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

Primary Purpose

COVID-19 Pneumonia

Status

Unknown status

Phase

Not Applicable

Locations

Italy

Study Type

Interventional

Intervention

Esophageal catheter

About this trial

This is an interventional other trial for COVID-19 Pneumonia focused on measuring COVID-19 Pneumonia, Esophageal Pressure, Respiratory Drive

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

A.O.U. San Luigi Gonzaga Di OrbassanoRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm Type

Experimental

Arm Label

Spontaneous breathing, Venturi Mask FiO2 0.5, seated decubitus

Spontaneous breathing, Non Rebreathing Mask, seated decubitus

Continuous Positive Airway Pressure (CPAP) 7 cmH2O, FiO2 0.5, seated decubitus

Continuous Positive Airway Pressure (CPAP) 7 cmH2O, FiO2 0.5, supine decubitus

Continuous Positive Airway Pressure (CPAP) 7 cmH2O, FiO2 0.5, prone decubitus

Continuous Positive Airway Pressure (CPAP) 7 cmH2O, FiO2 1, seated decubitus

Continuous Positive Airway Pressure (CPAP) 12 cmH2O, FiO2 0.5, seated decubitus

Continuous Positive Airway Pressure (CPAP) 12 cmH2O, FiO2 1, seated decubitus

Arm Description

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.

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.

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.

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

Esophageal pressure swings at different levels of positive end-expiratory pressure (PEEP)

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)

Secondary Outcome Measures

Esophageal pressure swings at different levels of inspired oxygen fraction

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)

Esophageal pressure swings at different decubiti

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)

Full Information

NCT ID

NCT04885517

First Posted

May 11, 2021

Last Updated

May 12, 2021

Sponsor

San Luigi Gonzaga Hospital

1. Study Identification

Unique Protocol Identification Number

NCT04885517

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2021

Overall Recruitment Status

Unknown status

Study Start Date

February 1, 2021 (Actual)

Primary Completion Date

August 1, 2021 (Anticipated)

Study Completion Date

August 1, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

San Luigi Gonzaga Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

COVID-19 Pneumonia

Keywords

COVID-19 Pneumonia, Esophageal Pressure, Respiratory Drive

7. Study Design

Primary Purpose

Other

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

72 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Spontaneous breathing, Venturi Mask FiO2 0.5, seated decubitus

Arm Type

Experimental

Arm Description

Arm Title

Spontaneous breathing, Non Rebreathing Mask, seated decubitus

Arm Type

Experimental

Arm Description

Arm Title

Continuous Positive Airway Pressure (CPAP) 7 cmH2O, FiO2 0.5, seated decubitus

Arm Type

Experimental

Arm Description

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.

Arm Title

Continuous Positive Airway Pressure (CPAP) 7 cmH2O, FiO2 0.5, supine decubitus

Arm Type

Experimental

Arm Description

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.

Arm Title

Continuous Positive Airway Pressure (CPAP) 7 cmH2O, FiO2 0.5, prone decubitus

Arm Type

Experimental

Arm Description

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.

Arm Title

Continuous Positive Airway Pressure (CPAP) 7 cmH2O, FiO2 1, seated decubitus

Arm Type

Experimental

Arm Description

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.

Arm Title

Continuous Positive Airway Pressure (CPAP) 12 cmH2O, FiO2 0.5, seated decubitus

Arm Type

Experimental

Arm Description

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.

Arm Title

Continuous Positive Airway Pressure (CPAP) 12 cmH2O, FiO2 1, seated decubitus

Arm Type

Experimental

Arm Description

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.

Intervention Type

Device

Intervention Name(s)

Esophageal catheter

Intervention Description

Patients are equipped with an esophageal catheter: positioning is performed after accurate nasopharyngeal anesthesia with lidocaine

Primary Outcome Measure Information:

Title

Esophageal pressure swings at different levels of positive end-expiratory pressure (PEEP)

Description

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)

Time Frame

160 minutes

Secondary Outcome Measure Information:

Title

Esophageal pressure swings at different levels of inspired oxygen fraction

Description

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)

Time Frame

160 minutes

Title

Esophageal pressure swings at different decubiti

Description

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)

Time Frame

160 minutes

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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)

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Pietro Caironi, Pr

Phone

+390119026386

pietro.caironi@unito.it

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Pietro Caironi, MD

Organizational Affiliation

San Luigi Gonzaga Hospital

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Lorenzo Giosa, MD

Organizational Affiliation

San Luigi Gonzaga Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

A.O.U. San Luigi Gonzaga Di Orbassano

City

Orbassano

State/Province

Italy/Turin

ZIP/Postal Code

10043

Country

Italy

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Pietro Caironi, Pr

Phone

+390119026386

pietro.caironi@unito.it

12. IPD Sharing Statement

Plan to Share IPD

Citations:

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32228035

Citation

Gattinoni L, Coppola S, Cressoni M, Busana M, Rossi S, Chiumello D. COVID-19 Does Not Lead to a "Typical" Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med. 2020 May 15;201(10):1299-1300. doi: 10.1164/rccm.202003-0817LE. No abstract available.

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Citation

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

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