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

February 26, 2020 updated by: Hoffmann-La Roche

A Randomized Trial Comparing Valcyte CMV Prophylaxis Versus Pre-emptive Therapy After Renal Transplantation Using Proteomics for Monitoring of Graft Alteration

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
299

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Innsbruck, Austria, 6020
      • Wien, Austria, 1090
  • Germany
      • Aachen, Germany, 52057
      • Berlin, Germany, 13353
      • Berlin, Germany, 12203
      • 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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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 Names:
  • 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 Names:
  • 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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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).
Up to 12 months
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.
Up to 12 months
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.
Up to 12 months
Percentage of Participants With Graft Loss at Month 84
Time Frame: Up to 84 months
Up to 84 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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).
Up to 12 months
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.
Up to 12 months
Time to Occurrence of First Viremia Within 12 Months
Time Frame: Up to 12 months
Viremia was defined as plasma PCR ≥ 400 copies/ml.
Up to 12 months
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.
Up to 12 months
Creatinine Clearance at Month 12
Time Frame: Up to 12 months
Creatinine clearance was estimated using the Cockcroft-Gault formula.
Up to 12 months
Percentage of Participants With at Least One Treated and Biopsy-Proven Acute Rejection Episode Within 12 Months
Time Frame: Up to 12 months
Up to 12 months
Days of Hospitalization
Time Frame: Up to 12 months
Up to 12 months
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.
Up to 12 months
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.
Up to 12 months
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.
Up to 12 months
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.
Up to 12 months
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.
Up to 12 months
Percentage of Participants Surviving at Month 12
Time Frame: Up to 12 months
Up to 12 months
Percentage of Participants With Graft Survival at Month 12
Time Frame: Up to 12 months
Up to 12 months
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
Up to 12 months
Percentage of Participants With Neutropenia Within 12 Months
Time Frame: Up to 12 months
Neutropenia: absolute neutrophil count (ANC) < 750/μL within 12 months.
Up to 12 months
Percentage of Participants With Any Opportunistic Infection Within 12 Months
Time Frame: Up to 12 months
Up to 12 months
Percentage of Participants With Post-Transplant Diabetes Mellitus
Time Frame: Up to 12 months
Up to 12 months
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).
Up to 12 months
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.
From Month 24 to Month 84
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.
From Month 24 to Month 84
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).
From Month 24 to Month 84
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.
From Month 24 to Month 84
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).
From Month 24 to Month 84
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.
From Month 24 to Month 84
Percentage of Participants Surviving at Month 24 and Every 12 Months up to Month 84
Time Frame: From Month 24 to Month 84
From Month 24 to Month 84
Number of Participants Who Died From Months 24 to Month 84
Time Frame: From Month 24 to Month 84
From Month 24 to Month 84
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
From Month 24 to Month 84
Number of Participants Who Had Lost Their Transplant up to Month 84
Time Frame: From Month 24 to Month 84
From Month 24 to Month 84
Number of Participants With Active CMV Infection Who Had Lost Their Transplant up to Month 84
Time Frame: From Month 24 to Month 84
From Month 24 to Month 84
Number of Participants Without Active CMV Infection Who Had Lost Their Transplant up to Month 84
Time Frame: From Month 24 to Month 84
From Month 24 to Month 84
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).
Up to 84 months
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).
Up to 84 months
Number of Participants Who Had Lost Their Transplant or Died up to Month 84
Time Frame: From Month 24 to Month 84
From Month 24 to Month 84
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
From Month 24 to Month 84
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
From Month 24 to Month 84
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
From Month 24 to Month 84
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.
From Month 24 to Month 84

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hoffmann-La Roche

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2006

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 5, 2006

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 5, 2006

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 6, 2006

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 11, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 26, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ML19313

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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