Seven Versus 14 Days of Antibiotic Therapy for Multidrug-resistant Gram-negative Bacilli Infections

NCT ID: NCT05210387

Last Updated: 2024-03-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 107 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-27
• Study Completion Date: 2023-12-31

Brief Summary

Antimicrobial resistance is a major global problem, particularly in hospital-acquired infections (HAIs). Gram-negative bacilli (GNB), including Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii, are among the most common pathogens associated with multidrug resistance and HAIs. These bacteria are of special concern because few therapeutic options are available.

Traditionally, the duration of treatment for severe multidrug-resistant (MDR)-GNB infections is 14 days. Studies of severe infections by GNB, regardless of susceptibility profile, have shown that shorter antimicrobial treatments are not inferior to traditional durations of therapy and are associated with a lower incidence of adverse effects. However, there are currently no studies assessing whether shorter duration of antimicrobial treatment is effective for MDR-GNB.

This open-label, randomized clinical trial aims to assess the non-inferiority of 7-day antibiotic therapy compared to conventional 14-day treatment in severe infections by MDR-GNB.

Conditions

Carbapenem-Resistant Enterobacteriaceae Infection; Bloodstream Infection; Severe Infection; Pseudomonas Aeruginosa; Acinetobacter Infections; Gram-Negative Bacterial Infections; Human; Carbapenem Resistant Bacterial Infection; Bacteremia; Sepsis

Study Design

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

Study Groups

7-day adequate antibiotic therapy

Adequate antibiotic therapy is defined as antimicrobial treatment with at least one agent with in vitro susceptibility.

Group Type: EXPERIMENTAL

Duration of therapy

Intervention Type: OTHER

In experimental group patients with severe infection caused by MDR-GNB and who present a clinical response on day 7 (±1) of adequate antimicrobial therapy, the therapy will be suspended.

The active control group will continue therapy until day 14 (±1).

14-day adequate antibiotic therapy

Adequate antibiotic therapy is defined as antimicrobial treatment with at least one agent with in vitro susceptibility.

Group Type: ACTIVE_COMPARATOR

Duration of therapy

Intervention Type: OTHER

In experimental group patients with severe infection caused by MDR-GNB and who present a clinical response on day 7 (±1) of adequate antimicrobial therapy, the therapy will be suspended.

The active control group will continue therapy until day 14 (±1).

Interventions

Duration of therapy

In experimental group patients with severe infection caused by MDR-GNB and who present a clinical response on day 7 (±1) of adequate antimicrobial therapy, the therapy will be suspended.

The active control group will continue therapy until day 14 (±1).

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Infection's diagnosis while in the ICU
• Severe infection in any site (defined as the presence of sepsis/septic shock or bloodstream infection or pneumonia) associated with a positive culture by MRD-GNB (Acinetobacter baumannii complex, Pseudomonas aeruginosa, and Enterobacterales bacteria, only susceptible to carbapenems and/or polymyxins)
• Hemodynamically stable and afebrile (axillary temperature less than 37.8ºC) for at least 48 hours on day 7 of adequate antibiotic therapy
• Consent of the team providing care to the patient regarding their inclusion in the research

Exclusion Criteria

• Inclusion in other experimental studies involving antimicrobial therapy
• Infections that have as the primary site: endocarditis/endovascular infection, necrotizing fasciitis, osteomyelitis, abdominal abscess or other abdominal infections requiring surgical intervention (except infections that have been treated surgically, with curative character within the first 3 days of appropriate antimicrobial therapy), central nervous system Infections, empyema, prosthetic infection;
• Immunosuppression defined as: neutrophil cells <1000/mm³ in the current hospitalization, HIV/AIDS diagnosis with last CD4 count <200/mm³, solid organ transplantation in the last year and/or need for increased immunosuppression due to acute rejection in the last year, hematopoietic stem cell transplantation in the last year, and/or current therapy for chronic graft-versus-host disease
• Positive blood cultures for the same pathogen within 48 hours prior to randomization, when collected
• Uncontrolled concomitant infection with another GNB (regardless of susceptibility profile)
• Previous inclusion in this study
• Known pregnancy
• Patient in palliative care who has already decided not to restart antimicrobials, if necessary, or hemodynamic support measures.

