Acute Hypoxemic Respiratory FailureEARLY-SARDSNCT07281911
EARLY-SARDS: Early AlveolaR Lung biologY Underling Sepsis-Associated ARDS
An observational study of Acute Hypoxemic Respiratory Failure and Sepsis, run by Hospital Universitari Vall d'Hebron Research Institute at 1 site in Spain.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Hypoxemic Respiratory Failure, Sepsis, ARDS (Acute Respiratory Distress Syndrome)
- What is being tested?
- Serial bronchoalveolar lavage and biological-physiological assessment
- How many people
- 145 participants
- Where
- 1 siteSpain
- Study dates
- 15 Oct 2026to 1 Mar 2029
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Participants are adult ICU patients admitted with sepsis or septic shock who require invasive mechanical ventilation within 72 hours of sepsis diagnosis. These patients represent a high-risk population for sepsis-associated lung injury and ARDS, with dynamic biological and physiological changes occurring during the earliest phase of critical illness. The study follows participants for the first 96 hours after sepsis diagnosis to capture these early trajectories.
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Spain1 site
Hospital Universitari Vall d'Hebron
Barcelona, Barcelona, 08035
Maria Martínez Pla, MD, +34 636602073, maria.martinezpla@vallhebron.cat
About this study
Official title: 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
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.
Read the detailed description
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.
- Being tested
- Serial bronchoalveolar lavage and biological-physiological assessment
- Medical subject headings
- Respiratory Insufficiency, Sepsis, Acute Lung Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Serial bronchoalveolar lavage and biological-physiological assessmentDiagnostic test
At baseline (T0), blood samples and standardized respiratory physiological measurements, including gas exchange and ventilatory mechanics, will be obtained from all participants.
Bronchoalveolar lavage (BAL) will be performed only in invasively mechanically ventilated patients meeting predefined safety criteria.
T1 will occur 24 hours after T0 in patients already intubated or at the time of endotracheal intubation if this occurs within 72 hours of sepsis diagnosis.
T2 will be performed 96 hours after sepsis diagnosis and at least 24 hours after the previous assessment.
At each study point plasma sampling and physiological measurements will be repeated, while BAL will be repeated only when predefined safety criteria are fulfilled. All clinical management will remain at the discretion of the treating ICU team.
| Study group | Role | What they receive |
|---|---|---|
| Sepsis or Septic shock requiring mechanical ventilation | 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. Receives: Diagnostic Test: Serial bronchoalveolar lavage and biological-physiological assessment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Early lung injury trajectory within 96 hours of sepsis onset
Early lung injury trajectory, assessed as an ordinal composite endpoint integrating:
- occurrence of ARDS according to the Berlin Definition,
- time from sepsis diagnosis to ARDS onset,
- the highest Berlin ARDS severity stage (mild, moderate, or severe) reached during the 96-hour observation period.
This endpoint will serve as the outcome for development and internal validation of an integrated biological-physiological prediction model combining alveolar and systemic biomarkers with respiratory physiological variables.
Measured: Baseline to 96 hours
Secondary outcomes (3)
Alveolar-systemic biological compartmentalization
Alveolar-to-plasma biomarker gradients, concordance between paired bronchoalveolar lavage (BAL) and plasma biomarkers, and identification of compartmentalized biological profiles associated with early lung injury.
Measured: Baseline to 96 hours
Incremental predictive performance of integrated biological-physiological models
Improvement in model discrimination, calibration, reclassification, and clinical utility after incorporation of alveolar biomarkers and respiratory physiological variables into conventional clinical and plasma-based prediction models.
Measured: Baseline to 96 hours
Reproducibility and external validation of biological-physiological models
Assessment of biomarker distributions, alveolar-systemic gradients, biological-physiological subphenotype assignment, and prediction model performance across the prospective multicentre derivation cohort, including Vall d'Hebron and Uppsala University, with external validation in an independent retrospective Amsterdam UMC cohort.
