Comparison of Oral Valganciclovir and Placebo for the Prevention of Cytomegalovirus (CMV) After Lung Transplantation

A Phase III, Randomized, Double-Blind Comparison of Oral Valganciclovir and Placebo for Prevention of CMV After Lung Transplantation

The study evaluated the efficacy and safety of a prolonged, continuous course of Valganciclovir (Valgan) in the prevention of CMV by comparing 3 months of Vaglanciclovir, the standard of care upon initiation of the study, to 12 months of Valganciclovir.

A multi-center two phase, double-blind, placebo controlled, randomized prospective study of 130 lung transplant recipients. Patients will be screened and consented prior to transplant. All consented patients will receive IV ganciclovir within 24 hours of transplant for not more than 14 days. Patients will enroll in Phase I of the study is an open label safety and efficacy analysis of three months of oral valganciclovir in adult transplant recipients who are at risk for CMV. After completion of 3 months of open label therapy, patients that meet the criteria for Phase II of the study will be randomized to 9 months of blinded therapy (Placebo/Valgan). Phase II of the study is designed to assess the efficacy of short course sequential IV ganciclovir followed by oral valganciclovir as compared to the extended period of oral valganciclovir prophylaxis in the prevention of CMV disease in at risk lung transplant recipients

Inclusion Criteria for Phase I:

• Adult lung transplant recipients age 18 or older
• At risk for CMV (donor or recipient serology must be positive for CMV)
• Adequate hematological and renal function,
• On intravenous (IV) ganciclovir within 24 hours of surgery
• Agreement to use effective methods of contraception
• Negative pregnancy
• Tolerate oral medications within 2 weeks of transplant
• Negative baseline CMV PCR
• Able to understand and sign the informed consent

Exclusion Criteria for Phase 1:

• Repeat transplantation
• Mechanical ventilation at study entry
• Oral or intravenous ganciclovir treatment outside the study protocol
• Invasive fungal infection
• Participation in another investigational study
• Acute CMV infection or disease
• Anti-CMV therapy within 30 days before enrollment
• Uncontrolled diarrhea or malabsorption
• Allergic reaction to study drug
• Required use of prohibited medications
• Lactating women
• Pregnancy
• Renal failure

Inclusion Criteria for Phase II:

• Negative serial post transplant PCRs at day 75
• Negative bronchial cultures for CMV
• Adequate hematological and renal function at day 75
• IV ganciclovir for up to 2 weeks post operation and open label up to day 90
• Effective contraceptives
• Negative pregnancy

Exclusion Criteria Phase II:

• Renal failure
• Serious adverse events (SAE) related to study drug
• CMV disease (study endpoint)
• Withdraw consent for Phase II