CMV Viremia, EBV Viremia
Conditions
Keywords
EBV Viremia in posttransplant kidney recipients, CMV viremia in posttransplant kidney recipients
Brief summary
The aim of our study is to reduce viral (CMV and EBV) transmission from donor to recipient. The discovery that anti-retroviral therapy to mothers with HIV reduced transmission of the virus to their babies was pivotal to the prevention of AIDS and so along the same lines the investigators will test the hypothesis that 14 days of the anti-viral Valganciclovir (VAL) to kidney donors prior to the transplant compared to placebo will reduce EBV and CMV viremia in the 1st year posttransplant in pediatric kidney recipients.
Detailed description
The potency of new immunosuppressive agents has reduced the risk of the body's immune system rejecting a transplanted kidney. However, this has come with a price. Kidney transplant recipients now face a higher risk of serious infections and related malignancies. Viral infections are a significant cause of posttransplant morbidity and mortality and two of the herpes viruses have the greatest impact: Epstein-Barr virus (EBV) and Cytomegalovirus (CMV). CMV disease can manifest posttransplant as fever, leukopenia, or mild to severe organ involvement (including pneumonitis, hepatitis, pancreatitis, colitis, meningoencephalitis, and rarely myocarditis). EBV can present posttransplant as infectious mononucleosis syndrome, hepatitis and, in the worse case scenario, a potentially fatal lymphoproliferative disorder called Post-Transplant Lymphoproliferative Disease (PTLD). Moreover, subclinical CMV and/or EBV viremia have been associated with deterioration in kidney function in kidney transplant recipients. Thus, the potential negative impact of these viruses on the lives of transplant recipients is profound and, unfortunately, the complications of these post-transplant viral infections are common and occur despite standard antiviral prophylaxis in the first year posttransplant. These viral infections, in most instances, originate from the donor organ where these viruses reside in a dormant state, counterbalanced by the donor's healthy immune system. Upon transplantation into the recipient, whose immune system is then severely suppressed by anti-rejection drugs, these viruses become activated, often leading to the above described complications. The aim of our study is to reduce viral (CMV and EBV) transmission from donor to recipient. The discovery that anti-retroviral therapy to mothers with HIV reduced transmission of the virus to their babies was pivotal to the prevention of AIDS and so along the same lines the investigators will test the hypothesis that 14 days of the anti-viral Valganciclovir (VAL) to kidney donors prior to the transplant compared to placebo will reduce EBV and CMV viremia in the 1st year posttransplant in pediatric kidney recipients. We aim to enroll 20 donor-recipient pairs.
Interventions
DRUGValganciclovir
Valganciclovir 450mg twice a day for 14 days prior to transplant date
DRUGPlacebo
1 capsule twice a day for 14 days prior to transplant date
Sponsors
University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Months to No maximum
Healthy volunteers
No
Inclusion criteria
* Any person approved as a kidney transplant donor with a recipient who has never undergone a previous transplantation * Kidney transplant donor must be 18 years old or older * The kidney transplant donor must be positive for CMV IgG and / or EBV IgG * The donor must be to a recipient that is discordantly seronegative for the virus for which the donor is seropositive (D+ R-) * They must have provided signed informed consent * The potential donors must be willing to contribute samples of blood and oral washings at regular intervals * The potential donor must state willingness to use effective contraception during treatment and 30 days following receiving the study drug/placebo * All females must have a negative pregnancy test * Person must have estimated creatinine clearance (Cockcroft and Gault method) \>= 60 ml/min * Person must have Absolute neutrophil count \>= 1000 cells/uL * Person must have Platelets \>= 100,000/uL * Person must have Hemoglobin \>= 9.5 g/dL
Exclusion criteria
* Any potential kidney transplant donor who is seronegative for both CMV & EBV IgG * Any potential kidney transplant donor who is receiving or have received anti-herpes medication in the past week * Any potential kidney transplant donor to a recipient who has received a previous solid organ transplant * Any potential kidney transplant donor who is immunosuppressed due to medical disease and/or immunosuppressive or immunomodulating medications * Any potential kidney transplant donor who is breast feeding during the study * Any potential kidney transplant donor who is on corticosteroids
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of EBV or CMV Related Disease in Transplant Recipient | At least 1 year | Incidence of EBV or CMV related disease in the transplant recipients of enrolled donors. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Eligible consenting kidney transplant donors who are randomized to receive placebo will be given 1 placebo in morning and 1 in evening for 14 days prior to transplant date
Placebo: 1 capsule twice a day for 14 days prior to transplant date | 10 |
| Valganciclovir Eligible consenting kidney transplant donors who are randomized to the experimental arm of the study will receive 450mg of Valganciclovir twice a day for 14 days prior to the transplant date
Valganciclovir: Valganciclovir 450mg twice a day for 14 days prior to transplant date | 7 |
| Total | 17 |
Baseline characteristics
| Characteristic | Placebo | Valganciclovir | Total |
|---|---|---|---|
| Age, Continuous | 43.4 years | 47 years | 44.8 years |
| Region of Enrollment United States | 10 participants | 7 participants | 17 participants |
| Sex: Female, Male Female | 7 Participants | 6 Participants | 13 Participants |
| Sex: Female, Male Male | 3 Participants | 1 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 10 | 0 / 7 |
| serious Total, serious adverse events | 0 / 10 | 0 / 7 |
Outcome results
Primary
Incidence of EBV or CMV Related Disease in Transplant Recipient
Incidence of EBV or CMV related disease in the transplant recipients of enrolled donors.
Time frame: At least 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Incidence of EBV or CMV Related Disease in Transplant Recipient | 2 participants |
| Valganciclovir | Incidence of EBV or CMV Related Disease in Transplant Recipient | 0 participants |