Gram Negative InfectionsCAVIFOSNCT06717594
PK/PD Relationship of CAZ/AVI and FOS in the Treatment of Patients With Infections Due to CRE
An observational study of Gram Negative Infections and Antimicrobial Resistance (AMR), run by IRCCS Azienda Ospedaliero-Universitaria di Bologna at 2 sites in 2 countries.
Trial summary
A multicenter international prospective observational pharmacological study in adult patients (≥18 years) treated with ceftazidime/avibactam (CAZ/AVI) alone or with CAZ/AVI plus fosfomycin (FOS) for infection due to carbapenem-resistant Enterobacterales (CRE) (KPC and/or OXA-48). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gram Negative Infections, Antimicrobial Resistance (AMR)
- How many people
- 60 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 1 Dec 2023to 31 Dec 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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: Adult patients with infection due to a difficult-to-treat Gram-negative bacteria, treated with CAZ/AVI alone or CAZ/AVI plus FOS, hospitalized during the study period in the participating centers, will be screened for inclusion
Who may be able to join
- Signature of the informed consent
- Age ≥ 18 years
- Adult patients treated for ≥ 48 hours with CAZ/AVI or CAZ/AVI plus FOS for a microbiologically documented CRE infection
Who cannot join
- Polymicrobial/mixed infections with exception of cases with multiple Enterobacterales susceptible to study drugs
Trial locations and contacts
2 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
2 sites in 2 countries
Italy1 site, 1 recruiting
- Recruiting
IRCCS Azienda Ospedaliero-Universitaria di Bologna
Bologna, Bologna, 40138
Maddalena Giannella, MD PhD, +390512143199, maddalena.giannella@unibo.it
Spain1 site, 1 recruiting
- Recruiting
Instituto de Biomedicina de Sevilla (IBiS), Hospital Virgen Macarena/CSIC/Universidad de Sevilla
Seville, Seville, 41013
Fernando M Docobo Pérez, PhD, +34 954118805, fdocobo1@us.es
About this study
Official title: PK/PD Relationship of CAZ/AVI and FOS in the Treatment of Patients With Infections Due to Carbapenem-resistant Enterobacterales (CRE)
A multicenter international prospective observational pharmacological study in adult patients (≥18 years) treated with ceftazidime/avibactam (CAZ/AVI) alone or with CAZ/AVI plus fosfomycin (FOS) for infection due to carbapenem-resistant Enterobacterales (CRE) (KPC and/or OXA-48).
Read the detailed description
Gram-negative infections, particularly those caused by carbapenem-resistant Enterobacterales (CRE), have a dramatic impact on patient survival. Despite the introduction of new drugs in the last years have improved the outcome of patients with CRE infections, mortality and relapse rates are still relevant, especially in patients with high-risk source as pneumonia, and those in which the attainment of optimal exposure could be reduced by underlying renal disease. The use of combination regimen in these scenarios has been proposed. However, a standardized approach is still missing. Since several in vitro studies have highlighted the synergistic effect of fosfomycin (FOS) with different antibiotic classes, including cephalosporins such drug could be an appealing option in combination therapy for the management of CRE infections.
In particular, the primary aim of the study is to assess the probability of achieving a pre-defined target of efficacy in patients treated with ceftazidime/avibactam (CAZ/AVI) and/or FOS according to different modes of drug administration in patients with CRE infections.
Secondary aim is to assess the association between plasma drug concentration of both CAZ/AVI and FOS and patient response.
- Keywords
- Gram negative infection, Ceftazidime/Avibactam, Fosfomycin, Pharmacokinetics/Pharmacodynamics targets, Carbapenem-resistant Enterobacterales (CRE)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Patients with Carbapenem-resistant Enterobacterales (CRE) infection treated with CAZ/AVI ± FOS | Adult patients treated for ≥ 48 hours with CAZ/AVI or CAZ/AVI plus FOS for a microbiologically documented CRE infection |
What is being measured
The primary outcome is the main question the study is designed to answer.
PK/PD efficacy targets for study drugs
The primary endpoint will be the attainment of the pre-defined PK/PD target of efficacy at 48 and 72 hours after starting treatment for Carbapenem-resistant Enterobacterales (CRE) infection
Measured: From enrollment (treatment onset) to 48 and 72 hours after starting treatment
Secondary outcomes (5)
Difference in SOFA score
Difference in SOFA score between day 0 (day of treatment onset) and day 7
Measured: From day 0 (day of index positive culture) and day 7
Trend of C-Reactive Protein (CRP) and Procalcitonin (PCT)
Trend of C-Reactive Protein (CRP) and Procalcitonin (PCT) from day 0 to day 7 after treatment onset
Measured: From day 0 (day of index positive culture) and day 7
Microbiological eradication
Microbiological eradication defined as bacteraemia clearance or negativization of index diagnostic sample within 7 days from treatment onset
Measured: From day 0 (day of index positive culture) and day 7
Relapse and/or reinfection
Relapse (new infection with the same pathogen emerging after treatment) and/or reinfection (new infection with a different pathogen emerging after treatment) rates at day 90
Measured: From enrollment to the end of the follow-up at three months
All-cause mortality
All-cause mortality at day 30 and at day 90
Measured: From enrollment to the end of the follow-up at three months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2024
- Study start1 Dec 2023
- Primary completion30 Sep 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gram Negative InfectionsStudies of the same condition, open and under way.
- More trials run by IRCCS Azienda Ospedaliero-Universitaria di BolognaThe sponsor's other registered studies.
