Best Available Therapy With or Without Meropenem for Bloodstream Infections by Enterobacterales With High Level of Resistance to Carbapenems

Bloodstream Infection Clinical Trial

— ABOVE  

Official title:

Open-label Randomized Clinical Trial Comparing Best Available Therapy With or Without Meropenem for Bloodstream Infections by Enterobacterales With Minimal Inhibitory Concentrations for Meropenem Above 32mg/L

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04876430
• Other study ID #: 2019-0401
• Status: Terminated
• Phase: Phase 2/Phase 3
• Start date: May 4, 2021
• Est. completion date: March 7, 2022

Study information

• Verified date: August 2022
• Source: Hospital de Clinicas de Porto Alegre
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Enterobacterales resistant to carbapenem are cause of severe concern in hospital-acquired infections since therapeutic options are limited. Recently approved drugs, such as bela-lactam/beta-lactamase inhibitor, have been the drug of choice. However, its use is limited in low- and middle-income countries. Thus, therapy of these infections mostly relies on polymyxins and other old drugs.

The role of adjuvant carbapenem therapy in combination with polymyxins, aminoglycosides and other drugs is under investigation. From a pharmacokinetic/pharmacodynamic (PK/PD), there is an elevated probability that high-dose, extended infusion administered meropenem reach the PK/PD target of 40% above the minimal inhibitory concentration (MIC) of the pathogen when the MIC is 32mg/L or lower (non-susceptible isolates have MICs of 4mg/L or higher). However, the MIC is not routinely determined in clinical laboratories. In addition, high-level (above 32mg/L) resistance to carbapenems have been reported in many studies.

This open-label, randomized clinical trial aim to assess if the addition of meropenem to the best available therapy can increase the number of days alive and free of hospitalization in patients with bloodstream infections by Enterobacterales with MIC of meropenem above 32mg/L.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 13
• Est. completion date: March 7, 2022
• Est. primary completion date: March 7, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Primary or secondary bloodstream infections by any specie of the Enterobacterales family with minimum inhibitory concentration (MIC) for meropenem >32mg/L;

• Agreement of the assistant team with the inclusion of the patient in the study;

• Agreement by the patient or legal guardian to sign the informed consent form.

Exclusion Criteria:

• Known pregnancy;

• Patients belonging to the population deprived of their liberty;

• Known allergy to meropenem;

• Use of ceftazidime-avibactam (or any other new antimicrobial agent that become available in Brazil during the study period) for the treatment of the current infection;

• Infection by an Enterobacterales isolates without in vitro susceptibility to at least one antimicrobial drug;

• Bloodstream co-infection by another gram negative bacilli;

• Concomitant infection at any site by a pathogen which meropenem is indicated;

• Neutropenia (<1000 neutrophils cells/mm3)

• Death expected within 48 hours of eligibility assessment.

Related Conditions & MeSH terms

• Bloodstream Infection
• Carbapenem-Resistant Enterobacteriaceae Infection
• Communicable Diseases
• Enterobacteriaceae Infections
• Infections
• Sepsis

Intervention

Drug:
• Meropenem
Meropenem 2g every 8h for patients with glomerular filtration rate (GFR) equal or higher that 50 mL/min. Dose adjustment is recommended for patients with GFR < 50mL/min.

Locations

Country	Name	City	State
Brazil	Hospital de Clínicas de Porto Alegre	Porto Alegre	RS
Brazil	Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul	Porto Alegre	RS

Sponsors (2)

Lead Sponsor	Collaborator
Hospital de Clinicas de Porto Alegre	Conselho Nacional de Desenvolvimento Científico e Tecnológico

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Days alive and free of hospitalization	Number of days in which patients are alive and out of the hospital	60 days
Secondary	Overall mortality	Death for any cause	14, 28 and 60 days after randomization
Secondary	Antimicrobial-free days	Number of days in which patients are alive and without use of antimicrobial drugs	60 days after randomization
Secondary	Relapse of infection	Presence of infection with isolation of the same bacteria between 14 and 60 days after randomization.	60 days after randomization
Secondary	Clostridioides difficile infection	Incidence of Clostridioides difficile infection	60 days after randomization
Secondary	Acute Kidney Injury	Incidence of Acute Kidney Injury, according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria	14 days after randomization
Secondary	Meropenem-related adverse effects	Incidence of adverse effects related to meropenem, such as neurological toxicity and hypersensitivity reactions	14 days after randomization