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

Cytomegalovirus Infections Clinical Trial

— Valgan  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00227370
• Other study ID #: Pro00013245
• Secondary ID: 4623 (Val038)
• Status: Completed
• Phase: Phase 3
• First received: September 26, 2005
• Last updated: April 25, 2013
• Start date: July 2003
• Est. completion date: December 2008

Study information

• Verified date: April 2013
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 136
• Est. completion date: December 2008
• Est. primary completion date: April 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Cytomegalovirus Infections

Intervention

Drug:
• valganciclovir
valgan 900mg QD x 9 months post lung transplant

Other:
• Placebo

Locations

Country	Name	City	State
United States	DukeUMC	Durham	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Scott Palmer	Roche Pharma AG

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of CMV End Organ Disease	The primary study end point was CMV end-organ disease determined by positive tissue immunostain or characteristic histopathology assessed for within 300 days post randomization.	over the course of 300 days after randomization	No
Primary	Incidence of CMV Syndrome	CMV clinical syndrome, with either positive serum PCR or positive culture for CMV from bronchoalveolar lavage and at least 2 of the following: fever, leukopenia, thrombocytopenia, elevated liver function test results malaise, reduction in pulmonary function (FEV1) greater than 20percent of baseline, or radiographic infiltrate consistent with CMV (all in the absence of other causes)	over the course of 300 days after randomization	No
Secondary	Any CMV Infection	Inclusive of CMV syndrome, disease, or infection not meeting primary end point.	over the course of 300 days post randomization	No
Secondary	Biopsy Proven Acute Lung Rejection		over the course of 300 days of randomization	No
Secondary	Non-CMV Infection	non cmv opportunistic infections	over the course of 300 days after randomization	No
Secondary	Severity of Viremia	upon diagnosis of cmv disease, the number of CMV DNA copies/mL as measured by PCR	over the course of 300 days after randomization	No
Secondary	Ganciclovir Resistance	UL97 genotyping was done on all positive samples for CMV DNA at 1000 copies/mL, with resistance defined by the presence of 1 or more mutations shown by marker transfer to confer phenotypic ganciclovir resistance	over the course of 300 days post randomization	No