Maribavir Versus Oral Ganciclovir For The Prevention of Cytomegalovirus (CMV) Disease in Liver Transplant Recipients
- Registration Number
- NCT00497796
- Lead Sponsor
- Shire
- Brief Summary
The purpose of this research study is to investigate whether or not oral maribavir is safe and effective compared to oral ganciclovir for preventing CMV disease when administered for up to 14 weeks in patients who have had a liver transplant.
- Detailed Description
Cytomegalovirus (CMV) infections remain a significant problem following various types of transplants that are associated with strong immunosuppressive therapy. Maribavir is a new oral anti-CMV drug with a novel mechanism of action compared to currently available anti-CMV drugs. This study will test the safety and efficacy of maribavir for the prevention of CMV disease when given as prophylaxis for up to 14 weeks following orthotopic liver transplantation.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 307
- Orthotopic liver transplant recipient
- Donor CMV seropositive / Recipient CMV seronegative
- Enrolled within 10 days after liver transplant
- Able to swallow tablets
- Multiple organ transplant
- HIV infection
- CMV disease
- Use of other anti-CMV therapy at time of enrollment
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 1 maribavir - 2 ganciclovir -
- Primary Outcome Measures
Name Time Method Number of Participants With Endpoint Committee (EC)-Confirmed Cytomegalovirus (CMV) Disease Within 6 Months Post-Transplantation 6 months post-transplant All investigator-determined (protocol-defined) cases of CMV disease (i.e., symptomatic CMV infection or CMV organ disease), were adjudicated by an independent, blinded EC. Symptomatic CMV infection was defined as: CMV infection detected by a positive result from a CMV laboratory assay from at least one central laboratory assay (pp65 antigenemia or CMV DNA polymerase chain reaction \[PCR\] assay in plasma) and fever \>/=38 °C on \>/=2 occasions \>/=24 hours apart within a 7-day period and at least one of the following: new or increased malaise, two successive measurements of leucopenia (white blood cell \[WBC\] count \<3500/mm3 or a WBC count decrease of 20% if the cell count prior to onset of clinical symptoms was \>4000/mm3) \>/=24 hours apart, atypical lymphocytosis \>/=5%, and thrombocytopenia. CMV organ disease was defined as described by Ljungman et al., 2002.
- Secondary Outcome Measures
Name Time Method Number of Participants With Investigator-determined CMV Disease Through 6 months post-transplant (Day 1 to 100 days and 6 months post-transplant) Symptomatic CMV infection was defined as: CMV infection detected by a positive result from a CMV laboratory assay from at least one central laboratory assay (pp65 antigenemia or CMV DNA polymerase chain reaction \[PCR\] assay in plasma) and fever \>/=38 °C on \>/=2 occasions \>/=24 hours apart within a 7-day period and at least one of the following: new or increased malaise, two successive measurements of leucopenia (white blood cell \[WBC\] count \<3500/mm3 or a WBC count decrease of 20% if the cell count prior to onset of clinical symptoms was \>4000/mm3) \>/=24 hours apart, atypical lymphocytosis \>/=5%, and thrombocytopenia. CMV organ disease was defined as described by Ljungman et al., 2002.
Number of Participants Who Died Within 6 Months Post-Transplantation 6 months post-transplant Percent of Participants With Signs of Bone Marrow Suppression 15 weeks Bone marrow suppression was assessed by the occurrence of adverse events (AEs) of investigator-reported leukopenia, neutropenia, thrombocytopenia, and pancytopenia; absolute neutrophil count (ANC) \<1000/mm3; white blood cell (WBC) count toxicity grade shifts from 0-2 at baseline to a maximum of 3-4 post-baseline; and use of hematopoietic growth factors during the 6 month post-transplant period.
Plasma Concentration of Maribavir During Treatment 12 hours post-dose after 2, 6, and 10 weeks of treatment For the first 16 subjects to have PK profiling performed, PK sampling was collected at Weeks 2, 6 and 10. For subsequent subjects that have PK profiling performed, PK sampling was collected at Weeks 2 and 6. Samples were collected 12 hours after the morning dose of maribavir. Permissible assessment windows for pharmacokinetic profile sampling purposes were +/- 5 days for each sampling day. Samples for determination of maribavir concentration were analyzed by a validated liquid chromatography tandem mass spectrometry (LC/MS/MS) method. For plasma, the minimum detectable concentration for maribavir was 0.2 μg/mL.
