Prophylaxie par la rézafungine en cas de transplantation hépatique
Prophylaxie par la rézafungine lors d'une transplantation hépatique à haut risque d'infection fongique invasive
This is an interventional study to evaluate the efficacy of rezafungin, a new echinocandin, for the prevention of invasive fungal infections (IFIs) after liver transplantation. Patients who receive rezafungin will be compared to a similar group of patients who underwent liver transplantation in the preceding two years for the incidence of IFIs.
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
This is a single arm interventional study of consecutive liver transplant recipients who have consented to this rezafungin prophylaxis study. The outcome will be compared with that of similar group of patients not enrolled in the study and those who underwent liver transplant in the preceding two years (historical controls). Propensity score matching will be used to select retrospective cohort.
There will be 3 groups:
- Study group (prospective intervention cohort): Rezafungin (180 patients)
- Prospective control group (prospective control cohort): Patients who receive fluconazole/voriconazole or no antifungal prophylaxis as part of UPMC's tiered antifungal prophylaxis standard of care (20 patients: 10 who receive fluconazole/voriconazole and 10 who do not receive fluconazole/voriconazole)
- Historical control group (retrospective control cohort): Patients at risk for IFI who received fluconazole/voriconazole (tier approach) in the two years preceding this study (180 patients)
Type d'étude
Inscription (Estimé)
Phase
- Phase 3
Contacts et emplacements
Lieux d'étude
-
-
Pennsylvania
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Pittsburgh, Pennsylvania, États-Unis, 15213
- UPMC Presbyterian
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-
Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Inclusion Criteria:
- Liver transplant recipient
- 18 years of age or older
- ≥1 risk factor(s) for IFI: living donor transplant, retransplantation, complicated operations (based on duration of transplant and number of blood products required in the peri-transplant period), choledochojejunostomy anastomosis, or peri-operative Candida colonization, recent Candida infection, renal replacement therapy post-transplant, and reoperation within the first 90 days of transplant.
Exclusion Criteria:
- Participants who are perceived not to survive past 7 days after transplant
- Participants who elect not to participate in the prospective trial
- Participants who had active candidiasis at the time of transplant
- Participants with a history of allergy to an echinocandin
- Participants who are pregnant.
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: La prévention
- Répartition: Non randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Expérimental: Prospective Intervention Cohort
Rezafungin 400 mg IV once within 24 hours of liver transplant, followed by 200 mg IV once weekly for a total duration of 4 weeks |
Rezafungin 400 mg IV once within 24 hours of liver transplant, followed by 200 mg IV weekly for 4 weeks. |
|
Comparateur actif: Prospective Control Cohort
Patients who receive fluconazole/voriconazole or no antifungal prophylaxis as part of UPMC's risk-based antifungal prophylaxis standard of care after liver transplant |
UPMC uses a tiered approach to antifungal prophylaxis, based on risk factors for IFI. Fluconazole is used for recipients with risk factors for yeast infections: choledochojejunostomy, prolonged transplant time, receipt of >40 units of blood products within 24 hours of transplant, and Candida colonization or infection within 3 months prior to transplant. Voriconazole is used for recipients with risk factors for mould infections: re-transplantation, renal failure requiring renal replacement therapy, fulminant hepatic failure as indication for transplant, intra-abdominal/thoracic re-exploration within the first month after transplant. No prophylaxis is given if there are no risk factors for yeast or mould infections.
Autres noms:
|
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Comparateur actif: Historical Control Group
Patients at risk for IFI who received fluconazole/voriconazole for antifungal prophylaxis after liver transplant in the two years preceding the study |
UPMC uses a tiered approach to antifungal prophylaxis, based on risk factors for IFI. Fluconazole is used for recipients with risk factors for yeast infections: choledochojejunostomy, prolonged transplant time, receipt of >40 units of blood products within 24 hours of transplant, and Candida colonization or infection within 3 months prior to transplant. Voriconazole is used for recipients with risk factors for mould infections: re-transplantation, renal failure requiring renal replacement therapy, fulminant hepatic failure as indication for transplant, intra-abdominal/thoracic re-exploration within the first month after transplant. No prophylaxis is given if there are no risk factors for yeast or mould infections.
Autres noms:
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Incidence of proven and probable IFIs
Délai: 90 days post-transplant
|
Incidence of proven and probable IFIs within 90 days post-transplant |
90 days post-transplant
|
|
Incidence of proven and probable breakthrough IFI
Délai: While receiving rezafungin, voriconazole, or fluconazole
|
Incidence of breakthrough IFI while on specific antifungal prophylaxis |
While receiving rezafungin, voriconazole, or fluconazole
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Fungal-free survival
Délai: 90 days and 6 months post-transplant
|
Number of participants without fungal infection |
90 days and 6 months post-transplant
|
|
Fungal colonization
Délai: 90 days and 6 months post-transplant
|
Number of participants with presence or growth of fungi without it causing active infection or disease |
90 days and 6 months post-transplant
|
|
Graft rejection
Délai: 90 days and 6 months post-transplant
|
Number of participants with liver allograft acute rejection |
90 days and 6 months post-transplant
|
|
Graft loss
Délai: 90 days 6 months post-transplant
|
Number of participants with failure of the liver allograft to function adequately or to remain viable |
90 days 6 months post-transplant
|
|
All-cause mortality
Délai: 90 days 6 months post-transplant
|
Number of participants who die |
90 days 6 months post-transplant
|
|
Number of participants with premature discontinuation of prophylaxis
Délai: 90 days post-transplant
|
Number of patients who experience an adverse event requiring premature discontinuation of antifungal prophylaxis |
90 days post-transplant
|
|
Overall incidence of development of antifungal resistance
Délai: Within 6 months of transplant
|
Antifungal resistance of breakthrough fungal organisms or fungal organisms recovered within the first 6 months of transplant for patients who received rezafungin |
Within 6 months of transplant
|
Autres mesures de résultats
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Pharmakokinectics (PK) of rezafungin
Délai: Up to 4 weeks post-transplant
|
Pharmacokinetics of rezafungin while in ICU to assess the PK during the peri-transplant period |
Up to 4 weeks post-transplant
|
|
Stool microbiota composition
Délai: Within 6 months post-transplant
|
Stool microbiota and fecal Candida constituent and susceptibility profile in response to rezafungin |
Within 6 months post-transplant
|
Collaborateurs et enquêteurs
Parrainer
Collaborateurs
Les enquêteurs
- Chercheur principal: Fernanda Silveira, University of Pittsburgh
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- STUDY24080165
Plan pour les données individuelles des participants (IPD)
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Description du régime IPD
We do not plan to share individual participant data outside of our investigative team and collaborators. Aggregate data will be shared in publications as appropriate.
Informations sur les médicaments et les dispositifs, documents d'étude
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