A Molecular Toolkit for the Microbial Investigation of Severe Community Acquired Pneumonia (S-CAP)

A Molecular Toolkit for the Microbial Investigation of Severe Community Acquired Pneumonia (S-CAP Study)

Severe community acquired pneumonia is common and associated with high mortality. Conventional microbiological diagnostics identify pathogens in approximately half of cases, which is inadequate for both clinical and epidemiological purposes. This study applies next-generation sequencing based metagenomic techniques to patients with extremely severe community acquired pneumonia, to investigate the microbiome of severe community acquired pneumonia and evaluate metagenomic approaches as diagnostic tools.

Study Overview

• Status: Completed
• Conditions: Pneumonia; Community Acquired Pneumonia; Respiration Failure

• Study Type: Observational
• Enrollment (Actual): 103

Contacts and Locations

Study Locations

• United Kingdom
  • Paddington, United Kingdom, W2 1PG
    • Ajit Lalvani

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Adults admitted to Extra-Corporeal Membrane Oxygenation (ECMO) and Intensive Care Units (ICU) centres in England for severe community-acquired pneumonia

Description

Inclusion Criteria:

• Adults aged 18 or over
• Admitted to a participating severe respiratory failure centre or ICU
• Admitted due to community acquired pneumonia (CAP) according to clinical and radiological criteria
• Tracheal intubation, receiving mechanical ventilation +/- ECMO
• Requires bronchoscopy as part of routine diagnostic care plan
• Bronchoscopy takes place within 72 hours of first admission to hospital

Exclusion Criteria:

• Any current or previous condition/circumstance that, in the opinion of the investigator or study nurse, may put the individual at risk if participating
• Patients receiving end of life care
• Hospitalisation within the previous 28 days (not including pre-ECMO hospitalisation for ECMO patients)
• Consent or assent not given

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
SCAP requiring ECMO; Patients diagnosed with severe respiratory failure due to community acquired pneumonia that require extra-corporeal membrane oxygenation and a routine bronchoscopy for clinical purposes. Molecular laboratory techniques will be applied to residual respiratory tract samples including bronchoalveolar lavage and non-directed bronchoalveolar lavage. Comparisons will be made to conventional diagnostic tests used in the diagnosis of community acquired pneumonia.
SCAP requiring ITU support; Patients diagnosed with severe respiratory failure due to community acquired pneumonia that require intensive care support and undergo a routine bronchoscopy for clinical purposes. Molecular laboratory techniques will be applied to residual respiratory tract samples including bronchoalveolar lavage and non-directed bronchoalveolar lavage. Comparisons will be made to conventional diagnostic tests used in the diagnosis of community acquired pneumonia.
Healthy controls; Healthy volunteers who undergo bronchoscopy as part of a designated research bronchoscopy list. Molecular laboratory techniques will be applied to bronchoalveolar lavage samples.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Detection of pathogens by metagenomic sequencing applied to bronchoalveolar lavage samples	The proportion of pathogen genome that can be detected in bronchial lavage samples detected by the proportion of the sequenced nucleic acid which is pathogen derived and the proportion of the pathogen genome which be reconstructed.	28 days (From time of enrollment up until end of inclusion)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metagenomic detection of pathogen genomes compared to the results of conventional diagnostic techniques	Metagenomic sequencing data obtained will be compared to results obtained from conventional diagnostic tests undertaken as part of the participant's routine clinical care. Data will be used to evaluate the ability of each technique to detect any pathogens found. The conventional microbiological tests that will be used for comparison include those undertaken as part of the participants routine clinical care and will include urinary antigen tests (Pneumococcal and Leigonella); blood, sputum and bronchial lavage culture including polymerase chain reaction (PCR) for Legionella spp, Mycoplasma pneumoniae and Chlamydophila pneumoniae and respiratory viral PCR multiplex assays. The results of serological tests and PCR for Influenza A &B from nose and throat swabs will also be compared.	28 days (From time of enrollment up until end of inclusion)

Collaborators and Investigators

• Sponsor: Imperial College London
• Collaborators: NIHR HPRU in Respiratory Infections
• Investigators: Study Chair: Ajit Lalvani, MBBS,MRCP,FRCP, Imperial College London

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2016
• Primary Completion (Actual): October 1, 2018
• Study Completion (Actual): October 1, 2018

Study Registration Dates

• First Submitted: October 27, 2016
• First Submitted That Met QC Criteria: November 9, 2016
• First Posted (Estimate): November 15, 2016

Study Record Updates

• Last Update Posted (Actual): May 2, 2019
• Last Update Submitted That Met QC Criteria: May 1, 2019
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Diagnosis; Sequencing; Intensive care; Metagenome; Extra-corporeal membrane oxygenation (ECMO); Severe Respiratory Infections
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Respiratory Insufficiency; Pneumonia
• Other Study ID Numbers: SCAP2016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED