Clinical trial NCT06282718: A Long-term Observational Study Evaluating the Presentation and Management of Acute Respiratory Tract Infections in Primary Care Across Europe
Official title: Perpetual Observational Study (POS) of Acute Respiratory Infections (ARI) in Primary Care Settings (PC) Across Europe
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Acute Respiratory Tract Infection
Lead sponsor: European Clinical Research Alliance for Infectious Diseases (ECRAID)
Sponsor class: OTHER
Collaborators: name: UMC Utrecht
name: University of Oxford
name: Universiteit Antwerpen
First posted: 2024-02-28
Enrollment: 2000
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients of any age group presenting to primary care settings with an ARI.

Brief summary: Acute respiratory infection (ARI) is the commonest reason for consulting in community care. Furthermore, new and re-emerging pathogens are often first noticed in primary care (PC). The POS-ARI-PC study is a long-term study, with the aim of describing the nature of ARI in adults and children presenting to PC across Europe. The POS-ARI-PC study will provide critically important data on the presentation and management of ARI, and build a research-ready infrastructure for studies related to the treatment, diagnosis, and prevention of ARI in primary care settings. Additional observational studies will be embedded and use the infrastructure developed in POS-ARI-PC.

Detailed description: The main aim for POS-ARI-PC is to provide a platform for continuous data capture for patients with ARI presenting to primary care settings across Europe, covering cases caused by known and emerging respiratory pathogens with epidemic and pandemic potential, in order to generate observational evidence to inform care and maintain study- readiness for RCT evaluations. The POS-ARI-PC platform will thereby support the efficient set-up of new clinical studies and trials, which will be embedded into the platform.

We have developed two overarching protocols for the POS-ARI-PC. The POS-ARI-PC AUDIT protocol allows for a flexible annual anonymous prospective audit-type registration to describe the presentation and management of patients presenting in primary care with ARI. This provides the infrastructure for patient sampling and follow-up, and in which randomisation can be activated for platform trials to evaluate a range of interventions that can be added and replaced over time. This has resulted in the POS-ARI-PC CORE protocol.

POS-ARI-PC AUDIT:

This is a flexible annual anonymous prospective audit-type registration to describe the presentation and management of patients presenting in primary care with ARI. POS-ARI-PC AUDIT will be delivered through a prospective, multi-country, audit-type anonymous registration of presentation and management of approximately 2,000 patients presenting to PC annually across Europe. This audit will benchmark the case mix and care of patients consulting in PC. These can include general practice, urgent care centres, accident and emergency and other acute services in hospitals, for adult and paediatric patients, both in and out of office hours.

POS-ARI-PC CORE:

This is a non-randomised, prospective, observational study of the presentation, management, microbiology and outcome of acute respiratory tract infection in primary care.

POS-ARI-PC CORE has the following three objectives:

Objective 1. A prospective, observational study of ARI patients in primary care to undergo study-specific sampling upon inclusion and be followed up for 28 days to capture the aetiology of their ARI and describe clinical outcomes.

Objective 2. A qualitative study with research professionals, clinicians, and patients to a) gain a deep understanding of the research process, and the meaning of results and to identify barriers and opportunities for implementation of changes considering findings, and b) explore the views and experiences of patients who consult European primary care services for ARI symptoms since the COVID-19 pandemic.

Objectives 3. To ensure research readiness for including embedded observational and randomised evaluations to answer questions about the effectiveness of diagnostic, behavioural or therapeutic management strategies for ARI in PC. When a new embedded observational study or RCT is added to the POS-ARI-PC a study-specific appendix (SSA) or an intervention-specific appendix (ISA) will be developed which details the (changes in) the study population, the research question, objectives, outcomes, study-specific processes and analysis. This will be appended to the POS-ARI-PC CORE Protocol and all appropriate approvals will be gained for each SSA or ISA.

Participation in the study will last for 28 days. Once consented to the study, a member of the study team will complete a short questionnaire collecting the participants' names and contact information, some details about them, and the symptoms they have been experiencing. A combined throat/nose swab will be collected from the patient for study purposes.

Participants will also be asked to tell us about how they are feeling today and for the next 14 days via an online or paper daily diary. They might be telephoned to ask some questions if they are unable to complete the daily diary. Their GP will be contacted after day 28 to collect information about their consultations and hospital referrals in the 28-day period.

A small number of enrolled participants who consented (optional) to be contacted by the research team about the nested qualitative study will be invited for a process evaluation interview.

POS-ARI-PC-001:

The first embedded study, POS-ARI-PC-001, will be conducted as a prospective observational study to estimate the incidence of medically-attended RSV, HMPV, HPIV and RV infections in an elderly population. This embedded study is appended to the POS-ARI-PC CORE Protocol as a study specific appendix (SSA).

