Efficacy and Safety of a Protocol Using C-reactive Protein to Guide Antibiotic Therapy

NCT ID: NCT05841875

Last Updated: 2025-08-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 110 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-04-03
• Study Completion Date: 2024-10-30

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.

Conditions

Systemic Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intervention group - C reactive protein

For patients in the intervention group, attending physicians will be encouraged to follow an algorithm that uses clinical variables and serum CRP levels to guide the duration of antibiotic therapy. The peak CRP is defined as the highest value recorded within the first 72 hours of treatment.

Antibiotic therapy discontinuation will be encouraged under the following conditions:

If the peak CRP is below 100 mg/L: Consider stopping antibiotics when CRP falls below 35 mg/L, with a minimum treatment duration of 3 days.

If the peak CRP is above 100 mg/L or the patient meets criteria for sepsis or septic shock: Consider stopping antibiotics when CRP has decreased by 50%, after a minimum of 5 days.

If the patient does not meet the CRP criteria: Antibiotic discontinuation will be recommended after 5-7 days, provided there is clinical improvement.

Group Type: EXPERIMENTAL

C reactive protein algorithm

Intervention Type: OTHER

Antibiotic therapy discontinuation will be encouraged under the following conditions:

If the peak CRP is below 100 mg/L: Consider stopping antibiotics when CRP falls below 35 mg/L, with a minimum treatment duration of 3 days.

If the peak CRP is above 100 mg/L or the patient meets criteria for sepsis or septic shock: Consider stopping antibiotics when CRP has decreased by 50%, after a minimum of 5 days.

If the patient does not meet the CRP criteria: Antibiotic discontinuation will be recommended after 5-7 days, provided there is clinical improvement.

Before discontinuing antibiotic therapy, physicians should confirm that the patient is clinically improving, with no signs of a persistent infectious focus. Additionally, they will be encouraged to verify that the Sequential Organ Failure Assessment (SOFA) score is stable or decreasing. These factors will assist in determining the appropriateness of stopping antibiotics.

Control group: Best practice

For patients in the control group, the attending physician will be encouraged to determine the duration of antimicrobial therapy based on the best available evidence, taking into account the most likely infectious focus and the patient's clinical response. These recommendations will be guided by international society guidelines and established best practices for antibiotic therapy.

Additionally, it is recommended that CRP monitoring in the control group be discontinued after 72 hours of antibiotic therapy, as this period is considered sufficient for using CRP as a biomarker to assist in diagnosing the infectious condition.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

C reactive protein algorithm

Antibiotic therapy discontinuation will be encouraged under the following conditions:

If the peak CRP is below 100 mg/L: Consider stopping antibiotics when CRP falls below 35 mg/L, with a minimum treatment duration of 3 days.

If the peak CRP is above 100 mg/L or the patient meets criteria for sepsis or septic shock: Consider stopping antibiotics when CRP has decreased by 50%, after a minimum of 5 days.

If the patient does not meet the CRP criteria: Antibiotic discontinuation will be recommended after 5-7 days, provided there is clinical improvement.

Before discontinuing antibiotic therapy, physicians should confirm that the patient is clinically improving, with no signs of a persistent infectious focus. Additionally, they will be encouraged to verify that the Sequential Organ Failure Assessment (SOFA) score is stable or decreasing. These factors will assist in determining the appropriateness of stopping antibiotics.

Intervention Type: OTHER

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Conselho Nacional de Desenvolvimento Científico e Tecnológico

OTHER_GOV

Sponsor Role: collaborator

FAPEMIG - Fundação de Amparo a Pesquisa do Estado de Minas Gerais

UNKNOWN

Sponsor Role: collaborator

Federal University of Minas Gerais

OTHER

Sponsor Role: lead

Responsible Party

Vandack Alencar Nobre

Clinical Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Hospital das Clínicas da Universidade Federal de Minas Gerais

Belo Horizonte, Minas Gerais, Brazil

Countries

Brazil

References

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.

Reference Type: BACKGROUND

PMID: 32487263 (View on PubMed)

Rezende VMLR, Borges IN, Ravetti CG, De Souza RP, Vassalo PF, Caldas ACP, Gatto FR, Okamura GH, Lacerda RLB, Povoa PR, Nobre V. Efficacy and safety of an algorithm using C-reactive protein to guide antibiotic therapy applied through a digital clinical decision support system: a study protocol for a randomised controlled clinical trial. BMJ Open. 2025 Jan 27;15(1):e084981. doi: 10.1136/bmjopen-2024-084981.

Reference Type: DERIVED

PMID: 39870501 (View on PubMed)

Other Identifiers

BIO.RAP

Identifier Type: -

Identifier Source: org_study_id