Carbapenem-Resistant Enterobacteriaceae InfectionCAVICORNCT04167228
Impact of Ceftazidime / Avibactam Treatment vs Better Available Therapy on Mortality of Patients With Infections Caused by Carbapenem-resistant Enterobacteria
An observational study of Carbapenem-Resistant Enterobacteriaceae Infection, run by Maimónides Biomedical Research Institute of Córdoba at 17 sites in Spain.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carbapenem-Resistant Enterobacteriaceae Infection
- What is being tested?
- Ceftazidime-Avibactam and Best Available Therapy
- How many people
- 348 participants
- Where
- 17 sitesSpain
- Study dates
- 1 Oct 2019to 5 May 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with infections caused by carbapenem resistant enterobacteria
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
17 sites in 1 country.
17 sites in 1 country
Spain17 sites
Complejo Hospitalario Universitario A Coruña
A Coruña, Coruña, 15006
Hospital Universitario Vall d'Hebrón
Barcelona, 08035
Hospital Clínico de Barcelona
Barcelona, 08036
Hospital San Pedro de Alcántara
Cáceres, 10003
Hospital Universitario Reina Sofía
Córdoba, 14004
Hospital Universitario de Bellvitge
L'Hospitalet de Llobregat, Barcelona, 08907
Hospital Universitario de Gran Canaria "Dr. Negrín"
Las Palmas de Gran Canaria, Canary Islands, 35019
Hospital Universitario de La Princesa
Madrid, 28006
Hospital General Universitario Gregorio Marañón
Madrid, 28007
Hospital Universitario Ramón y Cajal
Madrid, 28034
Hospital Universitario 12 de Octubre
Madrid, 28041
Hospital Regional Universitario de Málaga
Málaga, 29010
Hospital Universitario Marqués de Valdecilla
Santander, Cantabria, 39008
Hospital Clínico Universitario de Valencia
Valencia, 46010
Hospital General Universitario de Valencia
Valencia, 46014
Hospital Universitario y Politécnico La Fe
Valencia, 46026
Hospital Álvaro Cunqueiro
Vigo, Pontevedra, 36211
About this study
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.
Read the 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.
- Being tested
- Ceftazidime-Avibactam, Best Available Therapy
- Keywords
- ceftazidime / avibactam, carbapenem resistant enterobacteria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ceftazidime-AvibactamDrug
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 TherapyDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| CRE infected patients treated with ceftazidime-avibactam | Patients with infections caused by carbapenem resistant enterobacteria treated with ceftazidime-avibactam Receives: Drug: Ceftazidime-Avibactam | |
| CRE infected patients treated with best available treatment | Patients with infections caused by carbapenem resistant enterobacteria treated with the best available treatment Receives: Drug: Best Available Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: At day 21 after the start of the treatment
Secondary outcomes (7)
Microbiological response
Microbiological response in the Test-of-cure, categorized as eradication, microbiological failure or uncertain.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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
Measured: At day 30 after the start of the treatment
Recurrence
Reappearance of the infection according to the same criteria and by the same microorganism
Measured: At day 30 after the start of the treatment
Safety evaluation of the treatment
Number of adverse reactions related to therapy
Measured: At day 30 after the start of the treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2019
- Study start1 Oct 2019
- Primary completion15 Jul 2020
- Study completion5 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carbapenem-Resistant Enterobacteriaceae InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 348 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maimónides Biomedical Research Institute of Córdoba
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Juan José Castón Osorio, MD, Principal investigator, Hospital General Universitario Reina Sofía de Murcia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04167228
- Sponsor's protocol ID
- FCO-CAV-2018-01
- Acronym
- CAVICOR
- Status last verified
- Jul 2021
- First submitted
- 14 Nov 2019
- Last updated
- 20 Jul 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The information collected will be of public access by request.
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Ceftazidime / Avibactam Treatment vs Better Available Therapy on Mortality of Patients With Infections Caused by Carbapenem-resistant Enterobacteria
- ClinicalTrials.gov ID
- NCT04167228
- Acronym / sponsor ID
- CAVICOR / FCO-CAV-2018-01
- Keywords
- ceftazidime / avibactam, carbapenem resistant enterobacteria
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 348 participants (actual)
- Lead sponsor
- Maimónides Biomedical Research Institute of CórdobaUniversity, hospital or other
- Study start
- 1 Oct 2019 (actual)
- Primary completion
- 15 Jul 2020 (actual)
- Study completion
- 5 May 2021 (actual)
- First posted
- 18 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CRE infected patients treated with ceftazidime-avibactam | – | Drug: Ceftazidime-AvibactamPatients with infections caused by carbapenem resistant enterobacteria treated with ceftazidime-avibactam |
| CRE infected patients treated with best available treatment | – | Drug: Best Available TherapyPatients with infections caused by carbapenem resistant enterobacteria treated with the best available treatment |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with infections caused by carbapenem resistant enterobacteria
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ceftazidime-AvibactamPatients 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. | Drug | CRE infected patients treated with ceftazidime-avibactam |
| Best Available TherapyPatients 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. | Drug | CRE infected patients treated with best available treatment |
Primary outcome
30-day mortality rate
Time frame: 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
Time frame: 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.
7 secondary outcomes
Microbiological response
Time frame: 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
Time frame: At day 30 after the start of the treatment
Risk factors associated with the development of resistance to ceftazidime-avibactam during treatmen
Time frame: At day 30 after the start of the treatment
Duration of hospital stay after infection
Time frame: At day 30 after the start of the treatment
Duration of antibiotic treatment during the episode
Time frame: At day 30 after the start of the treatment
Recurrence
Time frame: At day 30 after the start of the treatment
Safety evaluation of the treatment
Time frame: At day 30 after the start of the treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2021.
- Individual participant dataSharing planned: Yes. The information collected will be of public access by request.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Juan José Castón Osorio, MD principal investigator
Hospital General Universitario Reina Sofía de Murcia
17 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Carbapenem-Resistant Enterobacteriaceae Infection, run by Maimónides Biomedical Research Institute of Córdoba at 17 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
30-day mortality rate (time frame: At day 30 after the start of the treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jul 2021.