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

Condition(s) targeted: Cytomegalovirus Infections

Intervention: valganciclovir (Drug); valganciclovir (Drug)

Phase: Phase 3

Status: Active, not recruiting

Sponsored by: Duke University

Official(s) and/or principal investigator(s):
Scott M Palmer, MD, Principal Investigator, Affiliation: Duke University

The purpose of this study is to determine the rate of CMV at one year in the short course (Phase I of the study) as compared to extended prophylaxis in Phase II of the study.

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

Study design: Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome:

For Enrollment Phase , using descriptive statistics, the safety and efficacy of an open label regimen that includes initial intravenous ganciclovir followed by oral valganciclovir for 3 months post transplant for patients at risk for CMV

For Randomization Phase , determine the rate of CMV disease at one year in the short course as compared to extended prophylaxis groups in Phase II

Secondary outcome:

Determine whether prevention of CMV disease after transplantation improves clinical outcomes. The researchers will compare the rates of acute rejection, hospitalization, non-CMV infections, and survival between the 2 groups over the study period.

Determine how treatment with valganciclovir affects quality of life (QOL) by comparing serial measures of QOL between groups

Determine how one year of oral valganciclovir affects ganciclovir resistance by comparing the rate of resistance between the groups

Detailed description: 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

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

DukeUMC, Durham, North Carolina 27710, United States

Starting date: July 2003
Ending date: January 2008
Last updated: January 2, 2008