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

Community-acquired Pneumonia Clinical Trial

— RADICAP  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04158492
• Other study ID #: HUB-INF-RADICAP
• Status: Terminated
• Phase: N/A
• Start date: February 20, 2020
• Est. completion date: April 24, 2023

Study information

• Verified date: April 2023
• Source: Hospital Universitari de Bellvitge
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 242
• Est. completion date: April 24, 2023
• Est. primary completion date: April 24, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Community-acquired Pneumonia
• Pneumonia

Intervention

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
• 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.

Locations

Country	Name	City	State
Spain	Hospital Germans Trias i Pujol	Badalona	Barcelona
Spain	Hospital de Bellvitge	Barcelona
Spain	SCIAS Hospital de Barcelona	Barcelona	Cataluña
Spain	Moisés Broggi University Hospital	Sant Joan Despí	Barcelona

Sponsors (3)

Lead Sponsor	Collaborator
Hospital Universitari de Bellvitge	Department of Health, Generalitat de Catalunya, Fundació La Marató de TV3

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of DOT	Number of days of antibiotic therapy	Up to 30±5 days after hospital discharge
Secondary	Number of days with intravenous antibiotic treatment.	Number of days of intravenous antibiotic treatment	Up to 30±5 days after hospital discharge
Secondary	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
Secondary	Number of days until antimicrobial monotherapy	Number of days untilt antimicrobial monotherapy	Up to 30±5 days after hospital discharge
Secondary	Number of days until etiological diagnosis	Number of days until detection of the causal agent	Up to 30±5 days after hospital discharge
Secondary	Number of days of Oxygen treatment	Days of oxygen treatment	Up to 30±5 days after hospital discharge
Secondary	Number of days of non-invasive ventilation	Days of invasive or non-invasive mechanical ventilation	Up to 30±5 days after hospital discharge
Secondary	Number of days of hospital admission	Number of days of hospital admission	Up to hospital discharge - a medium of 5 days
Secondary	Rate of readmissions	Rate of patients who are readmitted after hospital discharge	Up to 30±5 days after hospital discharge
Secondary	Rate of complicated community-acquired pneumonia (CAP)	Rate of complications related to CAP	Up to 30±5 days after hospital discharge
Secondary	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
Secondary	Number of adverse events	Number of total adverse events.	Up to 30±5 days after hospital discharge
Secondary	Number of adverse events related to antimicrobials	Number of adverse events related to antibiotic therapy.	Up to 30±5 days after hospital discharge
Secondary	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
Secondary	Phlebitis rate	Number of patients with phlebitis resulting from the use of intravenous drugs.	Up to 30±5 days after hospital discharge
Secondary	Early mortality rate	Number of patients deceased 5 days after the randomization	Up tp 5 days after randomization
Secondary	30 day case-fatality rate	Number of patients deceased 30±5 days after randomization	Up to 30±5 days after randomization
Secondary	CAP-related fatality rate	Number of patients Deceased patients, related to CAP during the clinical trial	Up to 30±5 days after hospital discharge
Secondary	All-cause fatality rate	Number of patients who died from any cause during the clinical trial	Up to 30±5 days after hospital discharge
Secondary	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