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

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.

Study Overview

• Status: Completed
• Conditions: Carbapenem-Resistant Enterobacteriaceae Infection
• Intervention / Treatment: Drug: Ceftazidime-Avibactam; Drug: Best Available Therapy

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 Type: Observational
• Enrollment (Actual): 348

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron
  • Barcelona, Spain, 08036
    • Hospital Clínico de Barcelona
  • Cáceres, Spain, 10003
    • Hospital San Pedro de Alcántara
  • Córdoba, Spain, 14004
    • Hospital Universitario Reina Sofia
  • Madrid, Spain, 28034
    • Hospital Universitario Ramón y Cajal
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28006
    • Hospital Universitario de La Princesa
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañón
  • Málaga, Spain, 29010
    • Hospital Regional Universitario de Malaga
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia
  • Valencia, Spain, 46026
    • Hospital Universitario y Politecnico La Fe
  • Valencia, Spain, 46014
    • Hospital General Universitario de Valencia
  • Barcelona
    • Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Hospital Universitario de Bellvitge
  • Canary Islands
    • Las Palmas De Gran Canaria, Canary Islands, Spain, 35019
      • Hospital Universitario de Gran Canaria "Dr. Negrin"
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Marqués de Valdecilla
  • Coruña
    • A Coruña, Coruña, Spain, 15006
      • Complejo Hospitalario Universitario A Coruna
  • Pontevedra
    • Vigo, Pontevedra, Spain, 36211
      • Hospital Álvaro Cunqueiro

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with infections caused by carbapenem resistant enterobacteria

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
CRE infected patients treated with ceftazidime-avibactam; Patients with infections caused by carbapenem resistant enterobacteria treated with ceftazidime-avibactam	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.
CRE infected patients treated with best available treatment; Patients with infections caused by carbapenem resistant enterobacteria treated with the best available treatment	Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
Recurrence	Reappearance of the infection according to the same criteria and by the same microorganism	At day 30 after the start of the treatment
Safety evaluation of the treatment	Number of adverse reactions related to therapy	At day 30 after the start of the treatment

Collaborators and Investigators

• Sponsor: Maimónides Biomedical Research Institute of Córdoba
• Investigators: Principal Investigator: Juan José Castón Osorio, MD, Hospital Universitario Reina Sofia

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2019
• Primary Completion (Actual): July 15, 2020
• Study Completion (Actual): May 5, 2021

Study Registration Dates

• First Submitted: November 14, 2019
• First Submitted That Met QC Criteria: November 15, 2019
• First Posted (Actual): November 18, 2019

Study Record Updates

• Last Update Posted (Actual): July 20, 2021
• Last Update Submitted That Met QC Criteria: July 19, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: ceftazidime / avibactam; carbapenem resistant enterobacteria
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Communicable Diseases; Enterobacteriaceae Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Avibactam; Ceftazidime; Avibactam, ceftazidime drug combination
• Other Study ID Numbers: FCO-CAV-2018-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: The information collected will be of public access by request.
• IPD Sharing Time Frame: After the trial results are public.
• IPD Sharing Access Criteria: By request to uicec@imibic.org
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No