Clinical Evaluation of a Point of Care (POC) Assay to Identify Phenotypes in the Acute Respiratory Distress Syndrome

NCT ID: NCT04009330

Last Updated: 2025-07-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Total Enrollment

480 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-11-22

Study Completion Date

2026-02-27

Brief Summary

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Patients prospectively classified to the hyper-inflammatory ARDS phenotype on the basis of clinical characteristics and a novel POC biomarker assay will have worse clinical outcomes than the hypo-inflammatory phenotype.

Study Aim

The purpose of this project is to prospectively identify hyper- and hypo-inflammatory phenotypes in patients with ARDS and determine clinical outcomes associated with each phenotype.

The primary objective of this study is to assess the clinical outcomes in patients with ARDS according to their prospectively defined inflammatory phenotype determined using a POC assay.

Results of group allocation will be blinded to clinical and research staff until database lock.

Secondary Objectives

The secondary objectives of this study are to:

(i) Assess the agreement of the phenotype allocation using the POC assay and the clinical study dataset.

(ii) Assess the stability of phenotype allocation over time

(iii) To test feasibility of delivering a POC assay in the NHS intensive care setting.

Detailed Description

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Acute respiratory distress syndrome (ARDS) is an inflammatory condition that results in severe respiratory failure and the need for mechanical ventilation. It is a syndrome with significant global burden and accounts for approximately 24% of mechanically ventilated patients in intensive care units. It is estimated to account for approximately 75000 deaths annually in the USA alone.

Despite decades of research, mortality due to ARDS remains high at 35-46%, with increasing mortality in patients with more severe lung injury. ARDS survivors have significant long term comorbidity with reduced quality of life even 5 years after disease resolution. Various pharmacological agents such as β2 agonists, statins, keratinocyte growth factor and aspirin have been investigated as potential therapies to prevent or treat ARDS, however to date there is no effective pharmacological therapy for ARDS and current treatment strategy is largely supportive.

One reason for the lack of specific pharmacological therapy is likely due to the clinical and biological heterogeneity. It is essential to rapidly identify patients with specific therapy responsive traits to improve our chance of identifying a specific therapy.

Rationale for the Study

ARDS phenotypes have different outcomes and response to therapy.

The clinical and biological heterogeneity in ARDS makes it essential to identify homogenous phenotypes when investigating potential therapies.

A retrospective analysis of the clinical and biological data-set collected as part of two large multicentre studies (ARMA and ALVEOLI) using latent class analysis has identified at least two ARDS phenotypes. Furthermore these two phenotypes could be differentiated using a parsimonious data-set including the presence of shock, metabolic acidosis and a higher inflammatory status (IL-6 and sTNFr1). The hyper-inflammatory phenotype demonstrated significantly worse outcomes when compared to the hypo-inflammatory phenotype with higher mortality and less ventilator free and organ failure free days. In the ALVEOLI study, where low PEEP was compared to high PEEP strategy, the two phenotypes demonstrated a differential response to PEEP suggesting the potential for using this phenotypic classification in identifying a therapy responsive trait.

In addition, in a secondary analysis of the HARP-2 study, a multicentre study investigating the potential of simvastatin as an anti-inflammatory therapy for ARDS, the presence of a hyper- and hypo-inflammatory phenotype was confirmed. The hyper-inflammatory phenotype had a higher 28 day mortality, fewer ventilator free days and organ failure free days. Survival of patients classified as hyper-inflammatory and randomised to simvastatin was improved.

Implementation of a precision medicine approach to identify patients with a therapy response trait is crucial to identify specific therapies to prevent or treat ARDS. Development of a Point of Care (POC) assay for IL-6 and sTNFr1 for prospective confirmation of the inflammatory phenotypes using the parsimonious data-set in patients with ARDS will support a precision medicine approach for this condition.

A POC assay will support precision medicine for ARDS

Studies that show no benefit from an intervention could occur as a result of a variety of reasons including a) the intervention was ineffective, b) the study design was poor or c) patient heterogeneity. Reduction of patient heterogeneity to identify patients with common biological processes will enable the selection of patients with a higher likelihood of therapy response in clinical studies. The identification and institution of therapy for critically ill patients with ARDS needs to occur rapidly in view of the nature of the disease and development of an accurate POC assay is likely to be an essential component in the discovery of effective therapies.

