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

Sponsor

Hospital Moinhos de Vento (Other)

Overall Status

Recruiting

CT.gov ID

NCT05210387

Collaborator

(none)

520

Enrollment

Locations

Arms

23.1

Anticipated Duration (Months)

27.4

Patients Per Site

1.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Carbapenem-Resistant Enterobacteriaceae Infection Bloodstream Infection Severe Infection Pseudomonas Aeruginosa Acinetobacter Infections Gram-Negative Bacterial Infections Human Carbapenem Resistant Bacterial Infection Bacteremia Sepsis	Other: Duration of therapy	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

520 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jan 27, 2022

Anticipated Primary Completion Date :

Dec 31, 2023

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 7-day adequate antibiotic therapy Adequate antibiotic therapy is defined as antimicrobial treatment with at least one agent with in vitro susceptibility.	Other: 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).
Active Comparator: 14-day adequate antibiotic therapy Adequate antibiotic therapy is defined as antimicrobial treatment with at least one agent with in vitro susceptibility.	Other: 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).

Arm

Intervention/Treatment

Experimental: 7-day adequate antibiotic therapy

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

Other: 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).

Active Comparator: 14-day adequate antibiotic therapy

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

Other: Duration of therapy

Outcome Measures

Primary Outcome Measures

Clinical failure [28 days after randomization]
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

Secondary Outcome Measures

Days alive and free from hospitalization [28 days after randomization]
Number of days in which patients are alive and out of the hospital
Days alive and free from any antibiotic therapy [28 days after randomization]
Number of days in which patients are alive and free from any antibiotic therapy
Occurrence of infections caused by other MRD-GNB or other bacteria [28 days after randomization]
Incidence of infections caused by other MRD-GNB or other bacteria
Length of intensive care unit stay [28 days after randomization]
Number of days in which patients stayed at intensive care unit
Acute kidney injury [28 days after randomization]
Incidence of acute kidney injury, according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria
Diarrhea for any cause [28 days after randomization]
Incidence of any diarrhea. Diarrhea is defined as 3 or more episodes per day.
Confirmed infection by Clostridioides difficile [28 days after randomization]
Incidence of Clostridioides difficile infection
Hemodynamic instability lasting more than 6 hours [14 days after randomization]
Incidence of hemodynamic instability lasting more than 6 hours. Hemodynamic instability is defined as hypotension that requires the use of doses of dopamine above 15 mcg/kg/min, epinephrine above 0.1 mcg/kg/min, or norepinephrine above 0.1 mcg/kg/min
Other adverse events related to antimicrobial therapy [28 days after randomization]
Incidence of any other adverse event related to antimicrobial therapy

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria

Patient admitted to the intensive care unit
Severe infection in any site (defined as the presence of sepsis/septic shock or bloodstream infection) 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

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, 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
Concomitant infection with another GNB (regardless of susceptibility profile)
Previous inclusion in this study
Known pregnancy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Cleriston de Andrade	Feira De Santana	Bahia	Brazil	44089-340
2	Instituto Hospital de Base do Distrito Federal	Brasília	Distrito Federal	Brazil	70330-150
3	Hospital Universitário de Brasília	Brasília	Distrito Federal	Brazil	70840-901
4	Hospital Evangélico de Vila Velha	Vila Velha	Espirito Santo	Brazil	29118-060
5	Santa Casa de Misericórdia de Belo Horizonte	Belo Horizonte	Minas Gerais	Brazil	30150-221
6	Hospital Vila da Serra (Instituto Materno Infantil de Minas Gerais S/A)	Nova Lima	Minas Gerais	Brazil	34000-000
7	Irmandade da Santa Casa de Misericórdia de Passos	Passos	Minas Gerais	Brazil	37904-020
8	Hospital Universitário da Universidade Estadual de Londrina	Londrina	Paraná	Brazil	86038-350
9	Hospital Municipal de Maringá	Maringá	Paraná	Brazil	87053-270
10	Hospital Regional Baixo Amazonas	Santarém	Pará	Brazil
11	Hospital do Tricentenário	Olinda	Pernambuco	Brazil	53120-420
12	Hospital Tacchini	Bento Gonçalves	Rio Grande Do Sul	Brazil	95700-068
13	Hospital Geral Caxias do Sul	Caxias Do Sul	Rio Grande Do Sul	Brazil	95070-561
14	Hospital de Clinicas de Porto Alegre	Porto Alegre	Rio Grande Do Sul	Brazil	90035-903
15	Hospital Ernesto Dornelles	Porto Alegre	Rio Grande Do Sul	Brazil	90160-092
16	Hospital Santa Cruz	Santa Cruz Do Sul	Rio Grande Do Sul	Brazil	96810-072
17	Hospital Ana Nery	Santa Cruz Do Sul	Rio Grande Do Sul	Brazil	96835-090
18	Instituto Estadual do Cérebro Paulo Niemeyer (Pró Saúde- Associação Beneficente de Assistência Social e Hospitalar)	Rio De Janeiro		Brazil
19	Hospital A.C Camargo	São Paulo		Brazil