Work Package 4

Objectives

To further develop, coordinate and manage a sustainable European Standardised Care Network (ESCAN) with broad European coverage providing access to a large population suffering from CA-ARTI across all age groups and different community care settings, differing antimicrobial stewardship programs, country level income and differing levels of outpatient antibiotic use.
To generate clinical evidence about current care and the potential value of clinical algorithms that include one or more CA-ARTI-Dx by benchmarking current clinical practice for CA-ARTI in 20 EU Member states and H2020 Associated Countries selected from our existing COMBACTE, PREPARE, PENTA-ID and LOTTA-Net networks and enhanced with further networks, on the basis of levels of income, variation in antibiotic stewardship programs, and levels of antibiotic prescribing.
To design and implement a novel, robust, flexible and efficient randomised controlled trial of the clinical and cost-effectiveness of algorithms including one or more CA-ARTI-Dx for managing CA-ARTI in community care in 10 EU Member States and H2020 Associated Countries (selected on the basis of the results of the point prevalence audit survey; PPAS).

Because of critical differences in setting and logistics, it was decided to separate the primary care/long term care facilities and hospital based clinical studies in WP4 into separate studies and protocols, now labelled the PRUDENCE and ADEQUATE trials respectively.

PRUDENCE

Platform Randomised controlled trial of point of care Diagnostics for Enhancing the quality of aNtibiotic prescribing for Community acquired acute respiratory tract infection (CA-ARTI) in ambulatory care in Europe

What is PRUDENCE?

The invention of antimicrobials was a major breakthrough in medical science. Antimicrobials are used to treat illness caused by bacteria. Development of these medicines meant that illnesses, like pneumonia, which were once often fatal, could now usually be successfully treated. That saved millions of lives. But effectiveness of antimicrobials is now decreasing because they are being overused. Microorganisms that are being exposed to antimicrobials change genetically over time, making it harder for the antimicrobials to work against them. As a result, “superbugs” are developing. We have no effective treatment for some of these “superbugs”. The development of resistance to antimicrobials is a major public health concern worldwide. Unhelpful, clinically unwarranted variation in care is a major contributor. Point-of-care testing that is proven to be cost-effective in clinical trials could help improve the quality of care and thus patient outcomes. This is especially true for community-acquired acute respiratory tract infections (CA-ARTI), the most common acute reasons for consulting health services in community care setting and for antimicrobial use.

The aim of PRUDENCE is to determine if having a CA-ARTI diagnostic (CA-ARTI-Dx) test result available when a clinician is considering, or plans to prescribe an antimicrobial, leads to more appropriate prescribing decisions, without causing harm to patients. PRUDENCE is a multi-country, prospective, individually randomised, platform clinical trial in community care with a nested process evaluation. The trial is a diagnostic strategy intervention study to evaluate the use of clinical algorithms that include a CA-ARTI-Dx, compared to usual clinical care without CA-ARTI-Dx.

PRUDENCE objectives

Primary objectives:
To assess effectiveness of CA-ARTI-Dx in terms of both reductions in antimicrobial prescribing, and in terms of patient recovery.

Secondary objectives:
To explore whether adding a CA-ARTI-DX to usual primary care:

Additional effects on antimicrobial prescribing
Effects antimicrobial use
Effects patient recovery and safety, including complications and hospitalisation
Effects use of medications other than antimicrobials
Effects clinician’s decision making process regarding diagnosis and treatment
Effects patients’ perceived ability to understand and cope with their illness
Is cost effective

To identify:

Clinicians’ views and experiences of CA-ARTI-Dx and how they fit with/impact on delivery of care and intended future use
Patient/parent views of CA-ARTI-Dx and how they impact consultations including patient satisfaction and intention to consult in future for similar symptoms

ADEQUATE

Advanced Diagnostics for Enhanced QUality of Antibiotic prescription in respiratory Tract infections in Emergency rooms

What is ADEQUATE?

Community-acquired acute respiratory tract infections (CA-ARTI) are among the most frequent infectious diseases worldwide. Uncomplicated ARTI is the most frequent cause of inappropriate antibiotic use, and there is a need of more judicious antibiotic prescribing to prevent exposure to drug-related adverse events, selection of antibiotic resistance and emergence of opportunistic pathogens that substitute the indigenous microbiota. Antibiotic resistance rates are related to antibiotic use in any setting, but opportunities to decrease unnecessary treatments are probably most apparent in primary care and emergency departments.

Optimal clinical management of CA-ARTI is hampered because of diagnostic delays and suboptimal test sensitivity, leading to incorrect or missing etiologic diagnosis, and overprescription of antibiotics.

There is a need to assess the impact of rapid syndromic diagnostic testing in patients with CA-ARTI presenting to Emergency Rooms on clinical decision making related to hospitalization and antibiotics prescribing. At the same time it must be determined whether the decisions guided by the rapid syndromic diagnostic testing results do not compromise patient safety.

ADEQUATE is a randomized controlled trial of Rapid Syndromic Diagnostic testing for enhancing the quality of antibiotic prescribing for community acquired acute respiratory tract infection (CA-ARTI) in Emergency Rooms in Europe.

ADEQUATE objectives

Primary objectives:

To assess the impact of rapid syndromic diagnostic testing in patients with CA-ARTI in ER on:

days in hospital within 14 days after study enrolment
days with antibiotic therapy within 14 days after study enrolment
occurrence of adverse outcome within 30 days after study enrolment

Secondary objectives:

To collect health care utilization and quality of life data for health economical modelling and to determine long-term clinical, public health, economic and societal impact of diagnostics in terms of antimicrobial resistance prevention
To quantify the additional diagnostic yield of rapid syndromic diagnostic testing (e.g. atypical pathogens, virus)
To quantify the impact of rapid syndromic diagnostic testing on antimicrobial de-escalation and the choice of antibiotics
To estimate the integral value of diagnostics related to existing diagnostic and antimicrobial stewardship programs at local level

Exploratory Objectives

To biobank well characterized clinical samples to encompass objectives from WP2. This will be limited to samples obtained from children
Collect comprehensive data on clinical status and laboratory results for validation of clinical algorithms developed in WP1
To assess the impact of rapid syndromic diagnostic testing on patient bed management/isolation measures
To describe the current policy environment in Europe and identify good practices and widen the existing networks for assessments of innovative diagnostics