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A Study of Valcyte (Valganciclovir) CMV Prophylaxis After Renal Transplantation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00372229
Recruitment Status : Completed
First Posted : September 6, 2006
Results First Posted : March 11, 2020
Last Update Posted : March 11, 2020
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
This 2 arm study will compare the efficacy of 100 days of Valcyte (900mg po daily) prophylaxis with that of no prophylaxis, under the condition of pre-emptive therapy of active CMV infection, in CMV positive renal transplant recipients. The influence of the two prevention concepts on the occurrence of direct and indirect effects of active CMV infections will be compared. The anticipated time on study treatment is 3 months-1 year, and the target sample size is 100-500 individuals.

Condition or disease Intervention/treatment Phase
Cytomegalovirus Infections Drug: Valganciclovir CMV Prophylaxis Drug: Valganciclovir (Pre-emptive CMV Therapy) Drug: Ganciclovir Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 299 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: A Randomized Trial Comparing Valcyte CMV Prophylaxis Versus Pre-emptive Therapy After Renal Transplantation Using Proteomics for Monitoring of Graft Alteration
Study Start Date : May 2006
Actual Primary Completion Date : October 2015
Actual Study Completion Date : October 2015


Arm Intervention/treatment
Experimental: Valganciclovir Cytomegalovirus (CMV) Prophylaxis Drug: Valganciclovir CMV Prophylaxis
900 mg valganciclovir, taken orally once daily, adjusted to renal function starting within 14 days of transplantation until Day 100 after transplantation.
Other Name: Valcyte

Active Comparator: Pre-emptive CMV Therapy Drug: Valganciclovir (Pre-emptive CMV Therapy)
If plasma polymerase chain reaction (PCR) ≥ 400 CMV copies/millilitre, then 1800 mg valganciclovir per day adjusted to renal function for at least 14 days until the second negative PCR (below 400 copies/ml) followed by secondary prophylaxis for 28 days with 900 mg valganciclovir adjusted to renal function. If CMV disease or no response to valganciclovir treatment after 14 days (not falling viral load), then intravenous (IV) ganciclovir or additional appropriate therapy could have been administered according to the local site's standard, instead of valganciclovir.
Other Name: Valcyte

Drug: Ganciclovir
If CMV disease or no response to valganciclovir treatment after 14 days (not falling viral load), then intravenous (IV) ganciclovir or additional appropriate therapy could have been administered according to the local site's standard, instead of valganciclovir.




Primary Outcome Measures :
  1. Percentage of Participants With Active Cytomegalovirus (CMV) Infection Within 12 Months [ Time Frame: Up to 12 months ]
    Active CMV infection was defined as plasma polymerase chain reaction (PCR) ≥ 400 copies/millilitre (ml).

  2. Percentage of Participants With CMV Disease Within 12 Months Including CMV Syndrome and Tissue Invasive Disease [ Time Frame: Up to 12 months ]
    CMV disease comprises the two components of CMV syndrome as well as CMV tissue invasive disease. CMV syndrome was defined as viremia according to plasma PCR ≥ 400 copies/ml and at least one of the following signs: fever of ≥38 °C; new or increased malaise (malaise defined as normal activity reduced >50%; cannot work or unable to care for self; leukopenia on 2 successive measurements separated by at least 24 hours thrombocytopenia; elevation of hepatic transaminases (alanine aminotransferase (ALT) or aspartate aminotransferase (AST) to at least 2 x upper limit of normal (ULN). CMV tissue invasive disease was defined as viremia according plasma PCR ≥ 400 copies/ml and clinical evidence of localized CMV infection (CMV inclusion cells or in situ detection of CMV antigen or deoxyribonucleic acid [DNA] by immunostaining or hybridization, respectively), cerebral spinal fluid [CSF]) and/or relevant symptoms or signs of organ dysfunction.

  3. Urine Proteomic Pattern at Month 12 [ Time Frame: Up to 12 months ]
    Proteomics is the complete set of proteins expressed by an organism, tissue, or cell. Urine proteomic pattern was measured on a scale between -1, indicating no graft alteration, and +1, indicating graft alteration.

