Pulmonary Fibrosis During Severe COVID-19 Pneumonia (FIBRO-COVID)

December 5, 2023 updated by: Hôpital Européen Marseille

Incidence, Risk Factors and Prognosis of Pulmonary Fibrosis During Severe COVID-19 Pneumonia

The COVID-19 pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), an emerging coronavirus, which has already infected 192 million people with a case fatality rate close to 2%. About 5% of patients infected with SARS CoV-2 have a critical form with organ failure. Among critical patients admitted to intensive care, about 70% of them will require ventilatory assistance by invasive mechanical ventilation (MV) with a mortality rate of 35% and a median MV duration of 12 days. The most severe lung damage resulting from SARS CoV-2 infection is the acute respiratory distress syndrome (ARDS). The virus infects alveolar epithelial cells and capillary endothelial cells leading to an activation of endothelium, hypercoagulability and thrombosis of pulmonary capillaries. This results in abnormal ventilation / perfusion ratios and profound hypoxemia. To date, the therapeutic management of severe SARS CoV-2 pneumonia lay on the early use of corticosteroids and Interleukin-6 (IL-6) receptor antagonist, which both reduce the need of MV and mortality. The risk factors of death in Intensive Care Unit (ICU) are: advanced age, severe obesity, coronary heart disease, active cancer, severe hypoxemia, and hepatic and renal failure on admission. Among MV patients, the death rate is doubled in those with both reduced thoracopulmonary compliance and elevated D-dimer levels. Patients with severe alveolar damage are at risk of progressing towards irreversible pulmonary fibrosis, the incidence of which still remain unknown. The diagnosis of pulmonary fibrosis is based on histology but there are some non-invasive alternative methods (serum or bronchoalveolar biomarkers, chest CT scan). We aim to assess the incidence of pulmonary fibrosis in patients with severe SARS CoV-2 related pneumonia. We will investigate the prognostic impact of fibrosis on mortality and the number of days alive free from MV at Day 90. Finally, we aim to identify risk factors of fibrosis.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Medical charts of patients admitted at the Intensive Care Unit (ICU) of the European Hospital of Marseille between March 2020 and June 2021 will be collected retrospectively using electronic database. Data collected will focus on demography, clinical variables, biological analyses, lung biopsies, and chest CT scans performed during the hospital stay.

Our routine protocol for COVID-19 management follows the "Coronavirus Disease 2019 (COVID-19) Treatment Guidelines" including the early use of corticosteroids (Dexamethasone) and IL-6 receptor antagonist (Tocilizumab). Additionally, we routinely perform, on a weekly basis, measurements of SARS CoV-2 viral load by PCR, SARS CoV-2 antibodies production, and biomarkers of fibrosis including hyaluronic acid (HA) and amino-terminal type I (PINP) and type III (PIIINP) peptides of procollagen.

The present study aim to determine the proportion of patients encountering non-invasive criteria of pulmonary fibrosis as defined by either typical CT scan patterns (reticulation and/or bronchiectasia), or increased serum concentration of PIIINP above 16 µg/L, or increased bronchoalveolar lavage (BAL) concentration of PIIINP above 9 µg/L.

A definitive diagnosis of lung fibrosis will be established according to lung pathology findings in patients for whom a lung biopsy have been performed during the hospital stay.

Patients with a diagnosis of pulmonary fibrosis will be compared with those without fibrosis, both in the population of mechanically ventilated patients and in those remained spontaneously breathing.

The primary end-point will be the number of days alive and free from the ventilator (ventilator-free days) at Day 90. The others outcomes of interest will be the duration of mechanical ventilation, the duration of ICU stay, the ICU mortality, the in-hospital mortality, the Day 28 mortality, and the Day 90 mortality.

The present study also aims to determine the risk factors of pulmonary fibrosis occurence, focusing on mechanical ventilatory settings, daily dose of corticosteroids, and the occurence of nosocomial pneumonia with special attention to lung reactivation of herpesviridae.

Finally, the relation between antibodies production and viral clearance (defined as the time to the first negative SARS CoV-2 PCR) or ICU survival will be investigated.

Study Type

Observational

Enrollment (Actual)

200

Contacts and Locations

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

Study Locations

  • France
      • Marseille, France, 13003
        • Hôpital Européen Marseille

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

N/A

Sampling Method

Non-Probability Sample

Study Population

The population will focused on patients with severe SARS Cov-2 pneumonia requiring ICU admission.

