Clinical trial NCT05841875: Efficacy and Safety of a Protocol Using C-reactive Protein to Guide Antibiotic Therapy
Official title: Efficacy and Safety of a Protocol Using C-reactive Protein to Guide Antibiotic Therapy Applied Through a Digital Clinical Decision Support Tool: a Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Systemic Infection
Keywords: Systemic infection
Sepsis
Biomarkers
C reactive protein
Antibiotic
Antibiotic stewardship
Lead sponsor: Federal University of Minas Gerais
Sponsor class: OTHER
Collaborators: name: Conselho Nacional de Desenvolvimento Científico e Tecnológico
name: FAPEMIG - FundaÃ§Ã£o de Amparo a Pesquisa do Estado de Minas Gerais
First posted: 2023-05-03
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel Assignment
Primary purpose: TREATMENT

Brief summary: The growing resistance of microorganisms to antimicrobials is a major threat to public health nowadays. Reducing the consumption of antibiotics is one of the main strategies to control this issue. Protocols using biomarkers to guide antimicrobial therapy have been studied, with promising results in safely reducing patient exposure to these drugs by reducing duration of treatments. Procalcitonin (PCT) and C-reactive protein (CRP) represent the most promising biomarkers in this context. Although less studied, CRP has the potential advantages of lower cost and wide availability when compared to PCT. However, decision algorithms involving biomarkers proposed in studies published so far are very far from daily medical practice in hospitals, mainly because there is poor accessibility to these protocols, and because most of them do not contemplate each patients clinical variables. The objective of this project is to evaluate the efficacy and safety of a multimodal protocol using clinical variables and the CRP value to guide antibiotic therapy in hospitalized patients. This protocol will be applied diretcly by the assistant medical teams through a digital clinical decision support tool available in the form of an application for mobile devices developed by the research team.

Detailed description: The research team will perform a randomized, controlled, concurrent, open, single-center clinical trial. The proposed intervention is the application of a protocol that uses clinical variables and the CRP value to guide the duration of antibiotic therapy in patients with suspected or confirmed bacterial infection. As for the control group, the duration of antibiotic therapy will be suggested according to the best available evidence, considering the primary site of infection and other characteristics of this process. For both groups, the study protocol will be applied through a digital application for use on smartphones or tablets, developed specifically for this project. Participants will be adults admitted to the internal medicine ward of the Hospital das Clínicas of the Federal University of Minas Gerais (HC-UFMG), for whom the assistant physician team has started antibiotic therapy in the last 72 hours. Patients will be allocated after signing a free and informed consent form. Follow-up will be carried out until hospital discharge, death or 90 days, whichever occurs first. The project was submitted for consideration to the Research Ethics Committee of the Federal University of Minas Gerais (COEP-UFMG) and approved. As primary outcome, the duration of antibiotic therapy will be evaluated for the infectious episode that motivated inclusion in the study. Duration of antibiotic therapy will be measured by antimicrobial days (defined by the aggregate of days a specific antimicrobial agent was administered to an individual patient) per 1000 present days (defined by the length of time during which a given patient is at risk for antimicrobial exposure at a given institution). As secondary outcomes, the investigators will assess total exposure to antimicrobials, antibiotic-free days, user satisfaction after using the digital tool, protocol adherence rate, length of stay, estimated cost of antimicrobial therapy, all-cause hospital mortality, therapeutic failure, reinfection rate, subsequent infections with multidrug-resistant microorganisms, Clostridioides difficile infection.

Eligibility criteria: Inclusion Criteria:

* Patients over 18 years of age,
* Clinical suspicion or microbiological confirmation of bacterial infection, with initiation of antibiotic therapy in the last 72 hours.
* Signing of the free and informed consent term by the patient or companion if the patient is unable to sign it (Annex 1).
* Patient admitted to the unit participating in the study.

Exclusion Criteria:

* HIV-infected patients with a CD4 count \< 200 cells/mm3; neutropenic with neutrophil count \< 500 cells/mm3; solid organ or bone marrow transplants; patients who received chemotherapy in the last 14 days at high risk of febrile neutropenia (\> 20%), defined by the assistant team responsible for the treatment of the neoplasm; use of immunosuppressants, such as cyclophosphamide, azathioprine, cyclosporine, rituximab, tacrolimus, sirolimus or TNF inhibitors; use of corticosteroid therapy at a dose greater than 0.5mg/Kg of prednisone (or equivalent) over the last 30 days or pulse therapy in the last 14 days with these drugs; primary immunodeficiency (eg, X-linked agammaglobulinemia, common variable immunodeficiency) or patients with another condition that determines a clear impairment of immunological defenses, whether humoral, cellular or mixed.
* Conditions that require prolonged antibiotic therapy (infective endocarditis, necrotizing pneumonia, deep abscesses, osteomyelitis, complicated soft tissue infections, S. aureus bacteremia, among others), identified before randomization (ie, up to 72 hours of antibiotic therapy) .
* Patients with the perspective of hospital discharge in less than 72 hours from inclusion.
* Patients in exclusive palliative care.
* Patients with life expectancy \< 24h.

Primary outcomes:
measure: Duration of antibiotic therapy
timeFrame: From enrollment to the end of treatment.
Secondary outcomes:
measure: Total exposure to antimicrobials
timeFrame: 90 days
measure: Antibiotic-free days
timeFrame: 90 days
measure: Length of hospital stay
timeFrame: 90 days
measure: Cost estimate of antimicrobial therapy.
timeFrame: 2 years
measure: Adherence rate to the protocol in both the intervention and control groups.
timeFrame: 90 days
measure: All-cause 90 days mortality
timeFrame: 90 days
measure: Therapeutic failure
timeFrame: 2 days
measure: Reinfection rate
timeFrame: 90 days
measure: Subsequent infections by multidrug-resistant microorganisms
timeFrame: 90 days
measure: Clostridioides difficile infection
timeFrame: 90 days
Other outcomes:
Locations:
city: Belo Horizonte
country: Brazil
facility: Hospital das Clínicas da Universidade Federal de Minas Gerais
state: Minas Gerais
Study officials:
References:
citation: Borges I, Carneiro R, Bergo R, Martins L, Colosimo E, Oliveira C, Saturnino S, Andrade MV, Ravetti C, Nobre V; NIIMI - Nucleo Interdisciplinar de Investigacao em Medicina Intensiva. Duration of antibiotic therapy in critically ill patients: a randomized controlled trial of a clinical and C-reactive protein-based protocol versus an evidence-based best practice strategy without biomarkers. Crit Care. 2020 Jun 1;24(1):281. doi: 10.1186/s13054-020-02946-y.