Liver TransplantPhase 3TAILORNCT07759453
Targeted Versus Standard Peri-operative Antibiotic Prophylaxis in Patients Colonized With Carbapenemase Producing Enterobacterales Undergoing Liver Transplantation
A Phase 3 study testing Ceftazidime - Avibactam ( CAZ-AVI), Meropenem-Vaborbactam and Imipenem+Relebactam in people with Liver Transplant and Carbapenem-resistant Enterobacterales, run by IRCCS Azienda Ospedaliero-Universitaria di Bologna at 3 sites in Italy.
Trial summary
This is a multicenter stepped-wedge cluster randomized trial, conducted over a 2-year period at three hospitals. The trial is structured into four phases, each lasting six months. During phase 1 (pre-rollout), all hospitals will use standard antibiotic prophylaxis for all patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Transplant, Carbapenem-resistant Enterobacterales, CRE Colonization
- What is being tested?
- Ceftazidime - Avibactam ( CAZ-AVI), Meropenem-Vaborbactam and Imipenem+Relebactam
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 168 participants
- Where
- 3 sitesItaly
- Study dates
- 1 Oct 2026to 30 Sep 2029
- Phase
- Phase 3
- 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
Who may be able to join
- Adult (≥18 years) patients colonized with Carbapenemase-Producing Enterobacterales (CPE) undergoing liver transplantation (LT)
- Informed consent signed by the enrolled patients
Who cannot join
- Active infection from any Gram-negative bacteria at the time of LT
- High risk of donor-derived CPE infection (e.g., donors known to be colonized or infected with CPE at the time of death, or CPE isolated from donor blood or preservation fluid samples)
- Hypersensitivity to the active substance or to any of the excipients
- Pregnancy and breastfeeding
- Participation in a clinical trial in which an investigational drug was administered within 30 days of screening or within the 5 half-lives of the study drug, whichever is longer.
- History of severe immediate hypersensitivity reactions (e.g., anaphylaxis) to beta-lactam agents (e.g., cephalosporins, carbapenems, or monobactams).
- Colonization by strains resistant to all Investigational Medicinal Products (IMPs)
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Italy3 sites
Irccs Azienda Ospedaliero-Universitaria Di Bologna
Bologna, BO, 40138
Maddalena Giannella, MD, PhD, +39 051 2143199, maddalena.giannella@unibo.it
Matteo Rinaldi, MD, +39 051 2143595, matteo.rinaldi@aosp.bo.it
Azienda Ospedaliero Universitaria Pisana
Pisa, PI, 56126
Marco Falcone, MD, 0039 050 996735, marco.falcone@unipi.it
Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino
Torino, TO, 10126
Silvia Corcione, MD, PhD, +39 0116705466, silvia.corcione@unito.it
About this study
Official title: Targeted Versus Standard Peri-operative Antibiotic Prophylaxis in Patients Colonized With Carbapenemase-producing Enterobacterales Undergoing Liver Transplantation: a Stepped Wedge Cluster Randomization Trial
This is a multicenter stepped-wedge cluster randomized trial, conducted over a 2-year period at three hospitals. The trial is structured into four phases, each lasting six months. During phase 1 (pre-rollout), all hospitals will use standard antibiotic prophylaxis for all patients. In each of phases 2 to 4, one hospital will switch to targeted antibiotic prophylaxis, so that by phase 4 all hospitals will be using it. The order in which hospitals switch is determined by computer-generated randomization performed centrally by an independent statistician, ensuring each hospital has an equal chance of switching at any given phase and minimizing selection bias.
The goal of this clinical trial is to learn whether targeted antibiotic prophylaxis works better than standard antibiotic prophylaxis at preventing infections in liver transplant patients who carry resistant bacteria called CPE (carbapenemase-producing Enterobacterales). It will also learn about the effects of these antibiotics on gut bacteria.
Read more
The main questions it aims to answer are:
- Does targeted antibiotic prophylaxis reduce the number of CPE infections occurring in the first two weeks after liver transplant, compared to standard prophylaxis?
- How do targeted and standard antibiotic prophylaxis affect the gut microbiome after transplant?
- Is there a link between achieving optimal antibiotic blood levels and the risk of developing an infection after transplant?