Conditions

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Acute Respiratory Distress Syndrome (ARDS)

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Adults in the Intensive Care Setting

Adults in the Intensive Care Setting

POC Assay

Intervention Type DIAGNOSTIC_TEST

Interventions:

Blood Baseline - up to 40ml Day 3 - up to 40ml

Urine Baseline - 10ml Day 3 - 10ml

Study population:

Adults (18 plus) in ICU units diagnosed with ARDS.

Interventions

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POC Assay

Interventions:

Blood Baseline - up to 40ml Day 3 - up to 40ml

Urine Baseline - 10ml Day 3 - 10ml

Study population:

Adults (18 plus) in ICU units diagnosed with ARDS.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

1. Patient is receiving mechanical ventilation or high flow nasal oxygen (HFNO)
2. ARDS as defined by the Berlin definition (Ranieri et al.) a) Onset within 1 week of identified insult b) Within the same 24-hour time period: i. Hypoxic respiratory failure (PaO2/ FiO2 ratio ≤ 40kPa on PEEP ≥ 5 cmH20\*) ii. Bilateral infiltrates consistent with pulmonary oedema not explained by another pulmonary pathology iii. Respiratory failure not fully explained by cardiac failure or fluid overload

The time of onset of ARDS is when the last ARDS criterion is met.

\*PEEP assumed ≥ 5 cmH20 if on HFNO.

Exclusion Criteria

1. Age \<18 years of age
2. More than 48 hrs after onset of ARDS
3. Receiving ECMO at the time of recruitment
4. Treatment withdrawal imminent within 24 hours
5. DNAR (Do Not Attempt Resuscitation) order (excluding advance directives) in place
6. Declined consent
7. Prisoners
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Northern Ireland Clinical Trials Unit

OTHER

Sponsor Role collaborator

Innovate UK

OTHER_GOV

Sponsor Role collaborator

Queen's University, Belfast

OTHER

Sponsor Role lead

Responsible Party

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DannyMcAuley

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Professor D McAuley

Role: PRINCIPAL_INVESTIGATOR

Queens University Belfast

Locations

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St Vincents Hospital

Dublin, Ireland, Ireland

Site Status

University Hospital Birmingham

Birmingham, England, United Kingdom

Site Status

Royal Blackburn Hospital

Blackburn, England, United Kingdom

Site Status

Royal Liverpool University Hospital

Liverpool, England, United Kingdom

Site Status

University College London

London, England, United Kingdom

Site Status

Guys and St Thomas Hospital

London, England, United Kingdom

Site Status

Kings College Hospital

London, England, United Kingdom

Site Status

Wythenshawe Hospital

Manchester, England, United Kingdom

Site Status

Manchester Royal Infirmary

Manchester, England, United Kingdom

Site Status

Freemans Hospital

Newcastle upon Tyne, England, United Kingdom

Site Status

Nottingham University Hospital

Nottingham, England, United Kingdom

Site Status

Royal Berkshire Hospital

Reading, England, United Kingdom

Site Status

Sunderland Royal

Sunderland, England, United Kingdom

Site Status

Royal Cornwall Hospital

Truro, England, United Kingdom

Site Status

Edinburgh Royal Infirmary

Edinburgh, Scotland, United Kingdom

Site Status

Glasgow Royal Infirmary

Glasgow, Scotland, United Kingdom

Site Status

University Hospital of Wales

Cardiff, Wales, United Kingdom

Site Status

Royal Gwent Hospital

Newport, Wales, United Kingdom

Site Status

Royal Victoria Hospital

Belfast, , United Kingdom

Site Status

Birmingham Heartlands Hospital

Birmingham, , United Kingdom

Site Status

Imperial College London

London, , United Kingdom

Site Status

Oxford University Hospitals

Oxford, , United Kingdom

Site Status

Countries

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Ireland United Kingdom

References

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ARDS Definition Task Force; Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky AS. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012 Jun 20;307(23):2526-33. doi: 10.1001/jama.2012.5669.

Reference Type BACKGROUND
PMID: 22797452 (View on PubMed)

Other Identifiers

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B19/06

Identifier Type: -

Identifier Source: org_study_id

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