RADICAP: Impact of Comprehensive Molecular Tests on Antimicrobial Stewardship in Community-acquired Pneumonia
Study Details
Study Description
Brief Summary
Background: Community-acquired pneumonia (CAP) continues to be a major health problem with significant mortality and it's one of the main causes of antibiotic prescription. Antibiotic overuse is a key driver of antimicrobial resistance and exposes patients to an increased risk of other antibiotic-related adverse events. The investigators aim to assess if rapid molecular tests are an effective tool to reduce antibiotic use in CAP compared to routine microbiological testing.
Design: Randomized, controlled, open-label clinical trial with two parallel groups (1:1) settled in a two-year multicenter, two tertiary care hospitals, between 2019 and 2021. Eligible participants will be non-severely immunosuppressed adult patients hospitalized for CAP through the emergency department. Primary endpoint will be antibiotic consumption measured by days of antibiotic therapy (DOT) per 1000 patient-days. Secondary end points will be: de-escalation to narrower antibiotic treatment, time to switch from intravenous to oral antibiotics, antibiotic-related side effects, length of hospital stay, days until clinical stability, need for ICU admission, need for hospital readmission in the 30 days after randomization, death from any cause in the 30 days after randomization. Patients will be randomly assigned to receive experimental diagnosis (comprehensive molecular testing added to routine microbiological testing) or standard diagnosis (only microbiological routine testing). A total of 220 patients are estimated in the experimental arm (undergoing comprehensive molecular testing) and 220 control subjects (undergoing routine testing) to be able to reject the null hypothesis that experimental and control groups have equal DOT per 1000 patients-days with a probability above 0.8.
Discussion: Comprehensive molecular tests could be a key tool in the optimization of etiological diagnostics in CAP and, therefore, a key element in antimicrobial stewardship programs developed to improve safety and antibiotic use in CAP.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Standard diagnostic tests Patients who will undergo only the standard diagnostic procedures |
Diagnostic Test: Standard diagnostic procedures
Patients who will undergo only the standard microbiological diagnostic procedures: blood cultures, Gram stain and culture sputum when possible, Gram and pleural fluid culture when appropriate, urine determination of the pneumococcal and Legionella pneumophila serogroup antigens type 1. A serological study will be carried out for the etiological agents of atypical pneumonia in the acute and convalescent phases of the infection.
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| Experimental: Experimental + standard diagnostic tests Patients will undergo described standard diagnostic procedures and in addition, real-time multiplex Protein Chain Reaction (PCR, FilmArray Pneumonia panel Plus ™, Biofire, BioMérieux). |
Diagnostic Test: real-time multiplex PCR
Patients will be randomly assigned to receive experimental diagnosis (comprehensive molecular testing added to routine microbiological testing) AND standard diagnosis microbiological procedures
|
Outcome Measures
Primary Outcome Measures
- Number of DOT/1000 patients [Up to 30±5 days after hospital discharge]
Number of days of antibiotic therapy per 1000 patient-days
Secondary Outcome Measures
- Number of days with intravenous antibiotic treatment. [Up to 30±5 days after hospital discharge]
Number of days of intravenous antibiotic treatment
- Number of days until de-escalation [Up to 30±5 days after hospital discharge]
Number of days until de-escalation of antibiotic treatment to another of narrower spectrum
- Number of days until antimicrobial monotherapy [Up to 30±5 days after hospital discharge]
Number of days untilt antimicrobial monotherapy
- Number of days until etiological diagnosis [Up to 30±5 days after hospital discharge]
Number of days until detection of the causal agent
- Number of days of Oxygen treatment [Up to 30±5 days after hospital discharge]
Days of oxygen treatment
- Number of days of non-invasive ventilation [Up to 30±5 days after hospital discharge]
Days of invasive or non-invasive mechanical ventilation
- Number of days of hospital admission [Up to hospital discharge - a medium of 5 days]
Number of days of hospital admission
- Rate of readmissions [Up to 30±5 days after hospital discharge]
Rate of patients who are readmitted after hospital discharge
- Rate of complicated community-acquired pneumonia (CAP) [Up to 30±5 days after hospital discharge]
Rate of complications related to CAP
- Rate of general complications [Up to 30±5 days after hospital discharge]
Patients with medical complications not directly related to CAP until the end of the clinical trial.
- Number of adverse events [Up to 30±5 days after hospital discharge]
Number of total adverse events.
- Number of adverse events related to antimicrobials [Up to 30±5 days after hospital discharge]
Number of adverse events related to antibiotic therapy.
- Number of participants with Clostridium difficile infection [Up to 30±5 days after hospital discharge]
Number of patients diagnosed with Clostridium difficile infection during the clinical trial.
- Phlebitis rate [Up to 30±5 days after hospital discharge]
Number of patients with phlebitis resulting from the use of intravenous drugs.
- Early mortality rate [Up tp 5 days after randomization]
Number of patients deceased 5 days after the randomization
- 30 day case-fatality rate [Up to 30±5 days after randomization]
Number of patients deceased 30±5 days after randomization
- CAP-related fatality rate [Up to 30±5 days after hospital discharge]
Number of patients Deceased patients, related to CAP during the clinical trial
- All-cause fatality rate [Up to 30±5 days after hospital discharge]
Number of patients who died from any cause during the clinical trial
Eligibility Criteria
Criteria
Inclusion Criteria:
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Adult patients (18 years of age or older), of both sexes, hospitalized with a diagnosis of CAP in the first 24 hours of the admission.
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Patient or his legal representative gives the informed consent
Exclusion Criteria:
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Patient with acute infection by SARS-CoV-2 being this defined as:
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Clinic of COVID-19 compatible, PCR positive for SARS-CoV-2 and negative serology for SARS-CoV-2.
OR
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COVID-19 clinic compatible, PCR positive for SARS-CoV-2 (in the last 60 days) and positive serology for SARS-CoV-2.
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Pregnancy and / or nursing.
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Severe immunocompromised patients (chemotherapy or radiotherapy in the previous 90 days, use of immunosuppressive drugs, chronic use of corticosteroids at a minimum dose of 15 mg / day in the last two weeks, transplantation of hematopoietic progenitors, solid organ transplant, patients with HIV and CD4 count ≤ 200 cells / mm3).
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Imminent death (life expectancy ≤ 24 hours).
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Participation in another clinical trial of pharmacological treatment during the previous 3 months.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hospital Germans Trias i Pujol | Badalona | Barcelona | Spain | 08916 |
| 2 | Moisés Broggi University Hospital | Sant Joan Despí | Barcelona | Spain | 08970 |
| 3 | SCIAS Hospital de Barcelona | Barcelona | Cataluña | Spain | 08022 |
| 4 | Hospital de Bellvitge | Barcelona | Spain | 08036 |
Sponsors and Collaborators
- Hospital Universitari de Bellvitge
- Fundació La Marató de TV3
- Department of Health, Generalitat de Catalunya
Investigators
- Study Director: Jordi Carratalà Fernández, PhD, Institut d'Investigació Biomèdica de Bellvitge
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- HUB-INF-RADICAP