Researchers will compare targeted antibiotic prophylaxis (chosen based on the specific bacteria each patient carries) to standard antibiotic prophylaxis (used routinely at each hospital) to see which approach better prevents infection.
This study does not involve the administration of any drugs or instrumental examinations beyond those already part of standard clinical care at each center. However, additional blood tests will be performed by collecting one extra blood sample (and a bile sample, if the patient has a Kehr's tube, which is a drain placed in the bile duct after surgery) during blood draws already scheduled as part of routine clinical practice, in order to measure drug levels in the blood. Stool samples will also be collected specifically for the study to investigate the gut microbiome.
Read the detailed description
Colonization and infection with carbapenemase-producing Enterobacterales (CPE) have been associated with significant morbidity and mortality in the setting of solid organ transplantation (SOT), and in particular among liver transplant (LT) candidates and/or recipients. Indeed, the prevalence of CPE infection is highest after LT compared with other types of SOT, CPE carriage is the strongest predisposing factor, and CPE carriage/infection has been associated with significant increase in the odds of death across multiple studies. Several strategies have been proposed to reduce CPE infection and associated poor outcome after LT, including active screening, decolonization and targeted perioperative antibiotic prophylaxis (T-PAP). Decolonization is no longer recommended due to its limited benefit and associated adverse events, observed also in a randomized controlled trial on SOT recipients. Recent European guidelines endorsed the performance of active screening for CPE carriage before LT but, due to the lack of evidence, they could not provide a recommendation regarding optimal PAP in CPE carriers. This study addresses a critical unmet need in liver transplantation by evaluating targeted perioperative antibiotic prophylaxis (T-PAP) versus standard perioperative antibiotic prophylaxis (S-PAP) in CPE colonized patients. By using a stepped-wedge cluster-randomized design, it could generate robust, practice-changing evidence on how to reduce early CPE infections, mortality, and healthcare costs. The project is innovative in study design as well as in integrating advanced gut microbiome (GM) and resistome analyses, offering new insights into the GM effects of perioperative antibiotic strategies. The use of therapeutic drug monitoring (TDM) to optimize dosing adds a precision medicine approach. Findings are expected to impact clinical guidelines and improve outcomes for transplant recipients and potentially for other high-risk surgical populations.
The stepped-wedge design is better suited than standard individual randomization for evaluating the potential indirect effects of the T-PAP policy on gut microbiome and liver functionality.
The intervention will consist of targeted perioperative antibiotic prophylaxis (T-PAP) using an agent shown to be active in vitro against the colonizing strain. The specific drug will be selected at the discretion of the local investigator, in collaboration with the attending physician, and, if necessary, discussed with all the study investigators in a dedicated meeting. In the control arm, standard perioperative antibiotic prophylaxis (S-PAP) will be administered according to local protocols. In both arms, prophylaxis will begin 30-60 minutes before surgical incision, following guidelines, and will be discontinued no later than 48 hours post-surgery.
- Being tested
- Ceftazidime - Avibactam ( CAZ-AVI), Meropenem-Vaborbactam, Imipenem+Relebactam, Cefiderocol, Aztreonam
- Keywords
- CRE colonization, liver transplant, stepped-wedge cluster randomized trial, therapeutic drug monitoring, gut microbiome, carbapenem-resistant enterobacterales
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ceftazidime - Avibactam ( CAZ-AVI)Drug
2g/0.5g powder for concentrate for solution for infusion.Each vial contains ceftazidime pentahydrate equivalent to 2 g ceftazidime and avibactam sodium equivalent to 0.5 g avibactam. For T-PAP, the administration should not exceed 48 hours
Meropenem-VaborbactamDrug
1g/1g powder for concentrate for solution for infusion. Each vial contains meropenem trihydrate equivalent to 1 g meropenem, and 1 g vaborbactam. Excipient with known effect: Each vial contains 10.9 mmol of sodium (approximately 250 mg). For T-PAP, the administration should not exceed 48 hours.
Imipenem+RelebactamDrug
Supplied as a dry powder in a single-dose vial that must be constituted and further diluted using aseptic technique prior to intravenous infusion (IV).
Each vial contains imipenem monohydrate equivalent to 500 mg imipenem, cilastatin sodium equivalent to 500 mg cilastatin, and relebactam monohydrate equivalent to 250 mg relebactam. For T-PAP, the administration should not exceed 48 hours.
CefiderocolDrug
Supplied as single use vials containing cefiderocol sodium tosylate, equivalent to 1 g cefiderocol. Excipients include sucrose, sodium chloride and sodium hydroxide. For T-PAP, the administration should not exceed 48 hours.
AztreonamDrug
Supplied as a single use vials containing sterile solution of Aztreonam and Arginine and a suitable osmolality adjusting substance in Water for Injection. It contains NLT 90.0% and NMT 120.0% of the labeled amount of aztreonam. For T-PAP, the administration should not exceed 48 hours.
EravacyclineDrug
Supplied as powder for concentrate for solution for infusion, each vial contains 50 mg of eravacycline. Each vial is for single use only, that must be reconstituted and further diluted using aseptic technique prior to intravenous infusion. For T-PAP, the administration should not exceed 48 hours.
Aztreonam-AvibactamDrug
Supplied as powder for concentrate for solution for infusion, each vial contains 1.5 g of aztreonam and avibactam sodium equivalent to 0.5 g of avibactam. For T-PAP, the administration should not exceed 48 hours.
Amoxi ClavulanateDrug
Powder for solution for injection or infusion, supplied as vials of 2000/200 mg. Each vial contains 2000 mg amoxicillin (as amoxicillin sodium) and 200 mg clavulanic acid (as potassium clavulanate). Each vial contains 5.5 mmol (125.9 mg) of sodium and 1 mmol (39.3 mg) of potassium. For S-PAP, the duration should not exceed 48 hours.
Piperacillin + TazobactamDrug
Powder for solution, each vial contains amounts of Piperacillin Sodium and Tazobactam Sodium equivalent to not less than 90.0 percent and not more than 110.0 percent of the labeled amounts of piperacillin, the labeled amounts representing proportions of piperacillin to tazobactam is of 8 : 1. It may contain small amounts of a suitable buffer stabilizer. For S-PAP, the duration should not exceed 48 hours.
TigecyclineDrug
Powder for solution, each vial should be reconstituted with 5.3 mL of 0.9% Sodium Chloride Injection, or 5% Dextrose Injection, to achieve a concentration of 10 mg/mL of tigecycline. For S-PAP, the duration should not exceed 48 hours.
| Study group | Role | What they receive |
|---|---|---|
| Targeted prophylaxis T-PAP | Experimental | Patients included in the Targeted prophylaxis (T-PAP) arm will be treated using an agent shown to be active in vitro against the colonizing strain. The specific drug will be selected at the discretion of the local investigator, in collaboration with the attending physician, and, if necessary, discussed with all the study investigators in a dedicated meeting.All drugs will be used strictly in accordance with their approved Summary of Product Characteristics (SmPC).
Available drugs that could be used as a T-PAP are:
* Ceftazidime/avibactam
* Meropenem/vaborbactam
* Imipenem/relebactam
* Cefiderocol
* Aztreonam
* Eravacycline
* Aztreonam/avibactam Receives: Drug: Ceftazidime - Avibactam ( CAZ-AVI); Drug: Meropenem-Vaborbactam; Drug: Imipenem+Relebactam; Drug: Cefiderocol; Drug: Aztreonam; Drug: Eravacycline; Drug: Aztreonam-Avibactam |
| Standard prophylaxis S-PAP | Experimental | Patients include in the Standard prophylaxis (S-PAP) arm will be treated with standard drugs administered according to local protocols.
Drugs used as S-PAP are:
* Amoxicillin/clavulanate
* Piperacillin/tazobactam
* Tigecycline Receives: Drug: Amoxi Clavulanate; Drug: Piperacillin + Tazobactam; Drug: Tigecycline |
What is being measured
The primary outcome is the main question the study is designed to answer.
To investigate the impact of T-PAP vs. S-PAP on the incidence of early CPE infection after LT in patients colonized with CPE undergoing LT
The impact of T-PAP over S-PAP will be calculated comparing the percentage of CPE infections in the first two weeks after LT in the intervention and control group.