  4. Percentage of Participants With Graft Loss at Month 84 [ Time Frame: Up to 84 months ]

Secondary Outcome Measures :
  1. Percentage of Participants With CMV Syndrome Within 12 Months [ Time Frame: Up to 12 months ]
    CMV syndrome was defined as viremia according to plasma PCR ≥ 400 copies/ml and at least one of the following signs: fever of ≥38 °C; new or increased malaise (malaise defined as normal activity reduced >50%; cannot work or unable to care for self; leukopenia on 2 successive measurements separated by at least 24 hours thrombocytopenia; elevation of hepatic transaminases (alanine aminotransferase (ALT) or aspartate aminotransferase (AST) to at least 2 x upper limit of normal (ULN).

  2. Percentage of Participants With CMV Tissue Invasive Disease Within 12 Months [ Time Frame: Up to 12 months ]
    CMV tissue invasive disease was defined as viremia: PCR ≥ 400 copies/ml and clinical evidence of localized CMV infection (CMV inclusion cells or in situ detection of CMV antigen or deoxyribonucleic acid [DNA] by immunostaining or hybridization, respectively), cerebral spinal fluid [CSF]) and/or relevant symptoms or signs of organ dysfunction.

  3. Time to Occurrence of First Viremia Within 12 Months [ Time Frame: Up to 12 months ]
    Viremia was defined as plasma PCR ≥ 400 copies/ml.

  4. Viral Burden at Viremia [ Time Frame: Up to 12 months ]
    Time-weighted area under the curve (AUC) of the polymerase chain reaction (PCR). Viremia was defined as plasma PCR ≥ 400 copies/ml.

  5. Creatinine Clearance at Month 12 [ Time Frame: Up to 12 months ]
    Creatinine clearance was estimated using the Cockcroft-Gault formula.

  6. Percentage of Participants With at Least One Treated and Biopsy-Proven Acute Rejection Episode Within 12 Months [ Time Frame: Up to 12 months ]
  7. Days of Hospitalization [ Time Frame: Up to 12 months ]
  8. Relationship Between Proteomics Pattern and Graft Survival [ Time Frame: Up to 12 months ]
    Proteomics is the complete set of proteins expressed by an organism, tissue, or cell. The proteomics of CKD273, CMV, and nephropathy was measured on a scale between -1, indicating no graft alteration, and +1, indicating graft alteration.

  9. Relationship Between Proteomics Pattern and Participant Survival [ Time Frame: Up to 12 months ]
    Proteomics is the complete set of proteins expressed by an organism, tissue, or cell. The proteomics of CKD273, CMV, and nephropathy was measured on a scale between -1, indicating no graft alteration, and +1, indicating graft alteration.

  10. Proteomics Parameter: CKD273 [ Time Frame: Up to 12 months ]
    Proteomics is the complete set of proteins expressed by an organism, tissue, or cell. The proteomics of CKD273 was measured on a scale between -1, indicating no graft alteration, and +1, indicating graft alteration.

  11. Proteomics Parameter: CMV [ Time Frame: Up to 12 months ]
    Proteomics is the complete set of proteins expressed by an organism, tissue, or cell. The proteomics of CMV was measured on a scale between -1, indicating no graft alteration, and +1, indicating graft alteration.

  12. Proteomics Parameter: Nephropathy [ Time Frame: Up to 12 months ]
    Proteomics is the complete set of proteins expressed by an organism, tissue, or cell. The proteomics of nephropathy was measured on a scale between -1, indicating no graft alteration, and +1, indicating graft alteration.

  13. Percentage of Participants Surviving at Month 12 [ Time Frame: Up to 12 months ]
  14. Percentage of Participants With Graft Survival at Month 12 [ Time Frame: Up to 12 months ]
  15. Percentage of Participants With Leukopenia Within 12 Months [ Time Frame: Up to 12 months ]
    Leukopenia: white blood cell (WBC) of < 3,500/microlitre (μL) and < 1,000/μL

  16. Percentage of Participants With Neutropenia Within 12 Months [ Time Frame: Up to 12 months ]
    Neutropenia: absolute neutrophil count (ANC) < 750/μL within 12 months.

  17. Percentage of Participants With Any Opportunistic Infection Within 12 Months [ Time Frame: Up to 12 months ]
  18. Percentage of Participants With Post-Transplant Diabetes Mellitus [ Time Frame: Up to 12 months ]
  19. Percentage of Participants With Active CMV Infections Not Responding to Valganciclovir or IV Ganciclovir Treatment [ Time Frame: Up to 12 months ]
    Active CMV infection was defined as plasma polymerase chain reaction (PCR) ≥ 400 copies/millilitre (ml).

