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

NCT05210387 | Terminated DMC

• 1 other identifier: 47366621.1.1001.5330
• Study Type: interventional
• Target: 107
• Locations: 1 country
• Sites: 29

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

Outcome Measures

Primary Outcomes (1)

• Clinical failure

  Incidence of clinical failure. Clinical failure is a composite outcome defined by the presence of one of the following: Infection relapse (infection anywhere in the body by the same MDR-GNB) or Death

  28 days after randomization

Secondary Outcomes (9)

• Days alive and free from hospitalization

  28 days after randomization

• Days alive and free from any antibiotic therapy

  28 days after randomization

• Occurrence of infections caused by other MRD-GNB or other bacteria

  28 days after randomization

• Length of intensive care unit stay

  28 days after randomization

• Acute kidney injury

  28 days after randomization

Study Arms (2)

7-day adequate antibiotic therapy

EXPERIMENTAL

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

Other: Duration of therapy

14-day adequate antibiotic therapy

ACTIVE COMPARATOR

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

Other: Duration of therapy

Interventions

Duration of therapy 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; 7-day adequate antibiotic therapy

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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)
• Known pregnancy
• Patient in palliative care who has already decided not to restart antimicrobials, if necessary, or hemodynamic support measures.

Sponsors & Collaborators

• Hospital Moinhos de Vento: lead

Study Sites (29)

Hospital OTO clinica

Fortaleza, Ceará, Brazil

Location

Hospital Evangélico de Vila Velha

Vila Velha, Espírito Santo, 29118-060, Brazil

Location

Hospital Cleriston de Andrade

Feira de Santana, Estado de Bahia, 44089-340, Brazil

Location

Hospital Couto Maia

Salvador, Estado de Bahia, Brazil

Location

Hospital da Cidade

Salvador, Estado de Bahia, Brazil

Location

Instituto Hospital de Base do Distrito Federal

Brasília, Federal District, 70330-150, Brazil

Location

Hospital Universitário de Brasília

Brasília, Federal District, 70840-901, Brazil

Location

Hospital Presidente Vargas

São Luís, Maranhão, 65040-450, Brazil

Location

Santa Casa de Misericórdia de Belo Horizonte

Belo Horizonte, Minas Gerais, 30150-221, Brazil

Location

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

Nova Lima, Minas Gerais, 34000-000, Brazil

Location

Irmandade da Santa Casa de Misericórdia de Passos

Passos, Minas Gerais, 37904-020, Brazil

Location

Hospital Universitário da Universidade Estadual de Londrina

Londrina, Paraná, 86038-350, Brazil

Location

Hospital Municipal de Maringá

Maringá, Paraná, 87053-270, Brazil

Location

Hospital Regional Baixo Amazonas

Santarém, Pará, Brazil

Location

Hospital do Tricentenário

Olinda, Pernambuco, 53120-420, Brazil

Location

Hospital São João Batista

Volta Redonda, Rio de Janeiro, Brazil

Location

Hospital Tacchini

Bento Gonçalves, Rio Grande do Sul, 95700-068, Brazil

Location

Hospital Geral Caxias do Sul

Caxias do Sul, Rio Grande do Sul, 95070-561, Brazil

Location

Hospital de Clinicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

Location

Hospital Ernesto Dornelles

Porto Alegre, Rio Grande do Sul, 90160-092, Brazil

Location

Hospital Nossa Senhora da Conceição

Porto Alegre, Rio Grande do Sul, Brazil

Location

Hospital São Lucas da PUC

Porto Alegre, Rio Grande do Sul, Brazil

Location

Hospital Santa Cruz

Santa Cruz do Sul, Rio Grande do Sul, 96810-072, Brazil

Location

Hospital Ana Nery

Santa Cruz do Sul, Rio Grande do Sul, 96835-090, Brazil

Location

Hospital São Lucas Sergipe - Rede D´or São Luiz

Aracaju, Sergipe, Brazil

Location

Hospital Dr. Léo Orsi Bernadres - HLOB

Itapetininga, São Paulo, 18.030-070, Brazil

Location

Hospital Naval Marcílio Dias

Rio de Janeiro, Brazil

Location

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

Rio de Janeiro, Brazil

Location

Hospital A.C Camargo

São Paulo, Brazil

Location

Related Publications (2)

• 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.

  PMID: 39695798 DERIVED

• 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.

  PMID: 38102448 DERIVED

MeSH Terms

Conditions

Sepsis; Infections; Pseudomonas Infections; Acinetobacter Infections; Gram-Negative Bacterial Infections; Bacteremia

Interventions

Duration of Therapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Patient Care; Therapeutics; Health Services; Health Care Facilities Workforce and Services

Study Officials

• Alexandre Prehn Zavascki

  Hospital Moinhos de Vento

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 31, 2021
• First Posted: January 27, 2022
• Study Start: January 27, 2022
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: March 6, 2024

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

BR (29)