Measured: Within 14 days after liver transplant
Secondary outcomes (6)
To investigate the impact of T-PAP vs. S-PAP on the dynamics of gut microbiome after LT in patients colonized with CPE at transplant
Cross-sectional differences between T-PAP and S-PAP groups over time, in GM alpha diversity, composition (relative abundance at different taxonomic levels) and functionality (gene and pathway abundances), will be assessed using the Kruskal-Wallis test, followed by post-hoc Wilcoxon rank-sum tests.
Measured: At the time of liver transplant, and at 14, 30, 60 and 90 days after liver transplant
To investigate the relationship between the attainment of optimal pharmacokinetics/pharmacodynamics (PK/PD) target and the occurrence of CPE and non-CPE infections after LT in patients colonized with CPE at transplant
In order to evaluate the relationship between the attainment of early optimal PK/PD target with agents used for both T-PAP and S-PAP and the occurrence of CPE and non-CPE infections in the post-LT period, TDM of selected agents will be performed at the end of surgical procedure and at 24 hours after starting T-PAP and S-PAP. The relationship between the attainment of optimal PK/PD target and the occurrence of CPE and non-CPE infections will be calculated comparing the percentage of patients developing CPE and non-CPE infections in the first two weeks after LT in the intervention and control group.
Measured: Within 14 days from liver transplant
To investigate the impact of T-PAP vs. S-PAP on CPE carriage status
The impact of T-PAP vs S-PAP on CPE carriage status will be calculated comparing the percentage of patients colonized with Carbapenem-producing Enterobacterales (CPE) at 30, 60 and 90 days after LT in the intervention and control group.
Measured: At 30, 60 and 90 days after liver transplant
To investigate the development of bacterial infections
The impact of T-PAP vs S-PAP will be calculated comparing the percentage of patients diagnosed with a bacterial infection at 30, 60 and 90 days after LT in the intervention and control group.
Measured: At 30, 60 and 90 days after liver transplant
To investigate all-cause mortality
The impact of T-PAP vs S-PAP will be calculated comparing the percentage of patients who died from any cause at 30, 60 and 90 days after LT in the intervention and control group.
Measured: At 30, 60 and 90 days after liver transplant
To investigate the safety of T-PAP versus S-PAP
The rates of adverse events (e.g. neurotoxicity) in the intervention and in the control groups will be computed.
Measured: During prophylaxis administration or within 7 days from the initiation of administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2026
- Study start1 Oct 2026 (estimated)
- Primary completion30 Jun 2029 (estimated)
- Study completion30 Sep 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver TransplantStudies 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
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- A stepped-wedge cluster randomized trial will be conducted over a 2-year period at three hospitals. The trial will be structured into four phases, each lasting six months. During phase 1 (pre-rollout), all clusters (i.e. hospitals) will use S-PAP for all patients. In each of the phases 2 to 4 one cluster will transition to T-PAP, so that in phase 4 all clusters will use T-PAP. Cluster transitions from S-PAP to T-PAP will be determined by centrally performed computer generated randomization by an independent statistician, ensuring equal probability of assignment and minimizing selection bias. The randomization sequence will be generated prior to study initiation and kept confidential until implementation.
- Masking
- None (open label)
- Enrolment
- 168 participants (estimated)
Sponsor and investigators
- Lead sponsor
- IRCCS Azienda Ospedaliero-Universitaria di Bologna
- 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
- NCT07759453
- Sponsor's protocol ID
- TAILOR
- Other IDs
- 2025-523453-34-00, 2025
- Acronym
- TAILOR
- Status last verified
- Jun 2026
- First submitted
- 19 Jun 2026
- Last updated
- 12 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Targeted Versus Standard Peri-operative Antibiotic Prophylaxis in Patients Colonized With Carbapenemase-producing Enterobacterales Undergoing Liver Transplantation: a Stepped Wedge Cluster Randomization Trial
- ClinicalTrials.gov ID
- NCT07759453
- Acronym / sponsor ID
- TAILOR / TAILOR
- Keywords
- CRE colonization, liver transplant, stepped-wedge cluster randomized trial, therapeutic drug monitoring, gut microbiome, carbapenem-resistant enterobacterales
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 168 participants (estimated)
- Lead sponsor
- IRCCS Azienda Ospedaliero-Universitaria di BolognaUniversity, hospital or other
- Study start
- 1 Oct 2026 (estimated)
- Primary completion
- 30 Jun 2029 (estimated)
- Study completion
- 30 Sep 2029 (estimated)
- First posted
- 12 Aug 2026 (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.
