CMV Antiviral Prevention Strategies in D+R-Liver Transplants ("CAPSIL")
29 juillet 2021 mis à jour par: National Institute of Allergy and Infectious Diseases (NIAID)
Prophylaxis Versus Preemptive Therapy for the Prevention of CMV in High-Risk R-D+ Liver Transplant Recipients
This is a trial of preemptive therapy vs. prophylaxis for prevention of Cytomegalovirus (CMV) disease in R-D+ liver transplant patients.
Subjects will be randomized within 10 days of transplant to receive in an open label design, either antiviral prophylaxis with valganciclovir, 900 mg orally once daily or preemptive therapy (weekly monitoring for CMV viremia by plasma PCR) for 100 days post-randomization with initiation of oral valganciclovir 900mg orally twice daily at onset of CMV viremia and continued until plasma PCR is negative on two consecutive weekly PCR tests).
A minimum of 176 subjects will be enrolled in the study.
The study duration is 7 years.
The primary objective of this study is to compare prophylaxis versus preemptive therapy using valganciclovir for the prevention of CMV disease in R-/D+ liver transplant recipients.
Aperçu de l'étude
Statut
Complété
Les conditions
Intervention / Traitement
Description détaillée
This is a prospective, randomized, multicenter trial of preemptive therapy vs. prophylaxis for prevention of Cytomegalovirus (CMV) disease in seronegative recipient- seropositive donor (R-D+) liver transplant patients.Subjects will be randomized within 10 days of transplant to receive in an open label design, either antiviral prophylaxis with valganciclovir 900 mg orally once daily or preemptive therapy for 100 days post-randomization with initiation of oral valganciclovir 900mg orally twice daily at onset of CMV viremia (monitored weekly) and continued until plasma PCR is negative on two consecutive weekly PCR tests.
Study participants will be followed during the intervention period (100 days post randomization) and until 12 months post-transplant for CMV disease, toxicity, and clinical outcomes (opportunistic infections, rejection, graft loss and mortality).
Drug safety labs will be assessed and recorded for the entire treatment period in both the prophylaxis and preemptive group.
Re-transplantation and all-cause mortality will also be assessed at study closure and no longer than 5 years after enrollment.
Additionally, the impact of the two CMV prevention strategies on CMV-specific cellular and humoral immune responses will be evaluated at 100 days after randomization, and 6 and 12 months post-transplant.
A minimum of 176 subjects will be enrolled in the study.
Allowing for over-enrollment to replace dropouts, up to 205 subjects may be enrolled to achieve the target enrollment of 176.
Subjects will be randomized into one of the two groups in 1:1 ratio.
The study duration is 7 years.
The primary objective of this study is to compare prophylaxis versus preemptive therapy using valganciclovir for the prevention of CMV disease in R-/D+ liver transplant recipients.
The secondary objectives are:1) to assess the two preventive strategies for clinical outcomes (major bacterial, fungal and non-CMV viral infections, rejection, graft loss and mortality) at one year post transplantation; 2) to assess the two preventive strategies for hematologic toxicity (assessment of neutropenia and receipt of hematopoietic growth factor during study days 1-107).
Type d'étude
Interventionnel
Inscription (Réel)
205
Phase
- Phase 4
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.
Lieux d'étude
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California
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Los Angeles, California, États-Unis, 90095-8358
- Ronald Reagan University of California Los Angeles Medical Center
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Georgia
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Atlanta, Georgia, États-Unis, 30322-1013
- Emory Clinic - Transplant Center
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Minnesota
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Rochester, Minnesota, États-Unis, 55905-0001
- Mayo Clinic, Rochester - Infectious Diseases
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New York
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New York, New York, États-Unis, 10029-6504
- Mount Sinai School of Medicine - Medicine - Infectious Diseases
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Pennsylvania
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Pittsburgh, Pennsylvania, États-Unis, 15213-3403
- University of Pittsburgh - Medicine - Infectious Diseases
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Washington
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Seattle, Washington, États-Unis, 98195-7110
- University of Washington - Medicine
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-
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
18 ans à 99 ans (Adulte, Adulte plus âgé)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
La description
Inclusion Criteria:
- Be > / = 18 years of age.
- Have negative Cytomegalovirus (CMV) serology (confirmed within 6 months of transplant) and receive a liver from a donor with positive CMV serology (R-/D+).
- Have received their first orthotopic liver transplant (the transplanted liver may be deceased donor or live donor graft) within 10 days prior.
- Have absolute neutrophil count > 1000/µL at randomization.
- If female, and not postmenopausal or surgically sterile, must have negative pregnancy test (serum or urine) within 48 hours prior to randomization and must also agree to use medically approved method of contraception. Acceptable methods include: barrier method, intrauterine device (hormonal or non-hormonal), oral hormonal contraceptives, abstinence for 100 days after randomization and 3 months after valganciclovir cessation.
-- If male, and has not had a vasectomy, he must agree to practice barrier method of contraception for 100 days after randomization and 3 months after valganciclovir cessation.
- Subject or legally authorized representative has provided written informed consent.
