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Active, Not Recruiting

NCT Number: NCT04987528

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Severe Acute Respiratory Syndrome Coronavirus 2 Acute Respiratory Distress Syndrome Fibrosis Lung Diseases Lung Diseases, Interstitial Pathologic Processes Pathological Conditions, Signs and Symptoms Pulmonary Fibrosis Respiration Disorders Respiratory Distress Syndrome Respiratory Tract Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Hopital Europeen Marseille

Marseille, 13003, France

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Aminoterminal type III peptide of procollagen

Diagnostic Test

Serial Measurement of PIIINP in serum and/or BAL

Other names: PIIINP

Lung computed tomography

Diagnostic Test

Screening for the presence of reticulation or bronchiectasia within lung parenchyma

Other names: Chest CT scan

Primary outcomes

  1. Ventilator-free days

    Time frame: Day 90

    Number of days alive and free from mechanical ventilation

Secondary outcomes

  1. Day 90 mortality

    Time frame: Day 90

    Mortality at Day 90

  2. Day 28 mortality

    Time frame: Day 28

    Mortality at Day 28

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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)

  10. 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)

  11. 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)

Sponsors and collaborators

Lead sponsor

Hôpital Européen Marseille

Other

Registry information

Official study title

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

Acronym: FIBRO-COVID

Important dates

Study start
2020
Primary completion
2027
Study completion
2027
First posted
Aug 3, 2021
Registry last updated
Jan 26, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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