CAVICOR: Impact of Ceftazidime / Avibactam Treatment vs Better Available Therapy on Mortality of Patients With Infections Caused by Carbapenem-resistant Enterobacteria
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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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 Design
Arms and Interventions
| Arm | 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.
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Outcome Measures
Primary Outcome Measures
- 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.
- 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.
Secondary Outcome Measures
- 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.
- 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.
- 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
- 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.
- 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
- Recurrence [At day 30 after the start of the treatment]
Reappearance of the infection according to the same criteria and by the same microorganism
- Safety evaluation of the treatment [At day 30 after the start of the treatment]
Number of adverse reactions related to therapy
Eligibility Criteria
Criteria
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:
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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).
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Patients with infections caused by CRE without susceptibility to ceftazidime-avibactam.
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The patient is participating in a clinical trial that involves active treatment for infections.
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Patients with cardiopulmonary no resuscitation order or with a life expectancy < 30 days.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hospital Universitario de Bellvitge | Hospitalet de Llobregat | Barcelona | Spain | 08907 |
| 2 | Hospital Universitario de Gran Canaria "Dr. Negrín" | Las Palmas De Gran Canaria | Canary Islands | Spain | 35019 |
| 3 | Hospital Universitario Marqués de Valdecilla | Santander | Cantabria | Spain | 39008 |
| 4 | Complejo Hospitalario Universitario A Coruña | A Coruña | Coruña | Spain | 15006 |
| 5 | Hospital Álvaro Cunqueiro | Vigo | Pontevedra | Spain | 36211 |
| 6 | Hospital Universitario Vall d'Hebrón | Barcelona | Spain | 08035 | |
| 7 | Hospital Clínico de Barcelona | Barcelona | Spain | 08036 | |
| 8 | Hospital San Pedro de Alcántara | Cáceres | Spain | 10003 | |
| 9 | Hospital Universitario Reina Sofía | Córdoba | Spain | 14004 | |
| 10 | Hospital Universitario de La Princesa | Madrid | Spain | 28006 | |
| 11 | Hospital General Universitario Gregorio Marañón | Madrid | Spain | 28007 | |
| 12 | Hospital Universitario Ramón y Cajal | Madrid | Spain | 28034 | |
| 13 | Hospital Universitario 12 de Octubre | Madrid | Spain | 28041 | |
| 14 | Hospital Regional Universitario de Málaga | Málaga | Spain | 29010 | |
| 15 | Hospital Clínico Universitario de Valencia | Valencia | Spain | 46010 | |
| 16 | Hospital General Universitario de Valencia | Valencia | Spain | 46014 | |
| 17 | Hospital Universitario y Politécnico La Fe | Valencia | Spain | 46026 |
Sponsors and Collaborators
- Maimónides Biomedical Research Institute of Córdoba
Investigators
- Principal Investigator: Juan José Castón Osorio, MD, Hospital Universitario Reina Sofía
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- FCO-CAV-2018-01