Exclusion Criteria:
- Currently enrolled in any interventional trial of an investigational therapeutic agent unless co-enrollment has been approved by study Principal Investigators (PIs) and the DMID prior to enrollment.
- Have hypersensitivity to acyclovir, ganciclovir or valganciclovir.
- Be breast-feeding mother.
- Have known Human immunodeficiency virus (HIV) infection (based on testing performed during the transplant evaluation process).
- Be undergoing multi organ transplant or have undergone prior organ transplant.
- Have expected life expectancy of less than 72 hours.
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 parallèle
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Expérimental: Preemptive Therapy
900 mg of Valganciclovir given orally twice daily to Preemptive Therapy subjects upon detection of CMV viremia until plasma PCR is negative on two consecutive weekly PCR test.
All dosages adjusted for renal dysfunction.
n=88
|
Valganciclovir, 900 mg given orally once daily to all Prophylaxis group subjects for 100 days post transplantation as prophylaxis.
Valganciclovir, 900 mg given orally twice daily to Preemptive Therapy group subjects as a PET only after a positive CMV PCR test and stopped after PCR is negative for 2 consecutive weeks.
|
|
Comparateur actif: Prophylaxis
900 mg of Valganciclovir given orally once daily to subjects for 100 days post transplantation.
All dosages adjusted for renal dysfunction.
n=88
|
Valganciclovir, 900 mg given orally once daily to all Prophylaxis group subjects for 100 days post transplantation as prophylaxis.
Valganciclovir, 900 mg given orally twice daily to Preemptive Therapy group subjects as a PET only after a positive CMV PCR test and stopped after PCR is negative for 2 consecutive weeks.
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Incidence of Cytomegalovirus (CMV) Disease.
Délai: 365 days post-transplant
|
CMV disease as verified by an independent end point committee
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365 days post-transplant
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
All-cause Mortality
Délai: Up to 365 days post-transplant
|
Survival probability at 1 year
|
Up to 365 days post-transplant
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Incidence of Allograft Rejection
Délai: Up to 365 days post-transplant
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Number of subjects with allograft rejection
|
Up to 365 days post-transplant
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Graft Loss
Délai: Up to 365 days post-transplant
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Incidence of graft loss (re-transplantation)
|
Up to 365 days post-transplant
|
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Late-onset CMV Disease
Délai: Up to 365 days post-transplant
|
Incidence of late-onset CMV disease (occurring after 100 days post-randomization) as adjudicated by end point committee
|
Up to 365 days post-transplant
|
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Bacterial Infections
Délai: Up to 365 days post-transplant
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Incidence of bacterial opportunistic infections
|
Up to 365 days post-transplant
|
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Major Fungal Infections
Délai: Up to 365 days post-transplant
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Opportunistic fungal infections
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Up to 365 days post-transplant
|
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Major Non-CMV Viral Infections
Délai: Up to 365 days post-transplant
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Incidence of non-CMV viral infections
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Up to 365 days post-transplant
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Neutropenia
Délai: Day 1 through Day 107
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Incidence of neutropenia less than 1000/µL while on valganciclovir treatment
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Day 1 through Day 107
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Neutropenia Less Than 500
Délai: prior to day 107
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ANC less than 500 while on valganciclovir
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prior to day 107
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Hematopoietic Growth Factors
Délai: Day 1 through Day 107
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Hematopoietic growth factor receipt for ANC less than 500 during valganciclovir treatment.
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Day 1 through Day 107
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Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Publications et liens utiles
La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.
Publications générales
- Singh N, Winston DJ, Razonable RR, Lyon GM, Silveira FP, Wagener MM, Limaye AP. Risk Factors for Cytomegalovirus Viremia following Liver Transplantation With a Seropositive Donor and Seronegative Recipient Receiving Antiviral Therapy. J Infect Dis. 2021 Mar 29;223(6):1073-1077. doi: 10.1093/infdis/jiaa470.
- Singh N, Winston DJ, Razonable RR, Lyon GM, Silveira FP, Wagener MM, Stevens-Ayers T, Edmison B, Boeckh M, Limaye AP. Effect of Preemptive Therapy vs Antiviral Prophylaxis on Cytomegalovirus Disease in Seronegative Liver Transplant Recipients With Seropositive Donors: A Randomized Clinical Trial. JAMA. 2020 Apr 14;323(14):1378-1387. doi: 10.1001/jama.2020.3138.
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 (Réel)
29 octobre 2012
Achèvement primaire (Réel)
22 juin 2018
Achèvement de l'étude (Réel)
22 juin 2018
Dates d'inscription aux études
Première soumission
2 mars 2012
Première soumission répondant aux critères de contrôle qualité
8 mars 2012
Première publication (Estimation)
13 mars 2012
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
26 août 2021
Dernière mise à jour soumise répondant aux critères de contrôle qualité
29 juillet 2021
Dernière vérification
22 mars 2018
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- 11-0073
Informations sur les médicaments et les dispositifs, documents d'étude
Étudie un produit pharmaceutique réglementé par la FDA américaine
Oui
Étudie un produit d'appareil réglementé par la FDA américaine
Non
produit fabriqué et exporté des États-Unis.
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 .