Impact of Comprehensive Molecular Tests on Antimicrobial Stewardship in Community-acquired Pneumonia

NCT04158492 | Terminated

• 1 other identifier: HUB-INF-RADICAP
• Study Type: interventional
• Target: 242
• Locations: 1 country
• Sites: 4

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.

Conditions

Community-acquired Pneumonia

Keywords

antimicrobial stewardship; point-of-care test; comprehensive molecular tests; multiple PCR

Outcome Measures

Primary Outcomes (1)

• Number of DOT

  Number of days of antibiotic therapy

  Up to 30±5 days after hospital discharge

Secondary Outcomes (19)

• Number of days with intravenous antibiotic treatment.

  Up to 30±5 days after hospital discharge

• Number of days until de-escalation

  Up to 30±5 days after hospital discharge

• Number of days until antimicrobial monotherapy

  Up to 30±5 days after hospital discharge

• Number of days until etiological diagnosis

  Up to 30±5 days after hospital discharge

• Number of days of Oxygen treatment

  Up to 30±5 days after hospital discharge

Study Arms (2)

Standard diagnostic tests

ACTIVE COMPARATOR

Patients who will undergo only the standard diagnostic procedures

Diagnostic Test: Standard diagnostic procedures

Experimental + standard diagnostic tests

EXPERIMENTAL

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

Interventions

real-time multiplex PCR DIAGNOSTIC_TEST

Patients will be randomly assigned to receive experimental diagnosis (comprehensive molecular testing added to routine microbiological testing) AND standard diagnosis microbiological procedures

Experimental + standard diagnostic tests

Standard diagnostic procedures DIAGNOSTIC_TEST

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.

Standard diagnostic tests

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Patient or his legal representative gives the informed consent

You may not qualify if:

• Patient with acute infection by SARS-CoV-2 being this defined as:
• Clinic of COVID-19 compatible, PCR positive for SARS-CoV-2 and negative serology for SARS-CoV-2.
• COVID-19 clinic compatible, PCR positive for SARS-CoV-2 (in the last 60 days) and positive serology for SARS-CoV-2.
• Pregnancy and / or nursing.
• 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).
• Imminent death (life expectancy ≤ 24 hours).
• Participation in another clinical trial of pharmacological treatment during the previous 3 months.

Sponsors & Collaborators

• Hospital Universitari de Bellvitge: lead
• Fundació La Marató de TV3: collaborator
• Department of Health, Generalitat de Catalunya: collaborator

Study Sites (4)

Hospital Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

Location

Moisés Broggi University Hospital

Sant Joan Despí, Barcelona, 08970, Spain

Location

SCIAS Hospital de Barcelona

Barcelona, Catalonia, 08022, Spain

Location

Hospital de Bellvitge

Barcelona, 08036, Spain

Location

Related Publications (3)

• Abelenda-Alonso G, Calatayud L, Rombauts A, Meije Y, Oriol I, Sopena N, Padulles A, Niubo J, Duarte A, Llaberia J, Aranda J, Gudiol C, Satorra P, Tebe C, Ardanuy C, Carratala J. Multiplex real-time PCR in non-invasive respiratory samples to reduce antibiotic use in community-acquired pneumonia: a randomised trial. Nat Commun. 2024 Aug 17;15(1):7098. doi: 10.1038/s41467-024-51547-8.

  PMID: 39154071 DERIVED

• Kerneis S, Visseaux B, Armand-Lefevre L, Timsit JF. Molecular diagnostic methods for pneumonia: how can they be applied in practice? Curr Opin Infect Dis. 2021 Apr 1;34(2):118-125. doi: 10.1097/QCO.0000000000000713.

  PMID: 33395094 DERIVED

• Abelenda-Alonso G, Rombauts A, Gudiol C, Meije Y, Clemente M, Ortega L, Ardanuy C, Niubo J, Padulles A, Videla S, Tebe C, Carratala J. Impact of comprehensive molecular testing to reduce antibiotic use in community-acquired pneumonia (RADICAP): a randomised, controlled, phase IV clinical trial protocol. BMJ Open. 2020 Aug 20;10(8):e038957. doi: 10.1136/bmjopen-2020-038957.

  PMID: 32819999 DERIVED

MeSH Terms

Conditions

Community-Acquired Pneumonia

Condition Hierarchy (Ancestors)

Community-Acquired Infections; Infections; Pneumonia; Respiratory Tract Infections; Respiratory Tract Diseases

Study Officials

• Jordi Carratalà Fernández, PhD

  Institut d'Investigació Biomèdica de Bellvitge

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Infectious Diseases

Model Details: Controlled, open-label clinical trial with two parallel groups (1:1) settled in two tertiary care hospitals

Study Record Dates

• First Submitted: October 28, 2019
• First Posted: November 8, 2019
• Study Start: February 20, 2020
• Primary Completion: April 24, 2023
• Study Completion: April 24, 2023
• Last Updated: April 28, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

ES (4)