Plain English Summary
Current plain English summary as of 06/08/2018:
Background and study aims
An acute respiratory infection (ARI) is a serious infection of the sinuses, throat, airways or lungs that prevents normal breathing function. Pathogens (viruses/bacteria) causing ARI are among the most likely candidates to cause the next pandemic. We need to better understand why some people become much more ill than others when they have an ARI. The elderly, people with chronic lung, heart or metabolic disease or immunocompromised (weakened immune system) patients are known to be at risk of developing severe disease. However, some respiratory infections can also cause severe disease in younger previously healthy individuals due to a combination of the virus itself and the individual’s immune responses. It is likely that individual risk factors affect the body’s response to ARI in different ways and this in turn can influence the severity of disease. Within broad risk groups it is currently not possible to predict which individuals are at increased risk of becoming severely ill. Consequently, there are no opportunities to tailor treatments. In people who become moderately or severely ill, there is an assumption that the body’s underlying response to disease is the same and hence that everyone will benefit equally from the same treatments. Increased insight into how different individuals respond to respiratory pathogens can allow us to better anticipate the severity of disease for a particular patient. This in turn will enable us to make strategies for individualized treatment options to reduce disease severity, risk of complications and hospitalisations.
Who can participate?
People aged over 18 attending primary and secondary care with mild to severe ARI.
What does the study involve?
Blood and respiratory (lung) samples will be collected from patients. We will analyse the samples to observe individual gene activity and we will compare samples from people with different risk factors for more severe disease. This will provide a detailed insight into how the body responds to infection and provide opportunities to understand the specific contributions of different risk factors.
What are the possible benefits and risks of participating?
There will be no direct benefit to participants. The study includes serial biological sampling which is in addition to that required for medical management. The results of the tests done on these samples may not contribute to improving the participant’s health. The results of this study will not be available in time to contribute to the patient’s care for this episode of ARI. This is an observational study and thus it is a very low-risk study. Participants will have three blood draws, which can be associated with pain at the draw site and rarely with infection. Respiratory swabs may be uncomfortable to obtain. Discomfort and risk will be minimized by using experienced clinical staff at each site. Participation in this research study poses a minimal risk of inconvenience through attendance of two follow-up visits. The risks are even lower for secondary care participants as the research sampling will be timed to coincide with routine clinical sampling which normally occurs daily in acutely unwell patients in hospital.
Where is the study run from?
Tropical Medicine, University of Oxford (UK)
When is the study starting and how long is it expected to run for?
October 2015 to June 2019
Who is funding the study?
European Commission (Belgium)
Who is the main contact?
James Lee
james.lee@ndm.ox.ac.uk
Previous plain English summary:
Background and study aims
An acute respiratory infection (ARI) is a serious infection of the sinuses, throat, airways or lungs that prevents normal breathing function. Pathogens (viruses/bacteria) causing ARI are among the most likely candidates to cause the next pandemic. We need to better understand why some people become much more ill than others when they have an ARI. The elderly, people with chronic lung, heart or metabolic disease or immunocompromised (weakened immune system) patients are known to be at risk of developing severe disease. However, some respiratory infections can also cause severe disease in younger previously healthy individuals due to a combination of the virus itself and the individual’s immune responses. It is likely that individual risk factors affect the body’s response to ARI in different ways and this in turn can influence the severity of disease. Within broad risk groups it is currently not possible to predict which individuals are at increased risk of becoming severely ill. Consequently, there are no opportunities to tailor treatments. In people who become moderately or severely ill, there is an assumption that the body’s underlying response to disease is the same and hence that everyone will benefit equally from the same treatments. Increased insight into how different individuals respond to respiratory pathogens can allow us to better anticipate the severity of disease for a particular patient. This in turn will enable us to make strategies for individualized treatment options to reduce disease severity, risk of complications and hospitalisations.
Who can participate?
People aged over 18 attending primary and secondary care with mild to severe ARI.
What does the study involve?
Blood and respiratory (lung) samples will be collected from patients. We will analyse the samples to observe individual gene activity and we will compare samples from people with different risk factors for more severe disease. This will provide a detailed insight into how the body responds to infection and provide opportunities to understand the specific contributions of different risk factors.
What are the possible benefits and risks of participating?
There will be no direct benefit to participants. The study includes serial biological sampling which is in addition to that required for medical management. The results of the tests done on these samples may not contribute to improving the participant’s health. The results of this study will not be available in time to contribute to the patient’s care for this episode of ARI. This is an observational study and thus it is a very low-risk study. Participants will have three blood draws, which can be associated with pain at the draw site and rarely with infection. Respiratory swabs may be uncomfortable to obtain. Discomfort and risk will be minimized by using experienced clinical staff at each site. Participation in this research study poses a minimal risk of inconvenience through attendance of two follow-up visits. The risks are even lower for secondary care participants as the research sampling will be timed to coincide with routine clinical sampling which normally occurs daily in acutely unwell patients in hospital.
Where is the study run from?
Oxfordshire Primary Care Trust (UK).
When is the study starting and how long is it expected to run for?
From October 2015 to May 2018.
Who is funding the study?
European Commission.
Who is the main contact?