- 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
- Prospective
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Maddalena Giannella, MD PhD, Principal investigator, IRCCS Azienda Ospedaliero-Universitaria di Bologna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06717594
- Sponsor's protocol ID
- CAVIFOS
- Other IDs
- JPIAMR-ACTION
- Acronym
- CAVIFOS
- Status last verified
- Jun 2026
- First submitted
- 1 Dec 2024
- Last updated
- 12 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PK/PD Relationship of CAZ/AVI and FOS in the Treatment of Patients With Infections Due to Carbapenem-resistant Enterobacterales (CRE)
- ClinicalTrials.gov ID
- NCT06717594
- Acronym / sponsor ID
- CAVIFOS / CAVIFOS
- Keywords
- Gram negative infection, Ceftazidime/Avibactam, Fosfomycin, Pharmacokinetics/Pharmacodynamics targets, Carbapenem-resistant Enterobacterales (CRE)
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- IRCCS Azienda Ospedaliero-Universitaria di BolognaUniversity, hospital or other
- Study start
- 1 Dec 2023 (actual)
- Primary completion
- 30 Sep 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 5 Dec 2024 (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.
A multicenter international prospective observational pharmacological study in adult patients (≥18 years) treated with ceftazidime/avibactam (CAZ/AVI) alone or with CAZ/AVI plus fosfomycin (FOS) for infection due to carbapenem-resistant Enterobacterales (CRE) (KPC and/or OXA-48).
Detailed description
Gram-negative infections, particularly those caused by carbapenem-resistant Enterobacterales (CRE), have a dramatic impact on patient survival. Despite the introduction of new drugs in the last years have improved the outcome of patients with CRE infections, mortality and relapse rates are still relevant, especially in patients with high-risk source as pneumonia, and those in which the attainment of optimal exposure could be reduced by underlying renal disease. The use of combination regimen in these scenarios has been proposed. However, a standardized approach is still missing. Since several in vitro studies have highlighted the synergistic effect of fosfomycin (FOS) with different antibiotic classes, including cephalosporins such drug could be an appealing option in combination therapy for the management of CRE infections.
In particular, the primary aim of the study is to assess the probability of achieving a pre-defined target of efficacy in patients treated with ceftazidime/avibactam (CAZ/AVI) and/or FOS according to different modes of drug administration in patients with CRE infections.
Secondary aim is to assess the association between plasma drug concentration of both CAZ/AVI and FOS and patient response.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with Carbapenem-resistant Enterobacterales (CRE) infection treated with CAZ/AVI ± FOS | – | –Adult patients treated for ≥ 48 hours with CAZ/AVI or CAZ/AVI plus FOS for a microbiologically documented CRE infection |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Adult patients with infection due to a difficult-to-treat Gram-negative bacteria, treated with CAZ/AVI alone or CAZ/AVI plus FOS, hospitalized during the study period in the participating centers, will be screened for inclusion
Key inclusion criteria (3 listed)
- Signature of the informed consent
- Age ≥ 18 years
- Adult patients treated for ≥ 48 hours with CAZ/AVI or CAZ/AVI plus FOS for a microbiologically documented CRE infection
Key exclusion criteria (1 listed)
- Polymicrobial/mixed infections with exception of cases with multiple Enterobacterales susceptible to study drugs
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
PK/PD efficacy targets for study drugs
Time frame: From enrollment (treatment onset) to 48 and 72 hours after starting treatment
The primary endpoint will be the attainment of the pre-defined PK/PD target of efficacy at 48 and 72 hours after starting treatment for Carbapenem-resistant Enterobacterales (CRE) infection
5 secondary outcomes
Difference in SOFA score
Time frame: From day 0 (day of index positive culture) and day 7
Trend of C-Reactive Protein (CRP) and Procalcitonin (PCT)
Time frame: From day 0 (day of index positive culture) and day 7
Microbiological eradication
Time frame: From day 0 (day of index positive culture) and day 7
Relapse and/or reinfection
Time frame: From enrollment to the end of the follow-up at three months
All-cause mortality
Time frame: From enrollment to the end of the follow-up at three months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2026.
Related trials for Gram Negative Infections
RecruitingObservational study
Natural History of Trisomy 8-Associated Autoinflammatory Disease (TRIAD) and Related Disorders
Trisomy 8 Mosaicism, Trisomy 8 Associated Autoinflammatory Disease
RecruitingPhase 3
Keverprazan-Minocycline Dual Therapy of Different Durations Versus Bismuth Quadruple Therapy for Helicobacter Pylori Eradication.
Helicobacter Infection
RecruitingObservational study
Evaluation, Treatment, and Follow-up of Patients With Lyme Disease
Lyme Disease
Not yet recruitingObservational study
Ex Vivo Study of Leukocyte Responses in the Blood of Patients With Leptospirosis and ex Vivo Testing of a New Host-targeted Therapeutic Strategy to Restore Phagocytosis of Leptospira
Leptospirosis, Jarisch Herxheimer Reaction
RecruitingPhase 1
Phase 1 Study of Chlamydia Trachomatis mRNA Vaccine in Adults.
Chlamydia Trachomatis Immunization
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.
Maddalena Giannella, MD PhD principal investigator
IRCCS Azienda Ospedaliero-Universitaria di Bologna
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Gram Negative Infections and Antimicrobial Resistance (AMR), run by IRCCS Azienda Ospedaliero-Universitaria di Bologna at 2 sites in 2 countries.
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 3 inclusion and 1 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: looking for participants now, as of the sponsor's last update on 12 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy, 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Maddalena Giannella, MD PhD (+390512143199, maddalena.giannella@unibo.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PK/PD efficacy targets for study drugs (time frame: From enrollment (treatment onset) to 48 and 72 hours after starting treatment). 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 12 Jun 2026.