Impact of Ceftazidime / Avibactam Treatment vs Better Available Therapy on Mortality of Patients With Infections Caused by Carbapenem-resistant Enterobacteria

Completed

• Conditions: Carbapenem-Resistant Enterobacteriaceae Infection
• Interventions: Drug: Ceftazidime-Avibactam; Drug: Best Available Therapy

• Registration Number: NCT04167228
• Lead Sponsor: Maimónides Biomedical Research Institute of Córdoba

Brief Summary

Patients with infections caused by carbapenem-resistant enterobacteria treated with CAZ-AVI versus patients treated with BAT are compared. The BAT group includes fosfomycin, tigecycline, gentamicin, meropenem and colistin.

Detailed Description

Carbapenem-resistant enterobacteria (CRE) are a public health problem. The morbidity and mortality of patients with invasive infections due to CRE are high. The best treatment is unknown, however, combination therapy with at least 2 active drugs is often recommended for high-risk patients, and monotherapy is probably not inferior to this in low-risk patients.

Ceftazidime-avibactam is active against many CRE, and in some countries it has been prescribed under compassionate use programs for these infections; It has recently been approved by the FDA and the EMA for specific indications. Recent data suggest that ceftazidime-avibactam may be superior for the treatment of infections caused by sensitive CRE, rather than traditional regimens that often include colistin, usually combined with other drugs. However, these studies include a low number of patients and are subject to important biases.

Additionally, the development of resistance to this drug during / after treatment has been described and is worrying.

Study Timeline

• Study Start: 2019-10-01
• Study First Submitted: 2019-11-14
• Study First Submitted QC: 2019-11-15
• Study First Posted: 2019-11-18
• Primary Completion: 2020-07-15
• Study Completion: 2021-05-05
• Status Verified: 2021-07
• Last Update Submitted: 2021-07-19
• Last Update Posted: 2021-07-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 348

Inclusion Criteria

• Patients with complicated urinary tract infections, nosocomial pneumonia (including pneumonia associated with ventilation), complicated intra-abdominal infections or bacteremia (if the focus of infection is any of the above, the patient should be included in both groups) due to CRE, treated > 2 days with ceftazidime-avibactam. Patients with bacteremia can be included in one of the other cohorts if the focus of the infection is the urinary tract, respiratory tract or an intra-abdominal infection and they meet the appropriate criteria (see below). The retrospective design of this study has been carried out to avoid the induction of the prescription of ceftazidime-avibactam in each center. For this, patients will be included at the end of the period of evaluation of the primary objective (crude mortality at day 30). If more than one patient can be used as a control, the one with the closest admission date will be chosen.

Control: local historical cohort - Patients treated with ceftazidime-avibactam will be compared with patients treated with BAT. Because after approval of the use of ceftazidime-avibactam, BAT could be used less frequently to treat this type of infection, patients treated with BAT from January 1, 2014 will be included. These patients will be matched by hospital, type of hospital. infection (urinary tract vs others) and INCREMENT score.

Exclusion Criteria

• The infection is considered polymicrobial according to the standard microbiological interpretation of the crop results (except for complicated intra-abdominal infections, in which case, polymicrobial infections are allowed).
• Patients with infections caused by CRE without susceptibility to ceftazidime-avibactam.
• The patient is participating in a clinical trial that involves active treatment for infections.
• Patients with cardiopulmonary no resuscitation order or with a life expectancy < 30 days.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
CRE infected patients treated with ceftazidime-avibactam	Ceftazidime-Avibactam	Patients with infections caused by carbapenem resistant enterobacteria treated with ceftazidime-avibactam
CRE infected patients treated with best available treatment	Best Available Therapy	Patients with infections caused by carbapenem resistant enterobacteria treated with the best available treatment

Primary Outcome Measures

Name	Time	Method
Clinical response on day 21	At day 21 after the start of the treatment	To describe the clinical response on day 21 of the caz-avi group and in the group with the best available therapy of patients with infections caused by carbapenem-resistant enterobacteria.
30-day mortality rate	At day 30 after the start of the treatment	To describe the 30-day mortality rate in the caz-avi group and in the group with the best available therapy of patients with infections caused by carbapenem-resistant enterobacteria.

Secondary Outcome Measures

Name	Time	Method
Duration of antibiotic treatment during the episode	At day 30 after the start of the treatment	Number of days of antibiotic treatment during the episode
30-day mortality rate in the group of patients with caz-avi in monotherapy and in the group with combined therapy with caz-avi	At day 30 after the start of the treatment	Describe the 30-day mortality rate in the group of patients with caz-avi in monotherapy and in the group with combined therapy with caz-avi, who present with infections caused by carbapenem-resistant enterobacteria.
Duration of hospital stay after infection	At day 30 after the start of the treatment	Number of days elapsed from the end of antibiotic treatment until discharge and duration of ICU stay if appropriate.
Microbiological response	At day 30 after the start of the treatment	Microbiological response in the Test-of-cure, categorized as eradication, microbiological failure or uncertain.
Risk factors associated with the development of resistance to ceftazidime-avibactam during treatmen	At day 30 after the start of the treatment	Describe the rates and risk factors associated with the development of resistance to ceftazidime-avibactam (MIC\> 8 microg / mL) during treatment
Safety evaluation of the treatment	At day 30 after the start of the treatment	Number of adverse reactions related to therapy
Recurrence	At day 30 after the start of the treatment	Reappearance of the infection according to the same criteria and by the same microorganism

Trial Locations

Locations (17)

Hospital Universitario Vall d'Hebrón; 🇪🇸 Barcelona, Spain

Hospital Universitario de Gran Canaria "Dr. Negrín"; 🇪🇸 Las Palmas De Gran Canaria, Canary Islands, Spain

Hospital Universitario Ramón y Cajal; 🇪🇸 Madrid, Spain

Hospital Universitario de Bellvitge; 🇪🇸 Hospitalet de Llobregat, Barcelona, Spain

Complejo Hospitalario Universitario A Coruña; 🇪🇸 A Coruña, Coruña, Spain

Hospital General Universitario Gregorio Marañón; 🇪🇸 Madrid, Spain

Hospital Clínico de Barcelona; 🇪🇸 Barcelona, Spain

Hospital Universitario Reina Sofía; 🇪🇸 Córdoba, Spain

Hospital San Pedro de Alcántara; 🇪🇸 Cáceres, Spain

Hospital Universitario Marqués de Valdecilla; 🇪🇸 Santander, Cantabria, Spain

Hospital Universitario de La Princesa; 🇪🇸 Madrid, Spain

Hospital Clínico Universitario de Valencia; 🇪🇸 Valencia, Spain

Hospital Universitario y Politécnico La Fe; 🇪🇸 Valencia, Spain

Hospital Regional Universitario de Málaga; 🇪🇸 Málaga, Spain

Hospital Universitario 12 de Octubre; 🇪🇸 Madrid, Spain

Hospital General Universitario de Valencia; 🇪🇸 Valencia, Spain

Hospital Álvaro Cunqueiro; 🇪🇸 Vigo, Pontevedra, Spain