Clinical trial NCT01854424: Validation of the Percentage of Alveolar Fibrocyte as Biomarker During ARDS
Official title: Involvement of Fibrocytes in Repair Processes During Acute Respiratory Distress Syndrome (Validation Study-2)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Acute Respiratory Distress Syndrome (ARDS)
Mechanical Ventilation
Keywords: Fibrocyte
Acute Respiratory Distress Syndrome
Serum Amyloid P
Fibrosis
Mortality
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Institut National de la Santé Et de la Recherche Médicale, France
First posted: 2013-05-15
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Mechanically Ventilated patients after Sepsis, infectious pneumonia, trauma or postoperative complications.

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.

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.

Primary outcomes:
measure: To determine the percentage of alveolar fibrocytes in survivors vs. non survivors during ARDS
timeFrame: alveolar fibrocytes percentage in BALF obtained in the 48 hours following ARDS diagnosis
Secondary outcomes:
measure: To evaluate kinetics of alveolar and circulating fibrocytes between day-1 and day-14 of ARDS evolution
timeFrame: < day-2, day-3, day 5-7, day 10-14
measure: To test the prognostic value of the percentage of alveolar fibrocytes during ARDS
timeFrame: < day-2
measure: To evaluate the association between the percentage of alveolar fibrocyte and inflammatory and fibroproliferative markers
timeFrame: < day-2, day 5-7, day 10-14
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital TENON, département d'anesthésie-réanimation
Study officials:
affiliation: Assistance Publique
name: Christophe Quesnel, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: