Pulmonary Fibrosis During Severe COVID-19 Pneumonia

NCT04987528 | Active Not Recruiting

• 1 other identifier: 2021_06_02_JAS
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

Keywords

Mechanical Ventilation

Outcome Measures

Primary Outcomes (1)

• Ventilator-free days

  Number of days alive and free from mechanical ventilation

  Day 90

Secondary Outcomes (11)

• Day 90 mortality

  Day 90

• Day 28 mortality

  Day 28

• ICU Mortality

  From date of ICU admission until the date of ICU liberation, assessed up to 6 months

• In-hospital Mortality

  From date of hospital admission until the date of hospital liberation, assessed up to 12 months

• Length of MV

  From date of ICU admission until the date of ICU liberation, assessed up to 6 months

Study Arms (2)

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; Diagnostic Test: Lung computed tomography

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; Diagnostic Test: Lung computed tomography

Interventions

Aminoterminal type III peptide of procollagen DIAGNOSTIC_TEST

Serial Measurement of PIIINP in serum and/or BAL

Also known as: PIIINP

Patients with pulmonary fibrosis; Patients without pulmonary fibrosis

Lung computed tomography DIAGNOSTIC_TEST

Screening for the presence of reticulation or bronchiectasia within lung parenchyma

Also known as: Chest CT scan

Patients with pulmonary fibrosis; Patients without pulmonary fibrosis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hôpital Européen Marseille: lead

Study Sites (1)

Hopital Europeen Marseille

Marseille, 13003, France

Location

Related Publications (5)

• Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC. Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review. JAMA. 2020 Aug 25;324(8):782-793. doi: 10.1001/jama.2020.12839.

  PMID: 32648899 BACKGROUND

• COVID-ICU Group on behalf of the REVA Network and the COVID-ICU Investigators. Clinical characteristics and day-90 outcomes of 4244 critically ill adults with COVID-19: a prospective cohort study. Intensive Care Med. 2021 Jan;47(1):60-73. doi: 10.1007/s00134-020-06294-x. Epub 2020 Oct 29.

  PMID: 33211135 BACKGROUND

• Grasselli G, Tonetti T, Protti A, Langer T, Girardis M, Bellani G, Laffey J, Carrafiello G, Carsana L, Rizzuto C, Zanella A, Scaravilli V, Pizzilli G, Grieco DL, Di Meglio L, de Pascale G, Lanza E, Monteduro F, Zompatori M, Filippini C, Locatelli F, Cecconi M, Fumagalli R, Nava S, Vincent JL, Antonelli M, Slutsky AS, Pesenti A, Ranieri VM; collaborators. Pathophysiology of COVID-19-associated acute respiratory distress syndrome: a multicentre prospective observational study. Lancet Respir Med. 2020 Dec;8(12):1201-1208. doi: 10.1016/S2213-2600(20)30370-2. Epub 2020 Aug 27.

  PMID: 32861276 BACKGROUND

• Forel JM, Guervilly C, Hraiech S, Voillet F, Thomas G, Somma C, Secq V, Farnarier C, Payan MJ, Donati SY, Perrin G, Trousse D, Dizier S, Chiche L, Baumstarck K, Roch A, Papazian L. Type III procollagen is a reliable marker of ARDS-associated lung fibroproliferation. Intensive Care Med. 2015 Jan;41(1):1-11. doi: 10.1007/s00134-014-3524-0. Epub 2014 Oct 30.

  PMID: 25354475 BACKGROUND

• Burnham EL, Hyzy RC, Paine R 3rd, Kelly AM, Quint LE, Lynch D, Curran-Everett D, Moss M, Standiford TJ. Detection of fibroproliferation by chest high-resolution CT scan in resolving ARDS. Chest. 2014 Nov;146(5):1196-1204. doi: 10.1378/chest.13-2708.

  PMID: 24722949 BACKGROUND

Related Links

• World Health Organization Coronavirus (COVID-19) Dashboard

MeSH Terms

Conditions

Respiratory Distress Syndrome; Pulmonary Fibrosis

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases, Interstitial; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2021
• First Posted: August 3, 2021
• Study Start: March 11, 2020
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: January 26, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)