This study will compare different ways of giving the drugs ganciclovir and valganciclovir to
kidney or kidney and pancreas transplant recipients to determine the most effective dose of
valganciclovir for protecting against cytomegalovirus (CMV) infection in these patients. One
of the most common viral infections following organ transplant, CMV can cause serious
illness and even death.
Ganciclovir reduces the incidence of CMV disease after kidney transplantation. The drug is
given either intravenously (through a vein) twice a day or by mouth 3 times a day.
Valganciclovir is converted to ganciclovir in the body and is absorbed into the bloodstream
better than oral ganciclovir. In most transplant patients, a single daily dose of
valganciclovir prevents CMV. Because of these advantages, some transplant patients are being
given valganciclovir instead of ganciclovir to prevent CMV infection. However, the drug has
not been studied in kidney and kidney transplant patients. This study will provide dosing
information for this patient population.
Patients 18 years of age and older who have had a kidney or kidney and pancreas transplant
at the NIH Clinical Center may be eligible for this study. Participants will undergo the
following treatments and procedures:
- Phase 1 - Treatment with intravenous ganciclovir for at least 7 days after
Sometime before starting phase 2, patients will provide a 24-hour urine collection to test
for kidney function. The day before starting phase 2, they will have a cannula (small
needle) inserted into an arm vein for about 12 hours to draw blood samples-one before
starting the ganciclovir infusion, then at 15, 30, 60, and 90 minutes, and 2, 4, 6, 8, and
12 hours after the dose.
- Phase 2 - Treatment with oral valganciclovir once a day for 7 to 21 days at a dose
approximately equivalent to intravenous ganciclovir. Sometime between 4 and 21 days on
this dose, patients will have blood sampling in the morning before taking the drug and
then at 0.5, 1, 1.5, 2, 4, 6, 8, 12, and 24 hours after the dose.
- Phase 3 - Treatment with valganciclovir at a dose reduced by half to approximate oral
After at least 4 days on this dose, patients will be admitted to the hospital for 1 day for
blood sampling before the drug dose and then at 0.5, 1, 1.5, 2, 4, 6, 8, 12, and 24 hours
after the dose. Kidney function will be assessed by blood tests within 2 days of the blood
sampling. If kidney function is not within the normal range, further dosing and blood
sampling will be delayed until kidney function returns to the normal range.
- Phase 4 - Treatment with oral ganciclovir every 8 hours. After at least 4 days on this
regimen, patients will be admitted to the hospital for 1 day for blood sampling before the
drug dose and then at 0.5, 1, 1.5, 2, 4, 6, and 8 hours after the dose. Kidney function will
be estimated by blood tests within 2 days of the blood sampling. If kidney function is not
within the normal range, further dosing and blood sampling will be delayed until kidney
function returns to normal range.
After completing phase 4, patients will continue valganciclovir daily or oral ganciclovir
treatment and blood sampling for a length of time prescribed by the transplant surgeon.
Cytomegalovirus in solid organ transplant recipients can result in significant morbidity and
mortality due to concurrent immunosuppression. Traditionally intravenous followed by oral
ganciclovir has been used to prevent and treat cytomegalovirus infection and disease in
transplant recipients. Recently a new oral form of ganciclovir, valganciclovir has been
approved by the Food and Drug Administration for the treatment of CMV retinitis in patients
with AIDS. Valganciclovir is more bioavailable and requires fewer daily doses and lower pill
burden than oral ganciclovir. In addition valganciclovir can attain ganciclovir plasma
levels similar to intravenous ganciclovir. This protocol will test the ability of
valganciclovir to provide similar drug exposure (area under the curve, AUC) as oral and
intravenous ganciclovir at equivalent doses in the setting of kidney and kidney-pancreas
transplantation. Patients will receive four different dosing/dosage form schemes.
Intravenous ganciclovir at 2.5mg/kg every 12 hours, which is the usual treatment at this
facility post surgery will be administered for approximately 7 days (phase I), then patients
will receive valganciclovir 900 mg daily for 7 to 21 days (phase II), then patients will
receive 450 mg daily for at least 4 days (phase III), and finally, ganciclovir 1000 mg every
8 hours for at least 4 days (phase IV). Serial blood samples will be collected for
pharmacokinetic analyses after each change in dose/dosage form (after each phase). After
completion of the study, patients will be maintained on valganciclovir 450 mg daily for CMV
prophylaxis or oral ganciclovir for a length of time prescribed by the transplant surgeon.
By characterizing the pharmacokinetics of valganciclovir in kidney/pancreas transplant
patients, it is hoped that appropriate dosing to prevent CMV disease and limit toxicity may
- INCLUSION CRITERIA:
Candidates receiving kidney or kidney/pancreas transplants at the Warren G. Magnuson
Clinical Center who require CMV prophylaxis.
Willingness and legal ability to give informed consent.
Estimated creatinine clearance (using MDRD 4 variable equation (16)) of greater than or
equal to 60ml/min/1.73m(2) or a 24 hour urine creatinine clearance of greater than or
equal to 60ml/min/1.73m(2).
Age less than 18 years old.
Pregnant (pregnancy test as part of transplant protocol).
Absolute neutrophil count less than 500/mm(3).
Platelet count less than 50,000/mm(3).
Severe anemia postoperatively, Hgb less than 8.0 mg/dl despite erythropoetin therapy
(subjects can be started on erythropoetin and iron supplementation post transplant).
Hypersensitivity to ganciclovir or valganciclovir.
The presence of persistent diarrhea (greater than or equal to 7 stools or stool volume
greater than 1 liter per day for greater than or equal to 3 days).