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

Sepsis Clinical Trial

— OPTIMISE  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05210387
• Other study ID #: 47366621.1.1001.5330
• Status: Terminated
• Phase: N/A
• Start date: January 27, 2022
• Est. completion date: December 31, 2023

Study information

• Verified date: September 2023
• Source: Hospital Moinhos de Vento
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 107
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

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).

Locations

Country	Name	City	State
Brazil	Hospital São Lucas Sergipe - Rede D´or São Luiz	Aracaju	Sergipe
Brazil	Santa Casa de Misericórdia de Belo Horizonte	Belo Horizonte	Minas Gerais
Brazil	Hospital Tacchini	Bento Gonçalves	Rio Grande Do Sul
Brazil	Hospital Universitário de Brasília	Brasília	Distrito Federal
Brazil	Instituto Hospital de Base do Distrito Federal	Brasília	Distrito Federal
Brazil	Hospital Geral Caxias do Sul	Caxias Do Sul	Rio Grande Do Sul
Brazil	Hospital Cleriston de Andrade	Feira De Santana	Bahia
Brazil	Hospital OTO clinica	Fortaleza	Ceará
Brazil	Hospital Dr. Léo Orsi Bernadres - HLOB	Itapetininga	São Paulo
Brazil	Hospital Universitário da Universidade Estadual de Londrina	Londrina	Paraná
Brazil	Hospital Municipal de Maringá	Maringá	Paraná
Brazil	Hospital Vila da Serra (Instituto Materno Infantil de Minas Gerais S/A)	Nova Lima	Minas Gerais
Brazil	Hospital do Tricentenário	Olinda	Pernambuco
Brazil	Irmandade da Santa Casa de Misericórdia de Passos	Passos	Minas Gerais
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 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 Couto Maia	Salvador	Bahia
Brazil	Hospital da Cidade	Salvador	Bahia
Brazil	Hospital Ana Nery	Santa Cruz Do Sul	Rio Grande Do Sul
Brazil	Hospital Santa Cruz	Santa Cruz Do Sul	Rio Grande Do Sul
Brazil	Hospital Regional Baixo Amazonas	Santarém	Pará
Brazil	Hospital Presidente Vargas	São Luís	Maranhão
Brazil	Hospital A.C Camargo	São Paulo
Brazil	Hospital Evangélico de Vila Velha	Vila Velha	Espirito Santo
Brazil	Hospital São João Batista	Volta Redonda	Rio De Janeiro

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Moinhos de Vento

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Days alive and free from hospitalization	Number of days in which patients are alive and out of the hospital	28 days after randomization
Secondary	Days alive and free from any antibiotic therapy	Number of days in which patients are alive and free from any antibiotic therapy	28 days after randomization
Secondary	Occurrence of infections caused by other MRD-GNB or other bacteria	Incidence of infections caused by other MRD-GNB or other bacteria	28 days after randomization
Secondary	Length of intensive care unit stay	Number of days in which patients stayed at intensive care unit	28 days after randomization
Secondary	Acute kidney injury	Incidence of acute kidney injury, according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria	28 days after randomization
Secondary	Diarrhea for any cause	Incidence of any diarrhea. Diarrhea is defined as 3 or more episodes per day.	28 days after randomization
Secondary	Confirmed infection by Clostridioides difficile	Incidence of Clostridioides difficile infection	28 days after randomization
Secondary	Hemodynamic instability lasting more than 6 hours	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	14 days after randomization
Secondary	Other adverse events related to antimicrobial therapy	Incidence of any other adverse event related to antimicrobial therapy	28 days after randomization