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

Impact of Comprehensive Molecular Tests on Antimicrobial Stewardship in Community-acquired Pneumonia: an Open, Controlled and Randomized Clinical Trial

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.

Study Overview

• Status: Terminated
• Conditions: Community-acquired Pneumonia
• Intervention / Treatment: Diagnostic test: Standard diagnostic procedures; Diagnostic test: real-time multiplex PCR

• Study Type: Interventional
• Enrollment (Actual): 242
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jordi Carratalà Fernández, PhD; Phone Number: 5778 932607500; Email: jordicarratala@bellvitgehospital.com
• Study Contact Backup: Name: Gabriela Abelenda Alonso, PhD; Phone Number: 2075 932607500; Email: gabi.abelenda.alonso@gmail.com

Study Locations

• Spain
  • Barcelona, Spain, 08036
    • Hospital de Bellvitge
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Germans Trias i Pujol
    • Sant Joan Despí, Barcelona, Spain, 08970
      • Moisés Broggi University Hospital
  • Cataluña
    • Barcelona, Cataluña, Spain, 08022
      • SCIAS Hospital de Barcelona

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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.

OR

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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.
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of DOT	Number of days of antibiotic therapy	Up to 30±5 days after hospital discharge

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of days with intravenous antibiotic treatment.	Number of days of intravenous antibiotic treatment	Up to 30±5 days after hospital discharge
Number of days until de-escalation	Number of days until de-escalation of antibiotic treatment to another of narrower spectrum	Up to 30±5 days after hospital discharge
Number of days until antimicrobial monotherapy	Number of days untilt antimicrobial monotherapy	Up to 30±5 days after hospital discharge
Number of days until etiological diagnosis	Number of days until detection of the causal agent	Up to 30±5 days after hospital discharge
Number of days of Oxygen treatment	Days of oxygen treatment	Up to 30±5 days after hospital discharge
Number of days of non-invasive ventilation	Days of invasive or non-invasive mechanical ventilation	Up to 30±5 days after hospital discharge
Number of days of hospital admission	Number of days of hospital admission	Up to hospital discharge - a medium of 5 days
Rate of readmissions	Rate of patients who are readmitted after hospital discharge	Up to 30±5 days after hospital discharge
Rate of complicated community-acquired pneumonia (CAP)	Rate of complications related to CAP	Up to 30±5 days after hospital discharge
Rate of general complications	Patients with medical complications not directly related to CAP until the end of the clinical trial.	Up to 30±5 days after hospital discharge
Number of adverse events	Number of total adverse events.	Up to 30±5 days after hospital discharge
Number of adverse events related to antimicrobials	Number of adverse events related to antibiotic therapy.	Up to 30±5 days after hospital discharge
Number of participants with Clostridium difficile infection	Number of patients diagnosed with Clostridium difficile infection during the clinical trial.	Up to 30±5 days after hospital discharge
Phlebitis rate	Number of patients with phlebitis resulting from the use of intravenous drugs.	Up to 30±5 days after hospital discharge
Early mortality rate	Number of patients deceased 5 days after the randomization	Up tp 5 days after randomization
30 day case-fatality rate	Number of patients deceased 30±5 days after randomization	Up to 30±5 days after randomization
CAP-related fatality rate	Number of patients Deceased patients, related to CAP during the clinical trial	Up to 30±5 days after hospital discharge
All-cause fatality rate	Number of patients who died from any cause during the clinical trial	Up to 30±5 days after hospital discharge
Number of DOT per 1000 patients-day	Number of Days of antibiotic treatment per 1000 patients-day	Up to 30±5 days after hospital discharge

Collaborators and Investigators

• Sponsor: Hospital Universitari de Bellvitge
• Collaborators: Fundació La Marató de TV3; Department of Health, Generalitat de Catalunya
• Investigators: Study Director: Jordi Carratalà Fernández, PhD, Institut d'Investigació Biomèdica de Bellvitge

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2020
• Primary Completion (Actual): April 24, 2023
• Study Completion (Actual): April 24, 2023

Study Registration Dates

• First Submitted: October 28, 2019
• First Submitted That Met QC Criteria: November 7, 2019
• First Posted (Actual): November 8, 2019

Study Record Updates

• Last Update Posted (Actual): April 28, 2023
• Last Update Submitted That Met QC Criteria: April 26, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: antimicrobial stewardship; point-of-care test; comprehensive molecular tests; multiple PCR
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia
• Other Study ID Numbers: HUB-INF-RADICAP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data will be made available after evaluating individual request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No