fatigue/decompensation (pH<7.30 with PaCO2 >45, respiratory rate <15 bpm, paradoxal abdominal breathing, mental status alteration)

Group 2 (Covid-19 severe pneumonia)

  • Concomitant chronic pulmonary disease
  • Chronic heart failure NYHA 3-4
  • Bacterial pulmonary associated infection (diagnosed or suspected)
  • Pulmonary embolism
  • Acute cardiogenic pulmonary edema
  • At least one sign of respiratory fatigue/decompensation (pH<7.30 with PaCO2 >45, respiratory rate <15 bpm, paradoxal abdominal breathing, mental status alteration)

Group 3 (Non Covid-19 pneumonia)

  • Concomitant chronic pulmonary disease
  • Chronic heart failure NYHA 3-4
  • Bacterial pulmonary associated infection (diagnosed or suspected)
  • Pulmonary embolism
  • Acute cardiogenic pulmonary edema
  • At least one sign of respiratory fatigue/decompensation (pH<7.30 with PaCO2 >45, respiratory rate <15 bpm, paradoxal abdominal breathing, mental status alteration)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Spontaneous breathing, Venturi Mask FiO2 0.5, seated decubitus
Patient will be evaluated after 20 minutes of spontaneous breathing, with FiO2 0.5 (Venturi Mask), during seated decubitus. Respiratory, haemodynamics, and data on blood gas analysis will be obtained.
Device: Esophageal catheter
Patients are equipped with an esophageal catheter: positioning is performed after accurate nasopharyngeal anesthesia with lidocaine
Experimental: Spontaneous breathing, Non Rebreathing Mask, seated decubitus
Patient will be evaluated after 20 minutes of spontaneous breathing, with FiO2 1 (Non Rebreathing Mask), during seated decubitus. Respiratory, haemodynamics, and data on blood gas analysis will be obtained.
Device: Esophageal catheter
Patients are equipped with an esophageal catheter: positioning is performed after accurate nasopharyngeal anesthesia with lidocaine
Experimental: Continuous Positive Airway Pressure (CPAP) 7 cmH2O, FiO2 0.5, seated decubitus
Patient will be evaluated after 20 minutes of CPAP (7 cmH2O), with FiO2 0.5, during seated decubitus. Respiratory, haemodynamics, and data on blood gas analysis will be obtained.
Device: Esophageal catheter
Patients are equipped with an esophageal catheter: positioning is performed after accurate nasopharyngeal anesthesia with lidocaine
Experimental: Continuous Positive Airway Pressure (CPAP) 7 cmH2O, FiO2 0.5, supine decubitus
Patient will be evaluated after 20 minutes of CPAP (7 cmH2O), with FiO2 0.5, during supine decubitus. Respiratory, haemodynamics, and data on blood gas analysis will be obtained.
Device: Esophageal catheter
Patients are equipped with an esophageal catheter: positioning is performed after accurate nasopharyngeal anesthesia with lidocaine
Experimental: Continuous Positive Airway Pressure (CPAP) 7 cmH2O, FiO2 0.5, prone decubitus
Patient will be evaluated after 20 minutes of CPAP (7 cmH2O), with FiO2 0.5, during prone decubitus. Respiratory, haemodynamics, and data on blood gas analysis will be obtained.
Device: Esophageal catheter
Patients are equipped with an esophageal catheter: positioning is performed after accurate nasopharyngeal anesthesia with lidocaine
Experimental: Continuous Positive Airway Pressure (CPAP) 7 cmH2O, FiO2 1, seated decubitus
Patient will be evaluated after 20 minutes of CPAP (7 cmH2O), with FiO2 1.0, during seated decubitus. Respiratory, haemodynamics, and data on blood gas analysis will be obtained.
Device: Esophageal catheter
Patients are equipped with an esophageal catheter: positioning is performed after accurate nasopharyngeal anesthesia with lidocaine
Experimental: Continuous Positive Airway Pressure (CPAP) 12 cmH2O, FiO2 0.5, seated decubitus
Patient will be evaluated after 20 minutes of CPAP (12 cmH2O), with FiO2 0.5, during seated decubitus. Respiratory, haemodynamics, and data on blood gas analysis will be obtained.
Device: Esophageal catheter
Patients are equipped with an esophageal catheter: positioning is performed after accurate nasopharyngeal anesthesia with lidocaine
Experimental: Continuous Positive Airway Pressure (CPAP) 12 cmH2O, FiO2 1, seated decubitus
Patient will be evaluated after 20 minutes of CPAP (7 cmH2O), with FiO2 1.0, during seated decubitus. Respiratory, haemodynamics, and data on blood gas analysis will be obtained.
Device: Esophageal catheter
Patients are equipped with an esophageal catheter: positioning is performed after accurate nasopharyngeal anesthesia with lidocaine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Esophageal pressure swings at different levels of positive end-expiratory pressure (PEEP)
Time Frame: 160 minutes
The main outcome of the study is represented by the difference in esophageal pressure swings (expiratory minus inspiratory) between the three levels of end expiratory pressure applied (0-7-12 cmH2O)
160 minutes

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Esophageal pressure swings at different levels of inspired oxygen fraction
Time Frame: 160 minutes
One of the secondary outcomes of the study is represented by the difference in esophageal pressure swings (expiratory minus inspiratory) between the two levels of FiO2 applied (0.5-1)
160 minutes
Esophageal pressure swings at different decubiti
Time Frame: 160 minutes
One of the secondary outcomes of the study is represented by the difference in esophageal pressure swings (expiratory minus inspiratory) between the three decubiti applied (seated, supine, prone)
160 minutes

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

San Luigi Gonzaga Hospital

Investigators

  • Principal Investigator: Pietro Caironi, MD, San Luigi Gonzaga Hospital
  • Principal Investigator: Lorenzo Giosa, MD, San Luigi Gonzaga Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2021

Primary Completion (Anticipated)

August 1, 2021

Study Completion (Anticipated)

August 1, 2021

Study Registration Dates

First Submitted

May 11, 2021

First Submitted That Met QC Criteria

May 11, 2021

First Posted (Actual)

May 13, 2021

Study Record Updates

Last Update Posted (Actual)

May 14, 2021

Last Update Submitted That Met QC Criteria

May 12, 2021

Last Verified

May 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2782 (Sir Halley Stewart Trust)

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

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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