Number of Participants With CMV Infection or EC-confirmed CMV Disease Within 6 Months Post-Transplantation 6 months post-transplant Incidence of CMV infection or EC-confirmed CMV disease within the 6-month post-transplant period included in this section were defined (1) with infection assessed by pp65 antigenemia assay; (2) with infection assessed by CMV DNA PCR; (3) with infection assessed by either assay (pp65 antigenemia or CMV DNA PCR); and (4) with infection assessed by initiation of anti-CMV therapy.
Time to Onset of CMV Infection or EC-confirmed CMV Disease Within 6 Months Post-Transplantation 6 months post-transplant All investigator-determined (protocol-defined) cases of CMV disease (i.e., symptomatic CMV infection or CMV organ disease) were adjudicated by an independent, blinded EC. CMV infection was assessed by pp65 Antigenemia or CMV DNA PCR from a central or local lab. CMV organ disease was defined as described by Ljungman et al., 2002.
Number of Participants With Retransplantation Through 6 months post-transplant (From Day 1 to 100 days and 6 months post-transplant) Number of Participants With EC-confirmed CMV Disease Within 100 Days Post-Transplantation 100 days post-transplant All investigator-determined (protocol-defined) cases of CMV disease (i.e., symptomatic CMV infection or CMV organ disease), were adjudicated by an independent, blinded EC. Symptomatic CMV infection was defined as: CMV infection detected by a positive result from a CMV laboratory assay from at least one central laboratory assay (pp65 antigenemia or CMV DNA polymerase chain reaction \[PCR\] assay in plasma) and fever \>/=38 °C on \>/=2 occasions \>/=24 hours apart within a 7-day period and at least one of the following: new or increased malaise, two successive measurements of leucopenia (white blood cell \[WBC\] count \<3500/mm3 or a WBC count decrease of 20% if the cell count prior to onset of clinical symptoms was \>4000/mm3) \>/=24 hours apart, atypical lymphocytosis \>/=5%, and thrombocytopenia. CMV organ disease was defined as described by Ljungman et al., 2002.
Number of Participants With Graft Failure Related Death Through 6 months post-transplant (From Day 1 to 100 days and 6 months post-transplant) Number of Participants With Acute Graft Rejection 26 weeks post-transplant Rejection was assessed by examining a liver biopsy sample. Diagnosis of graft rejection included a global assessment grade and a rejection activity index score.
Number of Participants With CMV Infection or EC-confirmed CMV Disease Within 100 Days Post-Transplantation 100 days post-transplant Incidence of CMV infection or EC-confirmed CMV disease within the 6-month post-transplant period included in this section were defined (1) with infection assessed by pp65 antigenemia assay; (2) with infection assessed by CMV DNA PCR; (3) with infection assessed by either assay (pp65 antigenemia or CMV DNA PCR); and (4) with infection assessed by initiation of anti-CMV therapy.
Plasma Concentration of Maribavir Metabolite VP 44469 During Treatment 12 hours post-dose after 2, 6, and 10 weeks of treatment For the first 16 subjects to have PK profiling performed, PK sampling was collected at Weeks 2, 6 and 10. For subsequent subjects that have PK profiling performed, PK sampling was collected at Weeks 2 and 6. Samples were collected 12 hours after the morning dose of maribavir. Permissible assessment windows for pharmacokinetic profile sampling purposes were +/- 5 days for each sampling day. Samples for determination of VP 44469 (a metabolite of maribavir) concentration were analyzed by a validated liquid chromatography tandem mass spectrometry (LC/MS/MS) method. For plasma, the minimum detectable concentration for VP 44469 was 0.2 μg/mL.
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Trial Locations
- Locations (55)
Mayo Clinic Arizona
🇺🇸Phoenix, Arizona, United States
University of California at San Diego
🇺🇸La Jolla, California, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
UCLA Medical Center
🇺🇸Los Angeles, California, United States
University of California at San Francisco
🇺🇸San Francisco, California, United States
Stanford University Medical Center
🇺🇸Stanford, California, United States
University of Colorado Health Sciences Center
🇺🇸Aurora, Colorado, United States
Georgetown University
🇺🇸Washington, District of Columbia, United States
Mayo Clinic College of Medicine
🇺🇸Jacksonville, Florida, United States
Tampa General
🇺🇸Tampa, Florida, United States
Scroll for more (45 remaining)Mayo Clinic Arizona🇺🇸Phoenix, Arizona, United States