Pulmonary Fibrosis During Severe COVID-19 Pneumonia

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

ACTIVE_NOT_RECRUITING

Total Enrollment

200 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-03-11

Study Completion Date

2025-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Severe Acute Respiratory Syndrome Coronavirus 2 Acute Respiratory Distress Syndrome Pulmonary Fibrosis

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

Mechanical Ventilation

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Observational Model Type

COHORT

Study Time Perspective

RETROSPECTIVE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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