Prophylaxis Versus Preemptive Therapy for the Prevention of CMV in High-Risk R-D+ Liver Transplant Recipients
Trial status: Open for Enrollment
Why is this study being done?
Title: Prophylaxis versus Preemptive Therapy for Prevention of CMV in High-Risk R-/D+ Liver Transplant Recipients ['CAPSIL' Study]
Population: CMV seronegative recipients (18 years of age or older) of a liver transplant from a CMV seropositive donor (R-/D+)
Number of Clinical Sites: 5
Study Duration: 5 years
Subject Participation Duration: Until the closure of the study and not to exceed 5 years from enrollment.
Description of Agent or Intervention: Oral Valganciclovir hydrochloride: 2-[(2-amino-6-oxo-6,9-dihydro-3H-purin-9-yl)methoxy]-3-hydroxypropyl (2S)-2-amino-3-methylbutanoate. Currently marketed as Valcyte ®.
The primary objective is to compare prophylaxis versus preemptive therapy using valganciclovir for the prevention of CMV disease in R-/D+ liver transplant recipients
Secondary objectives :To assess the two preventive strategies for:
- Clinical outcomes (major bacterial, fungal and non-CMV viral infections, rejection, graft loss and mortality)
- Hematologic toxicity (assessment of neutropenia and receipt of hematopoietic growth factor during study days 1-107)
Study Design: This is a prospective, randomized, multicenter trial of preemptive therapy vs. prophylaxis for prevention of CMV disease in R-D+ liver transplant patients. Patients meeting study criteria and who have provided informed consent 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). Valganciclovir dosages will be adjusted for renal dysfunction. 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).
Estimated Time to Complete Enrollment: Approximately 3.5 years
Who is eligible to participate?
- Greater than 18 yrs of age
- Negative CMV serology recipient
- Positive CMV serology donor
- Liver transplant within 10 days
- Absolute neutrophil count>1000
- Female subjects of childbearing potential must have negative pregnancy test and agree to use effective contraception during and for 3 months after receipt of valganciclovir
- Male subjects, that have not had a vasectomy, must agree to practice barrier method of contraception during and for 3 months after receipt of valganciclovir
- Enrollment in other investigational drug trials
- Hypersensitivity to acyclovir, ganciclovir or valganciclovir
- Breast feeding mother
- HIV infection
- Multiple organ transplant or re-transplantation
- Life expectancy of less than 72 hours