This is a multicenter stepped-wedge cluster randomized trial, conducted over a 2-year period at three hospitals. The trial is structured into four phases, each lasting six months. During phase 1 (pre-rollout), all hospitals will use standard antibiotic prophylaxis for all patients. In each of phases 2 to 4, one hospital will switch to targeted antibiotic prophylaxis, so that by phase 4 all hospitals will be using it. The order in which hospitals switch is determined by computer-generated randomization performed centrally by an independent statistician, ensuring each hospital has an equal chance of switching at any given phase and minimizing selection bias.
The goal of this clinical trial is to learn whether targeted antibiotic prophylaxis works better than standard antibiotic prophylaxis at preventing infections in liver transplant patients who carry resistant bacteria called CPE (carbapenemase-producing Enterobacterales). It will also learn about the effects of these antibiotics on gut bacteria.
The main questions it aims to answer are:
- Does targeted antibiotic prophylaxis reduce the number of CPE infections occurring in the first two weeks after liver transplant, compared to standard prophylaxis?
- How do targeted and standard antibiotic prophylaxis affect the gut microbiome after transplant?
- Is there a link between achieving optimal antibiotic blood levels and the risk of developing an infection after transplant?
Researchers will compare targeted antibiotic prophylaxis (chosen based on the specific bacteria each patient carries) to standard antibiotic prophylaxis (used routinely at each hospital) to see which approach better prevents infection.
This study does not involve the administration of any drugs or instrumental examinations beyond those already part of standard clinical care at each center. However, additional blood tests will be performed by collecting one extra blood sample (and a bile sample, if the patient has a Kehr's tube, which is a drain placed in the bile duct after surgery) during blood draws already scheduled as part of routine clinical practice, in order to measure drug levels in the blood. Stool samples will also be collected specifically for the study to investigate the gut microbiome.
Detailed description
Colonization and infection with carbapenemase-producing Enterobacterales (CPE) have been associated with significant morbidity and mortality in the setting of solid organ transplantation (SOT), and in particular among liver transplant (LT) candidates and/or recipients. Indeed, the prevalence of CPE infection is highest after LT compared with other types of SOT, CPE carriage is the strongest predisposing factor, and CPE carriage/infection has been associated with significant increase in the odds of death across multiple studies. Several strategies have been proposed to reduce CPE infection and associated poor outcome after LT, including active screening, decolonization and targeted perioperative antibiotic prophylaxis (T-PAP). Decolonization is no longer recommended due to its limited benefit and associated adverse events, observed also in a randomized controlled trial on SOT recipients. Recent European guidelines endorsed the performance of active screening for CPE carriage before LT but, due to the lack of evidence, they could not provide a recommendation regarding optimal PAP in CPE carriers. This study addresses a critical unmet need in liver transplantation by evaluating targeted perioperative antibiotic prophylaxis (T-PAP) versus standard perioperative antibiotic prophylaxis (S-PAP) in CPE colonized patients. By using a stepped-wedge cluster-randomized design, it could generate robust, practice-changing evidence on how to reduce early CPE infections, mortality, and healthcare costs. The project is innovative in study design as well as in integrating advanced gut microbiome (GM) and resistome analyses, offering new insights into the GM effects of perioperative antibiotic strategies. The use of therapeutic drug monitoring (TDM) to optimize dosing adds a precision medicine approach. Findings are expected to impact clinical guidelines and improve outcomes for transplant recipients and potentially for other high-risk surgical populations.
The stepped-wedge design is better suited than standard individual randomization for evaluating the potential indirect effects of the T-PAP policy on gut microbiome and liver functionality.
