Validation of the Percentage of Alveolar Fibrocyte as Biomarker During ARDS

NCT ID: NCT01854424

Last Updated: 2017-03-22

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 84 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2013-11-30
• Study Completion Date: 2016-07-11

Brief Summary

Fibrocyte is a monocyte sub-population involved in fibroproliferation/repair processes and associated with outcome in different diseases. In previous study, we have demonstrated the presence of alveolar fibrocytes during Acute expiratory Distress Syndrome (ARDS) and their association with patient outcome. The purpose of this multicentric observational prospective study is to describe the percentage of alveolar fibrocytes in ICU patients with ARDS (survivors vs. non survivors) and to confirm their association with 28-day mortality.

Detailed Description

Background: The acute respiratory distress syndrome (ARDS) remains common (15% of ventilated patients in the ICU), severe (30% of mortality) and have no specific treatment. Impaired epithelial repair with fibroproliferation is observed in non resolutive form of ARDS. Fibrocytes are cells that both express markers of hematopoietic cells (CD34+, CD45+) and fibroblasts (collagen-1). Fibrocytes may be recruited directly from the pool of circulating blood monocytes but also derive from monocytes in situ in absence of serum amyloid P (SAP or pentraxin-2). In murine models of lung injury, it has been shown that fibrocytes were recruited in the lung and contribute to the local fibrogenesis. Our team is the first to have demonstrated during ARDS in human the presence of fibrocytes among the alveolar cells obtained by bronchoalveolar lavage (BAL) (Quesnel et al, Eur Resp J, 2010). In a second single-center work enrolling 122 patients, we have shown that a percentage of alveolar fibrocytes > 6% was associated with an increased risk of death (HR = 6.2 [2.8 to 13.6], p <0.0001). However, this result remains to be confirmed in a second cohort because it was not the main objective of the first study and because of the variable lead time of BAL sampling in this cohort of patients with ARDS (Quesnel et al, CCM, 2012). Furthermore, the correlation of the percentage of blood fibrocytes (Fsg%) with the percentage of alveolar fibrocytes (Fal%) remains unknown and their kinetics remain to be studied during ARDS evolution.

Hypothesis and Objective: We hypothesize that percentage of alveolar fibrocytes is a prognostic marker during ARDS. Our main goal is to confirm in a validation cohort that the % of alveolar fibrocytes measured in BAL fluid during the first 48 hours of ARDS evolution is associated with 28-day mortality.

Conditions

Acute Respiratory Distress Syndrome (ARDS); Mechanical Ventilation

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Study Groups

ARDS

Ventilated patients with ARDS criteria (Berlin criteria) will be recruited in 3 ICU (2 from Bichat Hospital and 1 from Tenon Hospital, Paris) during the first 48 hours of their evolution. The patients will considered in 2 groups during analysis by taking into account their vital status at day-28 of inclusion.

Bronchoalveolar lavage (BAL) before day 2 , between days 5-7 and days 10-14 of evolution.

Intervention Type: OTHER

All the samples will be obtained during current care in the first week of evolution, and the last set of samples (BAL and blood sample between day 10-14) only in patients still under ventilation at this time point.

Interventions

Bronchoalveolar lavage (BAL) before day 2 , between days 5-7 and days 10-14 of evolution.

All the samples will be obtained during current care in the first week of evolution, and the last set of samples (BAL and blood sample between day 10-14) only in patients still under ventilation at this time point.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Ventilated patients with ARDS criteria as defined by Berlin criteria during the first 48 hours of evolution.

Exclusion Criteria

• refusal of patient participation, pregnancy, HIV infection, Respiratory insufficiency, Pulmonary fibrosis, cirrhosis (> Child B score), scleroderma, Alzheimer's disease, Bone marrow transplant, chemotherapy-induced aplasia, immunosuppressive therapy, Corticosteroids (> 200 mg/day of hydrocortisone or equivalent in the two weeks preceding inclusion), End of life patient or IGS2 greater than 90, brain death, therapeutic limitation.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institut National de la Santé Et de la Recherche Médicale, France

OTHER_GOV

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christophe Quesnel, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique

Locations

Hôpital TENON, département d'anesthésie-réanimation

Paris, , France

Countries

France

Other Identifiers

AOM 11005

Identifier Type: OTHER

Identifier Source: secondary_id

NI11026

Identifier Type: -

Identifier Source: org_study_id