Kidney Trasplant Clinical Trial
Official title:
Pharmacokinetics of Valganciclovir in Kidney and Kidney/Pancreas Transplant Recipients
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 transplantation.
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
ganciclovir dosing.
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 be achieved. ;