Description

Inclusion Criteria:

  • Acute hypoxemic respiratory failure
  • Positive SARS CoV-2 PCR on nasopharyngeal swab or distal airway sampling
  • ICU admission during the hospital stay

Exclusion Criteria:

  • Chronic respiratory failure (Oxygen or NIPPV at home)
  • Patients with "Do Not Resuscitate" order at ICU admission
  • Admission from an other ICU with a stay > 2 days
  • Transfer to an another ICU during the ICU stay

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

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Patients with pulmonary fibrosis

All ICU patients for which one of the non-invasive criteria of pulmonary fibrosis is reached :

  • Typical CT scan patterns (reticulation and/or bronchiectasia)
  • Serum PIIINP above 16 µg/L
  • BAL PIIINP above 9 µg/L
Diagnostic test: Aminoterminal type III peptide of procollagen
Serial Measurement of PIIINP in serum and/or BAL
Other Names:
  • PIIINP
Diagnostic test: Lung computed tomography
Screening for the presence of reticulation or bronchiectasia within lung parenchyma
Other Names:
  • Chest CT scan
Patients without pulmonary fibrosis
All ICU patients for which none of the non-invasive criteria of pulmonary fibrosis are reached.
Diagnostic test: Aminoterminal type III peptide of procollagen
Serial Measurement of PIIINP in serum and/or BAL
Other Names:
  • PIIINP
Diagnostic test: Lung computed tomography
Screening for the presence of reticulation or bronchiectasia within lung parenchyma
Other Names:
  • Chest CT scan

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ventilator-free days
Time Frame: Day 90
Number of days alive and free from mechanical ventilation
Day 90

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Day 90 mortality
Time Frame: Day 90
Mortality at Day 90
Day 90
Day 28 mortality
Time Frame: Day 28
Mortality at Day 28
Day 28
ICU Mortality
Time Frame: From date of ICU admission until the date of ICU liberation, assessed up to 6 months
Death from any cause during the ICU stay
From date of ICU admission until the date of ICU liberation, assessed up to 6 months
In-hospital Mortality
Time Frame: From date of hospital admission until the date of hospital liberation, assessed up to 12 months
Death from any cause during the Hospital stay
From date of hospital admission until the date of hospital liberation, assessed up to 12 months
Length of MV
Time Frame: From date of ICU admission until the date of ICU liberation, assessed up to 6 months
Duration of mechanical ventilation during the ICU stay
From date of ICU admission until the date of ICU liberation, assessed up to 6 months
Length of ICU stay
Time Frame: From date of ICU admission until the date of ICU liberation, assessed up to 6 months
Duration of ICU stay
From date of ICU admission until the date of ICU liberation, assessed up to 6 months
Length of hospital stay
Time Frame: From date of hospital admission until the date of hospital liberation, assessed up to 12 months
Duration of hospital stay
From date of hospital admission until the date of hospital liberation, assessed up to 12 months
Time to viral clearance
Time Frame: From date of first symptom until the date of ICU liberation, assessed up to 6 months
Time from first symptom to the first negative SARS CoV-2 PCR
From date of first symptom until the date of ICU liberation, assessed up to 6 months
Corticosteroid dose
Time Frame: From date of ICU admission until the date of ICU liberation, assessed up to 6 months
Daily corticosteroid dose (methylprednisolone equivalent)
From date of ICU admission until the date of ICU liberation, assessed up to 6 months
Lung herpesviridae reactivation
Time Frame: From date of ICU admission until the date of ICU liberation, assessed up to 6 months
Presence on BAL of at least one Herpesviridae (Cytomegalovirus, Epstein-Barr Virus, Herpes simplex virus, Human herpes virus-6)
From date of ICU admission until the date of ICU liberation, assessed up to 6 months
Blood herpesviridae reactivation
Time Frame: From date of ICU admission until the date of ICU liberation, assessed up to 6 months
Presence on serum of at least one Herpesviridae (Cytomegalovirus, Epstein-Barr Virus, Herpes simplex virus, Human herpes virus-6)
From date of ICU admission until the date of ICU liberation, assessed up to 6 months

Collaborators and Investigators

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

Sponsor

Hôpital Européen Marseille

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

Helpful Links

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)

March 11, 2020

Primary Completion (Actual)

June 30, 2021

Study Completion (Estimated)

December 31, 2025

Study Registration Dates

First Submitted

July 25, 2021

First Submitted That Met QC Criteria

July 29, 2021

First Posted (Actual)

August 3, 2021

Study Record Updates

Last Update Posted (Estimated)

December 6, 2023

Last Update Submitted That Met QC Criteria

December 5, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2021_06_02_JAS

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

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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