Validation of the Percentage of Alveolar Fibrocyte as Biomarker During ARDS

Mechanical Ventilation Clinical Trial

— IFRA2  

Official title:

Involvement of Fibrocytes in Repair Processes During Acute Respiratory Distress Syndrome (Validation Study-2)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01854424
• Other study ID #: NI11026
• Secondary ID: AOM 11005
• Status: Completed
• Phase: N/A
• First received: May 13, 2013
• Last updated: March 21, 2017
• Start date: November 2013
• Est. completion date: July 11, 2016

Study information

• Verified date: March 2017
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 84
• Est. completion date: July 11, 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Lung Injury
• Acute Respiratory Distress Syndrome (ARDS)
• Mechanical Ventilation
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn
• Syndrome

Intervention

Other:
• 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.

Locations

Country	Name	City	State
France	Hôpital TENON, département d'anesthésie-réanimation	Paris

Sponsors (2)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	Institut National de la Santé Et de la Recherche Médicale, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the percentage of alveolar fibrocytes in survivors vs. non survivors during ARDS	Association with 28-day mortality after inclusion	alveolar fibrocytes percentage in BALF obtained in the 48 hours following ARDS diagnosis
Secondary	To evaluate kinetics of alveolar and circulating fibrocytes between day-1 and day-14 of ARDS evolution	number of fibrocytes in BALF and blood samples	< day-2, day-3, day 5-7, day 10-14
Secondary	To test the prognostic value of the percentage of alveolar fibrocytes during ARDS	Correlation between the percentage of alveolar or blood fibrocytes before day-2 and ventilation time (number of days without invasive ventilation between day 1 and day 28) and length of stay with organ failure (SOFA score evolution between day 1 and 28).	< day-2
Secondary	To evaluate the association between the percentage of alveolar fibrocyte and inflammatory and fibroproliferative markers	association between % of alveolar fibrocytes and markers of epithelial injury and fibroproliferation (alveolar and serum IL-8, IL-10, sRAGE, TGF-beta, procollagen III, SAP, CCL18, concentrations) evaluated at day 1, 3, 5-7 and 10-14.	< day-2, day 5-7, day 10-14