Clinical trial NCT05210387: Seven Versus 14 Days of Antibiotic Therapy for Multidrug-resistant Gram-negative Bacilli Infections
Official title: Open-label, Randomized Clinical Trial to Assess the Non-inferiority of 7-day Antibiotic Therapy Compared to Conventional 14-day Treatment in Multidrug-resistant Gram-negative Bacilli Infections
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Carbapenem-Resistant Enterobacteriaceae Infection
Bloodstream Infection
Severe Infection
Pseudomonas Aeruginosa
Acinetobacter Infections
Gram-Negative Bacterial Infections
Human
Carbapenem Resistant Bacterial Infection
Bacteremia
Sepsis
Lead sponsor: Hospital Moinhos de Vento
Sponsor class: OTHER
First posted: 2022-01-27
Enrollment: 107
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Clinical failure
timeFrame: 28 days after randomization
Secondary outcomes:
measure: Days alive and free from hospitalization
timeFrame: 28 days after randomization
measure: Days alive and free from any antibiotic therapy
timeFrame: 28 days after randomization
measure: Occurrence of infections caused by other MRD-GNB or other bacteria
timeFrame: 28 days after randomization
measure: Length of intensive care unit stay
timeFrame: 28 days after randomization
measure: Acute kidney injury
timeFrame: 28 days after randomization
measure: Diarrhea for any cause
timeFrame: 28 days after randomization
measure: Confirmed infection by Clostridioides difficile
timeFrame: 28 days after randomization
measure: Hemodynamic instability lasting more than 6 hours
timeFrame: 14 days after randomization
measure: Other adverse events related to antimicrobial therapy
timeFrame: 28 days after randomization
Other outcomes:
Locations:
city: Feira De Santana
country: Brazil
facility: Hospital Cleriston de Andrade
state: Bahia
city: Salvador
country: Brazil
facility: Hospital Couto Maia
state: Bahia
city: Salvador
country: Brazil
facility: Hospital da Cidade
state: Bahia
city: Fortaleza
country: Brazil
facility: Hospital OTO clinica
state: Ceará
city: Brasília
country: Brazil
facility: Instituto Hospital de Base do Distrito Federal
state: Distrito Federal
city: Brasília
country: Brazil
facility: Hospital Universitário de Brasília
state: Distrito Federal
city: Vila Velha
country: Brazil
facility: Hospital Evangélico de Vila Velha
state: Espirito Santo
city: São Luís
country: Brazil
facility: Hospital Presidente Vargas
state: Maranhão
city: Belo Horizonte
country: Brazil
facility: Santa Casa de Misericórdia de Belo Horizonte
state: Minas Gerais
city: Nova Lima
country: Brazil
facility: Hospital Vila da Serra (Instituto Materno Infantil de Minas Gerais S/A)
state: Minas Gerais
city: Passos
country: Brazil
facility: Irmandade da Santa Casa de Misericórdia de Passos
state: Minas Gerais
city: Londrina
country: Brazil
facility: Hospital Universitário da Universidade Estadual de Londrina
state: Paraná
city: Maringá
country: Brazil
facility: Hospital Municipal de Maringá
state: Paraná
city: Santarém
country: Brazil
facility: Hospital Regional Baixo Amazonas
state: Pará
city: Olinda
country: Brazil
facility: Hospital do Tricentenário
state: Pernambuco
city: Volta Redonda
country: Brazil
facility: Hospital São João Batista
state: Rio De Janeiro
city: Bento Gonçalves
country: Brazil
facility: Hospital Tacchini
state: Rio Grande Do Sul
city: Caxias Do Sul
country: Brazil
facility: Hospital Geral Caxias do Sul
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Hospital Ernesto Dornelles
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Hospital Nossa Senhora da Conceição
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Hospital São Lucas da PUC
state: Rio Grande Do Sul
city: Santa Cruz Do Sul
country: Brazil
facility: Hospital Santa Cruz
state: Rio Grande Do Sul
city: Santa Cruz Do Sul
country: Brazil
facility: Hospital Ana Nery
state: Rio Grande Do Sul
city: Aracaju
country: Brazil
facility: Hospital São Lucas Sergipe - Rede D´or São Luiz
state: Sergipe
city: Itapetininga
country: Brazil
facility: Hospital Dr. Léo Orsi Bernadres - HLOB
state: São Paulo
city: Rio De Janeiro
country: Brazil
facility: Hospital Naval Marcílio Dias
city: Rio De Janeiro
country: Brazil
facility: Instituto Estadual do Cérebro Paulo Niemeyer (Pró Saúde- Associação Beneficente de Assistência Social e Hospitalar)
city: São Paulo
country: Brazil
facility: Hospital A.C Camargo
Study officials:
affiliation: Hospital Moinhos de Vento
name: Alexandre Prehn Zavascki
role: PRINCIPAL_INVESTIGATOR
References: