Clinical trial NCT04158492: Impact of Comprehensive Molecular Tests on Antimicrobial Stewardship in Community-acquired Pneumonia
Official title: Impact of Comprehensive Molecular Tests on Antimicrobial Stewardship in Community-acquired Pneumonia: an Open, Controlled and Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Community-acquired Pneumonia
Keywords: antimicrobial stewardship
point-of-care test
comprehensive molecular tests
multiple PCR
Lead sponsor: Hospital Universitari de Bellvitge
Sponsor class: OTHER
Collaborators: name: Fundació La Marató de TV3
name: Department of Health, Generalitat de Catalunya
First posted: 2019-11-08
Enrollment: 242
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Controlled, open-label clinical trial with two parallel groups (1:1) settled in two tertiary care hospitals
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of DOT
timeFrame: Up to 30±5 days after hospital discharge
Secondary outcomes:
measure: Number of days with intravenous antibiotic treatment.
timeFrame: Up to 30±5 days after hospital discharge
measure: Number of days until de-escalation
timeFrame: Up to 30±5 days after hospital discharge
measure: Number of days until antimicrobial monotherapy
timeFrame: Up to 30±5 days after hospital discharge
measure: Number of days until etiological diagnosis
timeFrame: Up to 30±5 days after hospital discharge
measure: Number of days of Oxygen treatment
timeFrame: Up to 30±5 days after hospital discharge
measure: Number of days of non-invasive ventilation
timeFrame: Up to 30±5 days after hospital discharge
measure: Number of days of hospital admission
timeFrame: Up to hospital discharge - a medium of 5 days
measure: Rate of readmissions
timeFrame: Up to 30±5 days after hospital discharge
measure: Rate of complicated community-acquired pneumonia (CAP)
timeFrame: Up to 30±5 days after hospital discharge
measure: Rate of general complications
timeFrame: Up to 30±5 days after hospital discharge
measure: Number of adverse events
timeFrame: Up to 30±5 days after hospital discharge
measure: Number of adverse events related to antimicrobials
timeFrame: Up to 30±5 days after hospital discharge
measure: Number of participants with Clostridium difficile infection
timeFrame: Up to 30±5 days after hospital discharge
measure: Phlebitis rate
timeFrame: Up to 30±5 days after hospital discharge
measure: Early mortality rate
timeFrame: Up tp 5 days after randomization
measure: 30 day case-fatality rate
timeFrame: Up to 30±5 days after randomization
measure: CAP-related fatality rate
timeFrame: Up to 30±5 days after hospital discharge
measure: All-cause fatality rate
timeFrame: Up to 30±5 days after hospital discharge
measure: Number of DOT per 1000 patients-day
timeFrame: Up to 30±5 days after hospital discharge
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol
state: Barcelona
city: Sant Joan Despí
country: Spain
facility: Moisés Broggi University Hospital
state: Barcelona
city: Barcelona
country: Spain
facility: SCIAS Hospital de Barcelona
state: Cataluña
city: Barcelona
country: Spain
facility: Hospital de Bellvitge
Study officials:
affiliation: Institut d'Investigació Biomèdica de Bellvitge
name: Jordi Carratalà Fernández, PhD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.