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

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.

Study Overview

• Status: Completed
• Conditions: Cytomegalovirus Infections
• Intervention / Treatment: Other: Placebo; Drug: 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

• Study Type: Interventional
• Enrollment (Actual): 136
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • DukeUMC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; Valganciclovir 900 mg QD for 9 months post lung transplant.	Drug: valganciclovir; valgan 900mg QD x 9 months post lung transplant; Other Names: valcyte
Placebo Comparator: 2; placebo for 9 months post lung transplant	Other: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Any CMV Infection	Inclusive of CMV syndrome, disease, or infection not meeting primary end point.	over the course of 300 days post randomization
Biopsy Proven Acute Lung Rejection		over the course of 300 days of randomization
Non-CMV Infection	non cmv opportunistic infections	over the course of 300 days after randomization
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
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

Collaborators and Investigators

• Sponsor: Scott Palmer
• Collaborators: Roche Pharma AG
• Investigators: Principal Investigator: Scott M Palmer, MD, Duke University

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: July 1, 2003
• Primary Completion (Actual): April 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: September 26, 2005
• First Submitted That Met QC Criteria: September 26, 2005
• First Posted (Estimate): September 28, 2005

Study Record Updates

• Last Update Posted (Estimate): April 29, 2013
• Last Update Submitted That Met QC Criteria: April 25, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Keywords: Resistance; Acute rejection; Non-CMV infections
• Additional Relevant MeSH Terms: Virus Diseases; Infections; DNA Virus Infections; Herpesviridae Infections; Cytomegalovirus Infections; Anti-Infective Agents; Antiviral Agents; Valganciclovir
• Other Study ID Numbers: Pro00013245; 4623 (Val038) (Other Identifier: Alternative study ID)