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

Overview

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.

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

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: December 2021

Interventions

  • 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
  • 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.

Arms, Groups and Cohorts

  • Active Comparator: Standard diagnostic tests
    • Patients who will undergo only the standard diagnostic procedures
  • 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).

Clinical Trial Outcome Measures

Primary Measures

  • DOT/1000 patients
    • Time Frame: Up to 30±5 days after hospital discharge
    • days of antibiotic therapy per 1000 patient-days

Secondary Measures

  • Intravenous antibiotic treatment.
    • Time Frame: Up to 30±5 days after hospital discharge
    • Days of intravenous antibiotic treatment
  • De-escalation
    • Time Frame: Up to 30±5 days after hospital discharge
    • Days until de-escalation of antibiotic treatment to another of narrower spectrum
  • Antimicrobial monotherapy
    • Time Frame: Up to 30±5 days after hospital discharge
    • Days until antibiotic monotherapy
  • Days till etiological diagnosis
    • Time Frame: Up to 30±5 days after hospital discharge
    • Days until detection of the causal agent
  • Oxygen treatment
    • Time Frame: Up to 30±5 days after hospital discharge
    • Days of oxygen treatment
  • Non-invasive ventilation
    • Time Frame: Up to 30±5 days after hospital discharge
    • Days of invasive or non-invasive mechanical ventilation
  • Days of hospital admission
    • Time Frame: Up to hospital discharge – a medium of 5 days
    • Days of hospital admission
  • Readmissions
    • Time Frame: Up to 30±5 days after hospital discharge
    • Patients who are readmitted after hospital discharge
  • Complicated community-acquired pneumonia (CAP)
    • Time Frame: Up to 30±5 days after hospital discharge
    • Complications related to CAP
  • General complications
    • Time Frame: Up to 30±5 days after hospital discharge
    • Patients with medical complications not directly related to CAP until the end of the clinical trial.
  • Adverse events
    • Time Frame: Up to 30±5 days after hospital discharge
    • Number of total adverse events.
  • Adverse events related to antimicrobials
    • Time Frame: Up to 30±5 days after hospital discharge
    • Number of adverse events related to antibiotic therapy.
  • Number of participants with Clostridium difficile infection
    • Time Frame: Up to 30±5 days after hospital discharge
    • Patients diagnosed with Clostridium difficile infection during the clinical trial.
  • Phlebitis rate
    • Time Frame: Up to 30±5 days after hospital discharge
    • Patients with phlebitis resulting from the use of intravenous drugs.
  • Early mortality
    • Time Frame: Up tp 5 days after randomization
    • Number of patients deceased 5 days after the randomization
  • 30 day case-fatality rate
    • Time Frame: Up to 30±5 days after randomization
    • Number of patients deceased 30±5 days after randomization
  • CAP-related fatality rate
    • Time Frame: Up to 30±5 days after hospital discharge
    • Number of patients Deceased patients, related to CAP during the clinical trial
  • All-cause fatality rate
    • Time Frame: Up to 30±5 days after hospital discharge
    • Patients who died from any cause during the clinical trial

Participating in This Clinical Trial

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

  • 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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Hospital Universitari de Bellvitge
  • Collaborator
    • Fundació La Marató de TV3
  • Provider of Information About this Clinical Study
    • Principal Investigator: Jordi Carratala, Head of Infectious Diseases – Hospital Universitari de Bellvitge

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