Emmanuelle Denis
Trial website
Contact information
Type
Public
Primary contact
Mr James Lee
ORCID ID
Contact details
Wellcome Trust Centre for Human Genetics
University of Oxford
Roosevelt Drive
Oxford
OX3 7BN
United Kingdom
+44 (0) 1865 612979
james.lee@ndm.ox.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
Scientific title
Multi-centre EuRopean study of MAjor Infectious Disease Syndromes (MERMAIDS) – Observational Study of Acute Respiratory Infections in Primary and Secondary Care
Acronym
MERMAIDS-ARI
Study hypothesis
In this study we will recruit people attending primary and secondary care in order to capture people with mild to severe acute respiratory infections (ARI). We will analyse samples to observe individual gene activity and we will compare samples from people with different risk factors for more severe disease. This will provide a detailed insight into how the body responds to infection and provide opportunities to understand the specific contributions of different risk factors.
Ethics approval
NRES Committee West Midlands - The Black Country, 27/08/2015, ref: 15/WM/0254
Study design
Multi-centre observational study
Primary study design
Observational
Secondary study design
Case series
Trial setting
Hospitals
Trial type
Other
Patient information sheet
Condition
Acute respiratory infections
Intervention
This is an observational study. Blood and respiratory samples will be collected at baseline, day 2, date of hospital discharge (if applicable) and day 28. Samples will be analysed to determine aetiology of respiratory infection and to identify host and pathogen related determinants of severity of infection.
Intervention type
Other
Phase
Drug names
Primary outcome measure
Differentially expressed host genes (nominal ≥ 2-fold difference in expression levels) as assessed by RNA transcriptome microarray in hospitalised and primary care managed cases of ARI, stratified by pathogen* and comorbidity**.
*Influenza virus, Human Rhinovirus, Respiratory Syncytial Virus, Streptococcus pneumoniae
**No comorbidity, chronic pulmonary disease, chronic cardiovascular disease, chronic metabolic disease (diabetes)
Secondary outcome measures
In both groups:
1. Prevalence of detection of putative pathogens in respiratory tract samples
2. Proportion of cases receiving antibiotics, antivirals, antifungals and/or immunomodulators.
3. 28-day mortality
Additional in group 1 (primary care):
1. Proportion of cases requiring hospitalisation
Additional in group 2 (hospitalised patients):
1. Severity of illness at enrolment as assessed by Pneumonia Severity Index (PSI) and CURB-65
2. Proportion of cases requiring during admission: supplemental oxygen; non-invasive or invasive mechanical ventilation; extra-corporeal life support
3. Duration of invasive mechanical ventilation and extra-corporeal life support, if applicable
4. Proportion of cases requiring Intensive Care Unit (ICU)/High Care Unit (HCU) admission
5. Hospital and ICU/HCU length of stay
6. In-hospital mortality
Overall trial start date
01/10/2015
Overall trial end date
18/06/2019
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Group 1 – primary care patients:
1. Age ≥ 18 years
2. Patient is self-attending to primary care (i.e. ambulatory)
3. Clinical suspicion of a new episode of acute respiratory tract infection
4. Onset of the following symptoms within the last 7 days:
4.1. Sudden onset of self-reported fever OR tympanic temperature of ≥ 38°C at presentation
AND
4.2. At least one respiratory symptom (cough, sore throat, runny or congested nose)
AND
4.3. At least one systemic symptom (headache, muscle ache, sweats or chills or tiredness)
Group 2 – hospitalised patients:
1. Age ≥ 18 years
2. Clinical suspicion of a new episode of acute respiratory tract infection
3. Patient is admitted to hospital
4. Primary reason for hospital admission is clinical suspicion of a new episode of ARI
5. Onset of the following symptoms within the last 7 days:
5.1. Sudden onset of self-reported fever OR tympanic temperature of ≥ 38°C at presentation
AND
5.2. At least one respiratory symptom (cough, sore throat, runny or congested nose)
AND
5.3. At least one systemic symptom (headache, muscle ache, sweats or chills or tiredness)
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
2000
Participant exclusion criteria
Group 1 – primary care patients:
1. Patient lacks capacity to provide informed consent
2. No informed consent is provided by patient
3. The attending primary care physician decided to send patient to the hospital for assessment and possible hospital admission
4. Patient is enrolled in an interventional clinical study
Group 2 – hospitalised patients:
1. Patient lacks capacity to provide informed consent
2. No informed consent is provided by patient
3. Patient has been transferred from another hospital
4. Patient is enrolled in an interventional clinical study
Recruitment start date
01/10/2015
Recruitment end date
30/04/2019
Locations
Countries of recruitment
Croatia, Germany, Ireland, Netherlands, Poland, Romania, Spain, United Kingdom
Trial participating centre
Oxfordshire Primary Care Trust
OX4 2LH
United Kingdom
Sponsor information
Organisation
University of Oxford (UK)
Sponsor details
Joint Research Office
Block 60
Churchill Hospital
Oxford
OX3 7LE
United Kingdom
Sponsor type
University/education
Website
Funders
Funder type
Government
Funder name
European Commission
Alternative name(s)
EC
Funding Body Type
government organisation
Funding Body Subtype
Federal/National Government
Location
Results and Publications
Publication and dissemination plan
To be confirmed at a later date
Intention to publish date
Participant level data
Stored in repository
Basic results (scientific)
Publication list