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

Sponsors

Hospital Moinhos de Vento

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alexandre Prehn Zavascki

Role: PRINCIPAL_INVESTIGATOR

Hospital Moinhos de Vento

Locations

Hospital OTO clinica

Fortaleza, Ceará, Brazil

Hospital Evangélico de Vila Velha

Vila Velha, Espírito Santo, Brazil

Hospital Cleriston de Andrade

Feira de Santana, Estado de Bahia, Brazil

Hospital Couto Maia

Salvador, Estado de Bahia, Brazil

Hospital da Cidade

Salvador, Estado de Bahia, Brazil

Instituto Hospital de Base do Distrito Federal

Brasília, Federal District, Brazil

Hospital Universitário de Brasília

Brasília, Federal District, Brazil

Hospital Presidente Vargas

São Luís, Maranhão, Brazil

Santa Casa de Misericórdia de Belo Horizonte

Belo Horizonte, Minas Gerais, Brazil

Hospital Vila da Serra (Instituto Materno Infantil de Minas Gerais S/A)

Nova Lima, Minas Gerais, Brazil

Irmandade da Santa Casa de Misericórdia de Passos

Passos, Minas Gerais, Brazil

Hospital Universitário da Universidade Estadual de Londrina

Londrina, Paraná, Brazil

Hospital Municipal de Maringá

Maringá, Paraná, Brazil

Hospital Regional Baixo Amazonas

Santarém, Pará, Brazil

Hospital do Tricentenário

Olinda, Pernambuco, Brazil

Hospital São João Batista

Volta Redonda, Rio de Janeiro, Brazil

Hospital Tacchini

Bento Gonçalves, Rio Grande do Sul, Brazil

Hospital Geral Caxias do Sul

Caxias do Sul, Rio Grande do Sul, Brazil

Hospital de Clinicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Hospital Ernesto Dornelles

Porto Alegre, Rio Grande do Sul, Brazil

Hospital Nossa Senhora da Conceição

Porto Alegre, Rio Grande do Sul, Brazil

Hospital São Lucas da PUC

Porto Alegre, Rio Grande do Sul, Brazil

Hospital Santa Cruz

Santa Cruz do Sul, Rio Grande do Sul, Brazil

Hospital Ana Nery

Santa Cruz do Sul, Rio Grande do Sul, Brazil

Hospital São Lucas Sergipe - Rede D´or São Luiz

Aracaju, Sergipe, Brazil

Hospital Dr. Léo Orsi Bernadres - HLOB

Itapetininga, São Paulo, Brazil

Hospital Naval Marcílio Dias

Rio de Janeiro, , Brazil

Instituto Estadual do Cérebro Paulo Niemeyer (Pró Saúde- Associação Beneficente de Assistência Social e Hospitalar)

Rio de Janeiro, , Brazil

Hospital A.C Camargo

São Paulo, , Brazil

Countries

Brazil

References

Arns B, Kalil AC, Sorio GGL, Boschi E, Antonio ACP, Antonio JP, Birriel DC, Lanziotti DH, da Cunha Abbott F, Rocha GC, de Fatima Fernandes V, de Souza Dantas VC, da Silva Medeiros GF, de Franca Diniz Rocha V, Pereira FC, Gobatto ALN, Lima VP, Lacerda FH, de Maio Carrilho CMD, de Oliveira Cardozo KDN, Irineu VM, Kurtz P, Horvath JDC, Sesin GP, Agani CAJO, Dos Santos TM, Brochier LSB, da Rosa BS, Tomazini BM, Besen BAMP, Pereira AJ, Veiga VC, Nascimento GM, Zavascki AP; OPTIMISE Study Group. Seven versus 14 days of antimicrobial therapy for severe multidrug-resistant Gram-negative bacterial infections in intensive care unit patients (OPTIMISE): a randomised, open-label, non-inferiority clinical trial. Crit Care. 2024 Dec 18;28(1):412. doi: 10.1186/s13054-024-05178-6.

Reference Type: DERIVED

PMID: 39695798 (View on PubMed)

Arns B, Horvath JDC, Rech GS, Sesin GP, Agani CAJO, da Rosa BS, Dos Santos TM, Brochier LSB, Cavalcanti AB, Tomazini BM, Pereira AJ, Veiga VC, Nascimento GM, Kalil AC, Zavascki AP. A Randomized, Open-Label, Non-inferiority Clinical Trial Assessing 7 Versus 14 Days of Antimicrobial Therapy for Severe Multidrug-Resistant Gram-Negative Bacterial Infections: The OPTIMISE Trial Protocol. Infect Dis Ther. 2024 Jan;13(1):237-250. doi: 10.1007/s40121-023-00897-9. Epub 2023 Dec 16.

Reference Type: DERIVED

PMID: 38102448 (View on PubMed)

Other Identifiers

47366621.1.1001.5330

Identifier Type: -

Identifier Source: org_study_id