The intervention will consist of targeted perioperative antibiotic prophylaxis (T-PAP) using an agent shown to be active in vitro against the colonizing strain. The specific drug will be selected at the discretion of the local investigator, in collaboration with the attending physician, and, if necessary, discussed with all the study investigators in a dedicated meeting. In the control arm, standard perioperative antibiotic prophylaxis (S-PAP) will be administered according to local protocols. In both arms, prophylaxis will begin 30-60 minutes before surgical incision, following guidelines, and will be discontinued no later than 48 hours post-surgery.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- A stepped-wedge cluster randomized trial will be conducted over a 2-year period at three hospitals. The trial will be structured into four phases, each lasting six months. During phase 1 (pre-rollout), all clusters (i.e. hospitals) will use S-PAP for all patients. In each of the phases 2 to 4 one cluster will transition to T-PAP, so that in phase 4 all clusters will use T-PAP. Cluster transitions from S-PAP to T-PAP will be determined by centrally performed computer generated randomization by an independent statistician, ensuring equal probability of assignment and minimizing selection bias. The randomization sequence will be generated prior to study initiation and kept confidential until implementation.
| Arm | Type | Receives |
|---|---|---|
| Targeted prophylaxis T-PAP | Experimental | Drug: Ceftazidime - Avibactam ( CAZ-AVI), Drug: Meropenem-Vaborbactam, Drug: Imipenem+Relebactam, Drug: Cefiderocol, Drug: Aztreonam, Drug: Eravacycline, Drug: Aztreonam-AvibactamPatients included in the Targeted prophylaxis (T-PAP) arm will be treated using an agent shown to be active in vitro against the colonizing strain. The specific drug will be selected at the discretion of the local investigator, in collaboration with the attending physician, and, if necessary, discussed with all the study investigators in a dedicated meeting.All drugs will be used strictly in accordance with their approved Summary of Product Characteristics (SmPC). Available drugs that could be used as a T-PAP are: * Ceftazidime/avibactam * Meropenem/vaborbactam * Imipenem/relebactam * Cefiderocol * Aztreonam * Eravacycline * Aztreonam/avibactam |
| Standard prophylaxis S-PAP | Experimental | Drug: Amoxi Clavulanate, Drug: Piperacillin + Tazobactam, Drug: TigecyclinePatients include in the Standard prophylaxis (S-PAP) arm will be treated with standard drugs administered according to local protocols. Drugs used as S-PAP are: * Amoxicillin/clavulanate * Piperacillin/tazobactam * Tigecycline |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Adult (≥18 years) patients colonized with Carbapenemase-Producing Enterobacterales (CPE) undergoing liver transplantation (LT)
- Informed consent signed by the enrolled patients
Key exclusion criteria (7 listed)
- Active infection from any Gram-negative bacteria at the time of LT
- High risk of donor-derived CPE infection (e.g., donors known to be colonized or infected with CPE at the time of death, or CPE isolated from donor blood or preservation fluid samples)
- Hypersensitivity to the active substance or to any of the excipients
- Pregnancy and breastfeeding
- Participation in a clinical trial in which an investigational drug was administered within 30 days of screening or within the 5 half-lives of the study drug, whichever is longer.
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 - Avibactam ( CAZ-AVI)2g/0.5g powder for concentrate for solution for infusion.Each vial contains ceftazidime pentahydrate equivalent to 2 g ceftazidime and avibactam sodium equivalent to 0.5 g avibactam. For T-PAP, the administration should not exceed 48 hours | Drug | Targeted prophylaxis T-PAP |
| Meropenem-Vaborbactam1g/1g powder for concentrate for solution for infusion. Each vial contains meropenem trihydrate equivalent to 1 g meropenem, and 1 g vaborbactam. Excipient with known effect: Each vial contains 10.9 mmol of sodium (approximately 250 mg). For T-PAP, the administration should not exceed 48 hours. | Drug | Targeted prophylaxis T-PAP |
| Imipenem+RelebactamSupplied as a dry powder in a single-dose vial that must be constituted and further diluted using aseptic technique prior to intravenous infusion (IV). Each vial contains imipenem monohydrate equivalent to 500 mg imipenem, cilastatin sodium equivalent to 500 mg cilastatin, and relebactam monohydrate equivalent to 250 mg relebactam. For T-PAP, the administration should not exceed 48 hours. | Drug | Targeted prophylaxis T-PAP |
| CefiderocolSupplied as single use vials containing cefiderocol sodium tosylate, equivalent to 1 g cefiderocol. Excipients include sucrose, sodium chloride and sodium hydroxide. For T-PAP, the administration should not exceed 48 hours. | Drug | Targeted prophylaxis T-PAP |