Eligibility criteria: POS-ARI-PC AUDIT:

Inclusion Criteria:

Eligible patients will be of any age consulting (telephone, video, face-to-face) with a participating health care facility with:

* Symptoms suggestive of an acute lower RTI with cough as predominant symptom and with illness duration less than 28 days, AND/OR
* Symptoms suggestive of an acute upper RTI with sore throat and/or coryza as predominant symptom and with illness duration of less than 14 days AND/OR
* Patients otherwise suspected of COVID-19, influenza or RSV.

Exclusion Criteria:

Patients will not be eligible for if they have withdrawn their consent for anonymous data collection for research by their health care facility.

POS-ARI-PC CORE:

Inclusion criteria:

Eligible patients will be of any age consulting (telephone, video, face to face) with a participating primary health care facility with:

* Symptoms suggestive of an acute lower respiratory infection with cough as the predominant symptom, with illness duration less than 28 days, AND/OR
* Symptoms suggestive of an acute upper respiratory infection with sore throat and/or coryza as the predominant symptom, with illness duration of less than 14 days AND/OR
* Other symptoms suggestive of COVID-19, Influenza, RSV AND
* Participant or legal guardian(s) willing and able to provide informed consent and comply with study procedures

Exclusion criteria:

Patients will not be eligible if:

* According to the judgement of the recruiting clinician, they will not be able comply with study procedures, for example because they do not understand the language in which the study is being conducted locally (and have no one to help and translate for them); have a serious psychiatric disorder; or are terminally ill
* Symptoms of presumed non-infective origin
* Participant requires admission to hospital on the day of inclusion

Additional in/exclusion criteria might apply to embedded studies and will be described in the SSA or ISA.

POS-ARI-PC-001:

Symptoms and Duration Symptoms suggestive of an acute lower RTI with new or increased cough as the predominant symptom, with illness duration ≤10 days; AND/OR Symptoms suggestive of an acute upper RTI with sore throat and/or coryza as the predominant symptom, with illness duration ≤10 days;

Age Aged 60 years and over OR Aged 50 to 59 years and have a long-term health condition which makes them eligible for the yearly influenza vaccination under the national influenza vaccination programme;

Consent Willing and able to provide informed consent and have a swab taken.

Exclusion Criteria:

As per the POS-ARI-PC CORE Protocol, with one exception: patients needing hospitalisation can be recruited into the study if timing allows. Patients can provide a swab and decide not to participate in the follow-up procedures.

Primary outcomes:
measure: Age Bands
timeFrame: Baseline (Day 0)
measure: The proportion with a preliminary diagnosis of various sub-categories of ARI (e.g. LRTI, URTI)
timeFrame: Baseline (Day 0)
measure: Overall illness severity rating
timeFrame: Baseline (Day 0)
measure: Swab samples taken and retrospective viral/microbiological infection analysis performed (multiplex PCR) to identify potential causative pathogens.
timeFrame: Baseline (Day 0)
measure: Proportion undergoing POC (with results) and lab-based investigations
timeFrame: Baseline (Day 0) and day 28.
measure: Details of prescriptions given on presentation of ARI
timeFrame: Baseline (Day 0)
measure: Details of tests ordered on presentation of ARI
timeFrame: Baseline (Day 0)
measure: Return to usual daily activities
timeFrame: Day 1-14
measure: Feeling recovered from RTI
timeFrame: Day 1-14
measure: Use of prescription medication
timeFrame: Day 1-14
measure: Use of over the counter medications
timeFrame: Day 1-14
measure: Complications reported associated to ARI presentation
timeFrame: Day 28
measure: Variation in practice and advice from national guidelines, to be fed back to national teams
timeFrame: Baseline (Day 0)
Secondary outcomes:
measure: Recommendations on how to improve study processes, recruitment and study communication based on shared understanding and insights from researchers, clinicians, and patients.
timeFrame: After day 28
measure: An understanding of the meaning of study results for European primary care, from the perspectives of clinicians and patients, and recommendations regarding the implementation of findings.
timeFrame: After day 28
measure: An understanding of changing health-seeking behaviour, management and expectations to inform clinical studies and trials
timeFrame: After day 28
measure: Approval for a study-specific appendix (SSA) or an intervention-specific appendix (ISA) of an embedded (non) randomised study for ARI in primary care associated with this POS, measured using the number of embedded studies to this POS-ARI-PC platform over
timeFrame: Through study completion
Other outcomes:
Locations:
city: Antwerp
country: Belgium
facility: Universiteit Antwerpen
city: Limoges
country: France
facility: Centre Hospitalier Universitaire de Limoges
city: Oxford
country: United Kingdom
facility: University of Oxford
Study officials:
References: