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

Carbapenem-Resistant Enterobacteriaceae Infection Clinical Trial

— CAVICOR  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04167228
• Other study ID #: FCO-CAV-2018-01
• Status: Completed
• Start date: October 1, 2019
• Est. completion date: May 5, 2021

Study information

• Verified date: July 2021
• Source: Maimónides Biomedical Research Institute of Córdoba
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 348
• Est. completion date: May 5, 2021
• Est. primary completion date: July 15, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Ceftazidime-Avibactam
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.
• Best Available Therapy
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 the best available treatment other than ceftazidime-avibactam.

Locations

Country	Name	City	State
Spain	Complejo Hospitalario Universitario A Coruña	A Coruña	Coruña
Spain	Hospital Clínico de Barcelona	Barcelona
Spain	Hospital Universitario Vall d'Hebrón	Barcelona
Spain	Hospital San Pedro de Alcántara	Cáceres
Spain	Hospital Universitario Reina Sofía	Córdoba
Spain	Hospital Universitario de Bellvitge	Hospitalet de Llobregat	Barcelona
Spain	Hospital Universitario de Gran Canaria "Dr. Negrín"	Las Palmas De Gran Canaria	Canary Islands
Spain	Hospital General Universitario Gregorio Marañón	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario de La Princesa	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Hospital Regional Universitario de Málaga	Málaga
Spain	Hospital Universitario Marqués de Valdecilla	Santander	Cantabria
Spain	Hospital Clínico Universitario de Valencia	Valencia
Spain	Hospital General Universitario de Valencia	Valencia
Spain	Hospital Universitario y Politécnico La Fe	Valencia
Spain	Hospital Álvaro Cunqueiro	Vigo	Pontevedra

Sponsors (1)

Lead Sponsor	Collaborator
Maimónides Biomedical Research Institute of Córdoba

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	30-day mortality rate	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.	At day 30 after the start of the treatment
Primary	Clinical response on day 21	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.	At day 21 after the start of the treatment
Secondary	Microbiological response	Microbiological response in the Test-of-cure, categorized as eradication, microbiological failure or uncertain.	At day 30 after the start of the treatment
Secondary	30-day mortality rate in the group of patients with caz-avi in monotherapy and in the group with combined therapy with caz-avi	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.	At day 30 after the start of the treatment
Secondary	Risk factors associated with the development of resistance to ceftazidime-avibactam during treatmen	Describe the rates and risk factors associated with the development of resistance to ceftazidime-avibactam (MIC> 8 microg / mL) during treatment	At day 30 after the start of the treatment
Secondary	Duration of hospital stay after infection	Number of days elapsed from the end of antibiotic treatment until discharge and duration of ICU stay if appropriate.	At day 30 after the start of the treatment
Secondary	Duration of antibiotic treatment during the episode	Number of days of antibiotic treatment during the episode	At day 30 after the start of the treatment
Secondary	Recurrence	Reappearance of the infection according to the same criteria and by the same microorganism	At day 30 after the start of the treatment
Secondary	Safety evaluation of the treatment	Number of adverse reactions related to therapy	At day 30 after the start of the treatment