| AztreonamSupplied as a single use vials containing sterile solution of Aztreonam and Arginine and a suitable osmolality adjusting substance in Water for Injection. It contains NLT 90.0% and NMT 120.0% of the labeled amount of aztreonam. For T-PAP, the administration should not exceed 48 hours. | Drug | Targeted prophylaxis T-PAP |
| EravacyclineSupplied as powder for concentrate for solution for infusion, each vial contains 50 mg of eravacycline. Each vial is for single use only, that must be reconstituted and further diluted using aseptic technique prior to intravenous infusion. For T-PAP, the administration should not exceed 48 hours. | Drug | Targeted prophylaxis T-PAP |
| Aztreonam-AvibactamSupplied as powder for concentrate for solution for infusion, each vial contains 1.5 g of aztreonam and avibactam sodium equivalent to 0.5 g of avibactam. For T-PAP, the administration should not exceed 48 hours. | Drug | Targeted prophylaxis T-PAP |
| Amoxi ClavulanatePowder for solution for injection or infusion, supplied as vials of 2000/200 mg. Each vial contains 2000 mg amoxicillin (as amoxicillin sodium) and 200 mg clavulanic acid (as potassium clavulanate). Each vial contains 5.5 mmol (125.9 mg) of sodium and 1 mmol (39.3 mg) of potassium. For S-PAP, the duration should not exceed 48 hours. | Drug | Standard prophylaxis S-PAP |
| Piperacillin + TazobactamPowder for solution, each vial contains amounts of Piperacillin Sodium and Tazobactam Sodium equivalent to not less than 90.0 percent and not more than 110.0 percent of the labeled amounts of piperacillin, the labeled amounts representing proportions of piperacillin to tazobactam is of 8 : 1. It may contain small amounts of a suitable buffer stabilizer. For S-PAP, the duration should not exceed 48 hours. | Drug | Standard prophylaxis S-PAP |
| TigecyclinePowder for solution, each vial should be reconstituted with 5.3 mL of 0.9% Sodium Chloride Injection, or 5% Dextrose Injection, to achieve a concentration of 10 mg/mL of tigecycline. For S-PAP, the duration should not exceed 48 hours. | Drug | Standard prophylaxis S-PAP |
Primary outcome
To investigate the impact of T-PAP vs. S-PAP on the incidence of early CPE infection after LT in patients colonized with CPE undergoing LT
Time frame: Within 14 days after liver transplant
The impact of T-PAP over S-PAP will be calculated comparing the percentage of CPE infections in the first two weeks after LT in the intervention and control group.
6 secondary outcomes
To investigate the impact of T-PAP vs. S-PAP on the dynamics of gut microbiome after LT in patients colonized with CPE at transplant
Time frame: At the time of liver transplant, and at 14, 30, 60 and 90 days after liver transplant
To investigate the relationship between the attainment of optimal pharmacokinetics/pharmacodynamics (PK/PD) target and the occurrence of CPE and non-CPE infections after LT in patients colonized with CPE at transplant
Time frame: Within 14 days from liver transplant
To investigate the impact of T-PAP vs. S-PAP on CPE carriage status
Time frame: At 30, 60 and 90 days after liver transplant
To investigate the development of bacterial infections
Time frame: At 30, 60 and 90 days after liver transplant
To investigate all-cause mortality
Time frame: At 30, 60 and 90 days after liver transplant
To investigate the safety of T-PAP versus S-PAP
Time frame: During prophylaxis administration or within 7 days from the initiation of administration
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 Aug 2026.
- Individual participant dataSharing planned: No
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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.
Maddalena Giannella, MD, PhD principal investigator
IRCCS Azienda Ospedaliero-Universitaria di Bologna
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ceftazidime - Avibactam ( CAZ-AVI), Meropenem-Vaborbactam and Imipenem+Relebactam in people with Liver Transplant and Carbapenem-resistant Enterobacterales, run by IRCCS Azienda Ospedaliero-Universitaria di Bologna at 3 sites in Italy.
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 7 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: opening soon, as of the sponsor's last update on 12 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Italy. 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 (+39 051 2143199, maddalena.giannella@unibo.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To investigate the impact of T-PAP vs. S-PAP on the incidence of early CPE infection after LT in patients colonized with CPE undergoing LT (time frame: Within 14 days after liver transplant). 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 Aug 2026; AzTrials last refreshed its copy on 26 Oct 2026.