Measured: Once study is completed, avarage 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2025
- Study start15 Oct 2026 (estimated)
- Primary completion1 Mar 2028 (estimated)
- Study completion1 Mar 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Acute Hypoxemic Respiratory FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 145 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospital Universitari Vall d'Hebron Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Amsterdam University Medical Centers (UMC), Location Academic Medical Center (AMC), Uppsala University Hospital, Fundació Parc Taulí
- Responsible party
- Sponsor
- Investigators
- Maria Martínez Pla, MD, Principal investigator, SODIR (Shock, Disfunció Orgànica i Ressuscitació)Luis Chiscano Camon, MD, PhD, Study director, SODIR (Shock, Disfunció Orgànica i Ressuscitació)Luis Morales Quinteros, MD, PhD, Study chair, SODIR (Shock, Disfunció Orgànica i Ressuscitació)Juan Carlos Ruiz Rodriguez, MD, PhD, Study director, SODIR (Shock, Disfunció Orgànica i Ressuscitació)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07281911
- Sponsor's protocol ID
- EARLY-SARDS-2025-11
- Acronym
- EARLY-SARDS
- Status last verified
- Aug 2026
- First submitted
- 2 Dec 2025
- Last updated
- 28 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: No plan to share IPD because of data sensitivity and institutional data protection requirements
Publications
Zhang S, Duitman J, Artigas A, Bos LDJ. The Complex Immune Cell Composition and Cellular Interaction in the Alveolar Compartment of Patients with Acute Respiratory Distress Syndrome. Am J Respir Cell Mol Biol. 2025 Mar;72(3):233-243. doi: 10.1165/rcmb.2024-0176TR.
PubMed 39383858Bos LD, Schouten LR, van Vught LA, Wiewel MA, Ong DSY, Cremer O, Artigas A, Martin-Loeches I, Hoogendijk AJ, van der Poll T, Horn J, Juffermans N, Calfee CS, Schultz MJ; MARS consortium. Identification and validation of distinct biological phenotypes in patients with acute respiratory distress syndrome by cluster analysis. Thorax. 2017 Oct;72(10):876-883. doi: 10.1136/thoraxjnl-2016-209719. Epub 2017 Apr 27.
PubMed 28450529Calfee CS, Delucchi K, Parsons PE, Thompson BT, Ware LB, Matthay MA; NHLBI ARDS Network. Subphenotypes in acute respiratory distress syndrome: latent class analysis of data from two randomised controlled trials. Lancet Respir Med. 2014 Aug;2(8):611-20. doi: 10.1016/S2213-2600(14)70097-9. Epub 2014 May 19.
PubMed 24853585Serpa Neto A, Deliberato RO, Johnson AEW, Bos LD, Amorim P, Pereira SM, Cazati DC, Cordioli RL, Correa TD, Pollard TJ, Schettino GPP, Timenetsky KT, Celi LA, Pelosi P, Gama de Abreu M, Schultz MJ; PROVE Network Investigators. Mechanical power of ventilation is associated with mortality in critically ill patients: an analysis of patients in two observational cohorts. Intensive Care Med. 2018 Nov;44(11):1914-1922. doi: 10.1007/s00134-018-5375-6. Epub 2018 Oct 5.
PubMed 30291378Calfee CS, Janz DR, Bernard GR, May AK, Kangelaris KN, Matthay MA, Ware LB. Distinct molecular phenotypes of direct vs indirect ARDS in single-center and multicenter studies. Chest. 2015 Jun;147(6):1539-1548. doi: 10.1378/chest.14-2454.
PubMed 26033126Auriemma CL, Zhuo H, Delucchi K, Deiss T, Liu T, Jauregui A, Ke S, Vessel K, Lippi M, Seeley E, Kangelaris KN, Gomez A, Hendrickson C, Liu KD, Matthay MA, Ware LB, Calfee CS. Acute respiratory distress syndrome-attributable mortality in critically ill patients with sepsis. Intensive Care Med. 2020 Jun;46(6):1222-1231. doi: 10.1007/s00134-020-06010-9. Epub 2020 Mar 23.
PubMed 32206845