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

NCT05841875 | Completed

• 1 other identifier: BIO.RAP
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

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.

Conditions

Systemic Infection

Keywords

Systemic infection; Sepsis; Biomarkers; C reactive protein; Antibiotic; Antibiotic stewardship

Outcome Measures

Primary Outcomes (1)

• Duration of antibiotic therapy

  Duration of antibiotic therapy for the index infectious episode (the one that prompted inclusion in the study), measured in days.

  From enrollment to the end of treatment.

Secondary Outcomes (10)

• Total exposure to antimicrobials

  90 days

• Antibiotic-free days

  90 days

• Length of hospital stay

  90 days

• Cost estimate of antimicrobial therapy.

  2 years

• Adherence rate to the protocol in both the intervention and control groups.

  90 days

Study Arms (2)

Intervention group - C reactive protein

EXPERIMENTAL

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.

Other: C reactive protein algorithm

Control group: Best practice

NO INTERVENTION

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.

Interventions

C reactive protein algorithm 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.

Intervention group - C reactive protein

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 in exclusive palliative care.
• Patients with life expectancy \< 24h.

Sponsors & Collaborators

• Federal University of Minas Gerais: lead
• Conselho Nacional de Desenvolvimento Científico e Tecnológico: collaborator
• FAPEMIG - Fundação de Amparo a Pesquisa do Estado de Minas Gerais: collaborator

Study Sites (1)

Hospital das Clínicas da Universidade Federal de Minas Gerais

Belo Horizonte, Minas Gerais, 30130100, Brazil

Location

Related Publications (2)

• 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.

  PMID: 32487263 BACKGROUND

• 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.

  PMID: 39870501 DERIVED

MeSH Terms

Conditions

Toxemia; Sepsis

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Model Details: Parallel Assignment

Study Record Dates

• First Submitted: March 28, 2023
• First Posted: May 3, 2023
• Study Start: April 3, 2023
• Primary Completion: October 30, 2024
• Study Completion: October 30, 2024
• Last Updated: August 12, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: Initially, the database generated by this project will remain restricted to the research team. Data sharing is anticipated at the time of associated publications, following proper anonymization of patient information. Data may be shared with journal editors or reviewers as part of the manuscript evaluation process, in compliance with journal requirements.
• Access Criteria: Access to the scientific data will be limited to the research team via a permission-based system that requires login credentials. The serum samples stored in the biorepository will be similarly restricted, with access controlled in compliance with the Institutional Biorepository Regulations of the hosting institution. All data will be de-identified prior to sharing or distribution. A certificate of confidentiality will be included as part of the Informed Consent process to further safeguard participants privacy and rights.

Locations

BR (1)