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

This study has been completed.
Sponsor:
Collaborator:
Roche Pharma AG
Information provided by (Responsible Party):
Scott Palmer, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT00227370
First received: September 26, 2005
Last updated: April 25, 2013
Last verified: April 2013
History of Changes
  Purpose

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.


Condition Intervention Phase
Cytomegalovirus Infections
 Drug: valganciclovir
Other: Placebo
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
Official Title: A Phase III, Randomized, Double-Blind Comparison of Oral Valganciclovir and Placebo for Prevention of CMV After Lung Transplantation

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Duke University:

Primary Outcome Measures:
  • Incidence of CMV End Organ Disease [ Time Frame: over the course of 300 days after randomization ] [ Designated as safety issue: No ]
    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.

  • Incidence of CMV Syndrome [ Time Frame: over the course of 300 days after randomization ] [ Designated as safety issue: No ]
    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)


Secondary Outcome Measures:
  • Any CMV Infection [ Time Frame: over the course of 300 days post randomization ] [ Designated as safety issue: No ]
    Inclusive of CMV syndrome, disease, or infection not meeting primary end point.

  • Biopsy Proven Acute Lung Rejection [ Time Frame: over the course of 300 days of randomization ] [ Designated as safety issue: No ]
  • Non-CMV Infection [ Time Frame: over the course of 300 days after randomization ] [ Designated as safety issue: No ]
    non cmv opportunistic infections

  • Severity of Viremia [ Time Frame: over the course of 300 days after randomization ] [ Designated as safety issue: No ]
    upon diagnosis of cmv disease, the number of CMV DNA copies/mL as measured by PCR

  • Ganciclovir Resistance [ Time Frame: over the course of 300 days post randomization ] [ Designated as safety issue: No ]
    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


Enrollment: 136
Study Start Date: July 2003
Study Completion Date: December 2008
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: valcyte
Placebo Comparator: 2
placebo for 9 months post lung transplant
 Other: Placebo

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00227370

Locations
United States, North Carolina
DukeUMC
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Scott Palmer
Roche Pharma AG
Investigators
Principal Investigator: Scott M Palmer, MD Duke University
  More Information

No publications provided by Duke University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Scott Palmer, Associate Professor of Medicine-Pulmonary, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT00227370     History of Changes
Other Study ID Numbers: Pro00013245, 4623 (Val038)
Study First Received: September 26, 2005
Results First Received: January 24, 2013
Last Updated: April 25, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Duke University:
Acute rejection
Non-CMV infections
Resistance

Additional relevant MeSH terms:
Cytomegalovirus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Valganciclovir
 Ganciclovir
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 16, 2013