Clinical trial NCT00227370: Comparison of Oral Valganciclovir and Placebo for the Prevention of Cytomegalovirus (CMV) After Lung Transplantation
Official title: A Phase III, Randomized, Double-Blind Comparison of Oral Valganciclovir and Placebo for Prevention of CMV After Lung Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cytomegalovirus Infections
Keywords: Acute rejection
Non-CMV infections
Resistance
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Roche Pharma AG
First posted: 2005-09-28
Enrollment: 136
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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

Eligibility 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

Primary outcomes:
measure: Incidence of CMV End Organ Disease
timeFrame: over the course of 300 days after randomization
measure: Incidence of CMV Syndrome
timeFrame: over the course of 300 days after randomization
Secondary outcomes:
measure: Any CMV Infection
timeFrame: over the course of 300 days post randomization
measure: Biopsy Proven Acute Lung Rejection
timeFrame: over the course of 300 days of randomization
measure: Non-CMV Infection
timeFrame: over the course of 300 days after randomization
measure: Severity of Viremia
timeFrame: over the course of 300 days after randomization
measure: Ganciclovir Resistance
timeFrame: over the course of 300 days post randomization
Other outcomes:
Locations:
city: Durham
country: United States
facility: DukeUMC
state: North Carolina
Study officials:
affiliation: Duke University
name: Scott M Palmer, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Palmer SM, Limaye AP, Banks M, Gallup D, Chapman J, Lawrence EC, Dunitz J, Milstone A, Reynolds J, Yung GL, Chan KM, Aris R, Garrity E, Valentine V, McCall J, Chow SC, Davis RD, Avery R. Extended valganciclovir prophylaxis to prevent cytomegalovirus after lung transplantation: a randomized, controlled trial. Ann Intern Med. 2010 Jun 15;152(12):761-9. doi: 10.7326/0003-4819-152-12-201006150-00003.