Characterization of Early Biological and Mechanical Profiles in Sepsis-Associated ARDS for Studying Compartmentalization (Serial Bronchoalveolar Lavage and Plasma Biomarkers) to Identify Inflammatory and Hybrid Subphenotypes
| Registry | NCT07281911, acronym EARLY-SARDS |
|---|---|
| Status | Not yet recruiting |
| Study type | Observational |
| Enrollment | 145 (Estimated) |
| Sponsor | Hospital Universitari Vall d'Hebron Research Institute (Other); collaborators: Amsterdam University Medical Centers (UMC), Location Academic Medical Center (AMC), Uppsala University Hospital, Fundació Parc Taulí |
| Conditions | Acute Hypoxemic Respiratory Failure, Sepsis, ARDS (Acute Respiratory Distress Syndrome) |
| Interventions | Serial bronchoalveolar lavage and biological-physiological assessment (Diagnostic test) |
| Dates | start 2026-10-15 (estimated), primary completion 2028-03-01 (estimated), completion 2029-03-01 (estimated), first posted 2025-12-15, last updated 2026-08-28 |
| Locations | 1 site in Spain |
Related Papers Related Patents Related Grants Related Experts
All trials for Acute Hypoxemic Respiratory Failure All trials for Sepsis All trials of Serial bronchoalveolar lavage and biological-physiological assessment
Sepsis-associated acute respiratory distress syndrome (ARDS) remains a major cause of respiratory failure and mortality in critically ill patients. Although only a proportion of patients with sepsis develop ARDS, early identification of those at highest risk remains a major unmet clinical need. Current prediction relies largely on clinical deterioration and oxygenation impairment, which often occur when lung injury has already developed. Increasing evidence suggests that biological responses to sepsis are compartmentalized between the systemic circulation and the alveolar space, while early abnormalities in respiratory mechanics and ventilatory efficiency may provide complementary information on evolving lung injury. However, no prospective study has integrated serial systemic and alveolar biomarkers with bedside respiratory physiology during the earliest phase of sepsis-associated respiratory failure.
EARLY-SARDS is a prospective observational cohort study designed to characterize the early biological and physiological trajectories of invasively ventilated patients with sepsis or septic shock. Serial bronchoalveolar lavage (BAL) and plasma samples, together with standardized measurements of respiratory mechanics and gas exchange, will be collected during the first 96 hours after enrollment. The primary objective is to develop an integrated biological-physiological model capable of predicting ARDS development and subsequent peak ARDS severity. Secondary objectives include characterizing biological compartmentalization, identifying integrated biological-physiological subphenotypes, and evaluating their association with clinically relevant outcomes, including duration of mechanical ventilation, ventilator-free days, need for extracorporeal respiratory support, ICU length of stay, and mortality.
Acute respiratory distress syndrome (ARDS) secondary to sepsis is a biologically heterogeneous syndrome that reflects multiple interacting mechanisms of lung injury rather than a single pathological process. Current clinical definitions rely on physiological manifestations of established lung injury and therefore provide limited insight into the underlying biological processes responsible for disease initiation and progression.
Experimental and translational studies indicate that the earliest phase of sepsis-associated lung injury is characterized by dynamic interactions between inflammatory activation, epithelial injury, endothelial dysfunction, disruption of the alveolar-capillary barrier, and alterations in pulmonary permeability. These processes evolve rapidly during the first days after sepsis onset and may precede the clinical diagnosis of ARDS by several hours or days. Longitudinal characterization is therefore essential to understand the temporal evolution of lung injury.
Because the primary site of injury is the alveolar compartment, circulating biomarkers incompletely reflect the biological events occurring within the lung. Inflammatory mediators, epithelial injury markers, and endothelial activation frequently demonstrate compartmentalization between bronchoalveolar lavage (BAL) fluid and plasma, suggesting that simultaneous assessment of both compartments may provide a more comprehensive characterization of early lung injury than either compartment alone.
Respiratory physiology represents a complementary dimension of ARDS pathophysiology. Parameters including respiratory system compliance, driving pressure, plateau pressure, ventilatory ratio, and gas exchange describe the functional consequences of biological injury and the mechanical environment to which the lung is exposed during invasive mechanical ventilation. Mechanical stress and biological injury are closely interconnected and likely contribute jointly to disease progression.
By combining repeated assessment of alveolar biology, systemic host response, and respiratory physiology during the earliest phase of sepsis-associated respiratory failure, this study is designed to characterize the temporal evolution of lung injury and provide an integrated description of the biological and physiological mechanisms underlying progression to ARDS.
| Arm | Type | Interventions | Description |
|---|---|---|---|
| Sepsis or Septic shock requiring mechanical ventilation | Diagnostic Test: Serial bronchoalveolar lavage and biological-physiological assessment | Adult ICU patients with sepsis or septic shock requiring invasive mechanical ventilation within 72 hours from sepsis diagnosis will be consecutively enrolled and followed for 96 hours after sepsis diagnosis. |
Sex: All, ages: 18 Years to any
Inclusion Criteria * Age ≥18 years. * Sepsis or septic shock according to Sepsis-3 criteria. * Requirement for invasive mechanical ventilation within 72 hours of sepsis diagnosis. * Written informed consent provided by the participant or a legally authorized representative. Exclusion Criteria * Pregnancy. * Previous lung transplantation. * Contraindication to bronchoscopy or bronchoalveolar lavage (BAL).Inability to complete at least two BAL procedures during the 96-hour study period. * Expected death within 24 hours or limitation of life-sustaining treatment at enrollment. * Written informed consent not obtained.
| Facility | City | Country | Status |
|---|---|---|---|
| Hospital Universitari Vall d'Hebron | Barcelona, Barcelona | Spain |