  20. Number of Participants With CMV Viremia (Active CMV Infection) From Baseline to Month 24 and Every 12 Months up to Month 84 [ Time Frame: From Month 24 to Month 84 ]
    Viremia (active CMV Infection) was defined as PCR ≥ 400 copies/ml.

  21. Number of Participants With CMV Disease From Baseline to Month 24 and Every 12 Months up to Month 84 [ Time Frame: From Month 24 to Month 84 ]
    CMV disease comprises the two components of CMV syndrome as well as CMV tissue invasive disease. CMV syndrome was defined as viremia according to plasma PCR ≥ 400 copies/ml and at least one of the following signs: fever of ≥38 °C; new or increased malaise (malaise defined as normal activity reduced >50%; cannot work or unable to care for self; leukopenia on 2 successive measurements separated by at least 24 hours thrombocytopenia; elevation of hepatic transaminases (alanine aminotransferase (ALT) or aspartate aminotransferase (AST) to at least 2 x upper limit of normal (ULN). CMV tissue invasive disease was defined as viremia according plasma PCR ≥ 400 copies/ml and clinical evidence of localized CMV infection (CMV inclusion cells or in situ detection of CMV antigen or deoxyribonucleic acid [DNA] by immunostaining or hybridization, respectively), cerebral spinal fluid [CSF]) and/or relevant symptoms or signs of organ dysfunction.

  22. Number of Participants With CMV Syndrome From Baseline to Month 24 and Every 12 Months up to Month 84 [ Time Frame: From Month 24 to Month 84 ]
    CMV syndrome was defined as viremia according to plasma PCR ≥ 400 copies/ml and at least one of the following signs: fever of ≥38 °C; new or increased malaise (malaise defined as normal activity reduced >50%; cannot work or unable to care for self; leukopenia on 2 successive measurements separated by at least 24 hours thrombocytopenia; elevation of hepatic transaminases (alanine aminotransferase (ALT) or aspartate aminotransferase (AST) to at least 2 x upper limit of normal (ULN).

  23. Number of Participants With CMV Tissue Invasive Disease From Baseline to Month 24 and Every 12 Months up to Month 84 [ Time Frame: From Month 24 to Month 84 ]
    CMV tissue invasive disease was defined as viremia according plasma PCR ≥ 400 copies/ml and clinical evidence of localized CMV infection (CMV inclusion cells or in situ detection of CMV antigen or deoxyribonucleic acid [DNA] by immunostaining or hybridization, respectively), cerebral spinal fluid [CSF]) and/or relevant symptoms or signs of organ dysfunction.

  24. Number of Participants With Active CMV Infection After Month 24 and Every 12 Months up to Month 84 [ Time Frame: From Month 24 to Month 84 ]
    Active CMV infection was defined as plasma polymerase chain reaction (PCR) ≥ 400 copies/millilitre (ml).

  25. Number of Participants With CMV Disease After Month 24 and Every 12 Months up to Month 84 [ Time Frame: From Month 24 to Month 84 ]
    CMV disease comprises the two components of CMV syndrome as well as CMV tissue invasive disease. CMV syndrome was defined as viremia according to plasma PCR ≥ 400 copies/ml and at least one of the following signs: fever of ≥38 °C; new or increased malaise (malaise defined as normal activity reduced >50%; cannot work or unable to care for self; leukopenia on 2 successive measurements separated by at least 24 hours thrombocytopenia; elevation of hepatic transaminases (alanine aminotransferase (ALT) or aspartate aminotransferase (AST) to at least 2 x upper limit of normal (ULN). CMV tissue invasive disease was defined as viremia according plasma PCR ≥ 400 copies/ml and clinical evidence of localized CMV infection (CMV inclusion cells or in situ detection of CMV antigen or deoxyribonucleic acid [DNA] by immunostaining or hybridization, respectively), cerebral spinal fluid [CSF]) and/or relevant symptoms or signs of organ dysfunction.

