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

Sponsor

Imperial College London (Other)

Overall Status

Completed

CT.gov ID

NCT02963142

Collaborator

NIHR HPRU in Respiratory Infections (Other)

103

Enrollment

Location

Actual Duration (Months)

4.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Community Acquired Pneumonia Respiration Failure Pneumonia

Study Design

Study Type:

Observational

Actual Enrollment :

103 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Dec 1, 2016

Actual Primary Completion Date :

Oct 1, 2018

Actual Study Completion Date :

Oct 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
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.

Outcome Measures

Primary Outcome Measures

Detection of pathogens by metagenomic sequencing applied to bronchoalveolar lavage samples [28 days (From time of enrollment up until end of inclusion)]
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.

Secondary Outcome Measures

Metagenomic detection of pathogen genomes compared to the results of conventional diagnostic techniques [28 days (From time of enrollment up until end of inclusion)]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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