Cette page a été traduite automatiquement et l'exactitude de la traduction n'est pas garantie. Veuillez vous référer au version anglaise pour un texte source.

Targeted Versus Standard Peri-operative Antibiotic Prophylaxis in Patients Colonized With Carbapenemase Producing Enterobacterales Undergoing Liver Transplantation (TAILOR)

6 août 2026 mis à jour par: IRCCS Azienda Ospedaliero-Universitaria di Bologna

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.

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.

Aperçu de l'étude

Statut

Pas encore de recrutement

Les conditions

Intervention / Traitement

Description détaillée

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.

Type d'étude

Interventionnel

Inscription (Estimé)

168

Phase

  • Phase 3

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Coordonnées de l'étude

Sauvegarde des contacts de l'étude

Lieux d'étude

  • Italie
    • BO
      • Bologna, BO, Italie, 40138
        • IRCCS Azienda Ospedaliero-Universitaria di Bologna
        • Contact:
        • Contact:
        • Sous-enquêteur:
          • Matteo Rinaldi, MD
    • PI
      • Pisa, PI, Italie, 56126
        • Azienda Ospedaliero Universitaria Pisana
        • Contact:
    • TO
      • Torino, TO, Italie, 10126
        • Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino
        • Contact:

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

  • Adulte
  • Adulte plus âgé

Accepte les volontaires sains

Non

La description

Inclusion Criteria:

  • Adult (≥18 years) patients colonized with Carbapenemase-Producing Enterobacterales (CPE) undergoing liver transplantation (LT)
  • Informed consent signed by the enrolled patients

Exclusion Criteria:

  • 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)

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation croisée
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: Targeted prophylaxis T-PAP

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
Médicament: 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
Médicament: Meropenem-Vaborbactam
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.
Médicament: Imipenem+Relebactam

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.

Médicament: Cefiderocol
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.
Médicament: Aztreonam
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.
Médicament: Eravacycline
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.
Médicament: Aztreonam-Avibactam
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.
Expérimental: Standard prophylaxis S-PAP

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
Médicament: Amoxi Clavulanate
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.
Médicament: Piperacillin + Tazobactam
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.
Médicament: Tigecycline
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.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
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
Délai: 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.
Within 14 days after liver transplant

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
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
Délai: At the time of liver transplant, and at 14, 30, 60 and 90 days after liver 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.
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
Délai: Within 14 days from liver 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.
Within 14 days from liver transplant
To investigate the impact of T-PAP vs. S-PAP on CPE carriage status
Délai: At 30, 60 and 90 days after liver transplant
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.
At 30, 60 and 90 days after liver transplant
To investigate the development of bacterial infections
Délai: At 30, 60 and 90 days after liver transplant
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.
At 30, 60 and 90 days after liver transplant
To investigate all-cause mortality
Délai: At 30, 60 and 90 days after liver transplant
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.
At 30, 60 and 90 days after liver transplant
To investigate the safety of T-PAP versus S-PAP
Délai: During prophylaxis administration or within 7 days from the initiation of administration
The rates of adverse events (e.g. neurotoxicity) in the intervention and in the control groups will be computed.
During prophylaxis administration or within 7 days from the initiation of administration

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

IRCCS Azienda Ospedaliero-Universitaria di Bologna

Les enquêteurs

  • Chercheur principal: Maddalena Giannella, MD, PhD, IRCCS Azienda Ospedaliero-Universitaria di Bologna

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Estimé)

1 octobre 2026

Achèvement primaire (Estimé)

30 juin 2029

Achèvement de l'étude (Estimé)

30 septembre 2029

Dates d'inscription aux études

Première soumission

19 juin 2026

Première soumission répondant aux critères de contrôle qualité

6 août 2026

Première publication (Réel)

12 août 2026

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

12 août 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

6 août 2026

Dernière vérification

1 juin 2026

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • TAILOR
  • 2025-523453-34-00 (Ctis)

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

NON

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Non

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

S'abonner