  26. Percentage of Participants Surviving at Month 24 and Every 12 Months up to Month 84 [ Time Frame: From Month 24 to Month 84 ]
  27. Number of Participants Who Died From Months 24 to Month 84 [ Time Frame: From Month 24 to Month 84 ]
  28. Percentage of Participants With Graft Survival at Month 24 and Every 12 Months up to Month 84 [ Time Frame: From Month 24 to Month 84 ]
  29. Number of Participants Who Had Lost Their Transplant up to Month 84 [ Time Frame: From Month 24 to Month 84 ]
  30. Number of Participants With Active CMV Infection Who Had Lost Their Transplant up to Month 84 [ Time Frame: From Month 24 to Month 84 ]
  31. Number of Participants Without Active CMV Infection Who Had Lost Their Transplant up to Month 84 [ Time Frame: From Month 24 to Month 84 ]
  32. Kaplan-Meier Estimate of the Percentage of Participants (With Versus Without Active CMV Infection) on Valganciclovir CMV Prophylaxis With First Occurrence of Graft Loss at Month 84 [ Time Frame: Up to 84 months ]
    An analysis for the time to first occurrence of graft loss within month 84 (by means of Kaplan-Meier analysis) was done for all patients who suffered at least once from acute CMV infection (CMV viremia) during this study versus all patients who did not suffer from acute CMV infection (CMV viremia) during the study. Active CMV infection was defined as plasma polymerase chain reaction (PCR) ≥ 400 copies/millilitre (ml).

  33. Kaplan-Meier Estimate of the Percentage of Participants (With Versus Without Active CMV Infection) on Pre-emptive CMV Therapy With First Occurrence of Graft Loss at Month 84 [ Time Frame: Up to 84 months ]
    An analysis for the time to first occurrence of graft loss within month 84 (by means of Kaplan-Meier analysis) was done for all patients who suffered at least once from acute CMV infection (CMV viremia) during this study versus all patients who did not suffer from acute CMV infection (CMV viremia) during the study. Active CMV infection was defined as plasma polymerase chain reaction (PCR) ≥ 400 copies/millilitre (ml).

  34. Number of Participants Who Had Lost Their Transplant or Died up to Month 84 [ Time Frame: From Month 24 to Month 84 ]
  35. Percentage of Participants With Graft Survival or Participant Survival at Month 24 and Every 12 Months up to Month 84 [ Time Frame: From Month 24 to Month 84 ]
  36. Number of Participants With Graft Rejections by CMV Status (Positive or Negative) of the Donor at Month 24 and Every 12 Months up to Month 84 [ Time Frame: From Month 24 to Month 84 ]
  37. Number of Graft Rejections by CMV Status (Positive or Negative) of the Donor at Month 24 and Every 12 Months up to Month 84 [ Time Frame: From Month 24 to Month 84 ]
  38. Creatinine Clearance at Month 24 and Every 12 Months up to Month 84 [ Time Frame: From Month 24 to Month 84 ]
    Creatinine Clearance estimated by Cockcroft-Gault formula.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • primary or secondary renal allograft within preceding 14 days;
  • IgG seropositive for CMV;
  • receiving immunosuppressive therapy.

Exclusion Criteria:

  • active CMV infection;
  • current/history of malignancy;
  • acute steroid resistant rejection episode since transplantation.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00372229


Locations
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Austria
Innsbruck, Austria, 6020
Wien, Austria, 1090
Germany
Aachen, Germany, 52057
Berlin, Germany, 12203
Berlin, Germany, 13353
Bremen, Germany, 28205
Düsseldorf, Germany, 40225
Erlangen, Germany, 91054
Essen, Germany, 45122
Frankfurt, Germany, 60596
Freiburg, Germany, 79106
Hamburg, Germany, 20246
Hann. Münden, Germany, 34346
Hannover, Germany, 30625
Jena, Germany, 07747
Köln, Germany, 50937
Leipzig, Germany, 04103
Lübeck, Germany, 23562
Muenchen, Germany, 81377
München, Germany, 81675
Münster, Germany, 48149
Regensburg, Germany, 93053
Tübingen, Germany, 72076
Wuerzburg, Germany, 97080
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00372229    
Other Study ID Numbers: ML19313
First Posted: September 6, 2006    Key Record Dates
Results First Posted: March 11, 2020
Last Update Posted: March 11, 2020
Last Verified: February 2020
Additional relevant MeSH terms:
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Valganciclovir
Cytomegalovirus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Ganciclovir
Ganciclovir triphosphate
Antiviral Agents
Anti-Infective Agents
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action