Individualization of Ganciclovir and Valganciclovir Doses Using Bayesian Prediction in Renal Transplant Patients.

March 25, 2015 updated by: Nuria Lloberas

Individualization of Ganciclovir and Valganciclovir Doses in Renal Transplant Patients for Prophylaxis or Treatment of Cytomegalovirus(CMV)Infection Using Bayesian Prediction.

The objective of the present study is to optimize intravenous ganciclovir(GCV) and oral valganciclovir (VGCV)doses, advised by the drug exposure, indicated by the area under the concentration time curve (AUC), in renal transplant patients receiving oral VGCV or intravenous GCV for CMV prophylaxis or treatment. The initial doses will be calculated according to population pharmacokinetic model. Subsequent doses will be adjusted according to plasma GCV concentrations, using the Bayesian approach. This method of dose adjustments could lead to increase the percentage of patients achieving a therapeutic exposure.

Study Overview

Detailed Description

The area under the concentration time curve of serum concentrations of GCV is an indicator of systemic exposure to the drug and is related to the effectiveness and safety. According to the population model developed by our group, less than 16% of patients treated achieve the therapeutic goal of AUC (40 to 50 mcg • h / L) after drug dosing according to summary of product characteristics (SPC). Especially, patients with impaired renal function values (creatinine clearance (CrC)l <30 ml / min) or high (CrCl> 70 ml / min) would be overdosed and underdosed, respectively, with the risk of more adverse effects or therapeutic failure.

Therefore, the individualization of the dosage of GCV, can contribute greatly to achieve optimal exposure to the drug in transplant patients, especially in the cases of extreme values of renal function (CrCl decreased and high). As a consequence, minimize adverse effects, ensure greater efficiency in the target population and reduce associated costs.

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Phase 4

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

    • Barcelona
      • L'Hospitalet de Llobregat, Barcelona, Spain, 08028
        • Nephrology Department- Hospital Universitari Bellvtge

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

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Subjects must be 18 or older, weigh more than 34kg and may be of either sex and race.
  • Subjects must be willing to give informed consent (IC) in writing and be able to do and follow the study. If a subject cannot give informed consent in writing , a legal representative could sign in his place.
  • Women of childbearing potential should perform a pregnancy test at the time of entry and accept the use of a medically acceptable contraceptive method during the study.

Exclusion Criteria:

  • Creatinine Clearance (CrCl )<10 mL / min.
  • Subjects may not have a history of type I hypersensitivity or idiosyncratic reactions to drugs ganciclovir/valganciclovir
  • Pregnancy women.
  • Women breast feeding
  • Subjects may not present at time of inclusion any clinically significant disease that could interfere with study evaluations.
  • Previous participation in another clinical trial sponsored by pharmaceutical industry, in which the promoter and the protocol set which should be the treatment for CMV.

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: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 1.A (Prophylaxis-SPC)
Prophylaxis for CMV infection and Ganciclovir/ Valganciclovir doses according to summaries of product characteristics (SPC).
Doses according to Summaries of Product Characteristics (SPC)
Other Names:
  • Cymevene and Valcyte doses calculated according to SPC
Experimental: 1.B (Prophylaxis- PK model)
Prophylaxis for CMV infection and Ganciclovir/Valganciclovir doses according to pharmacokinetic model.
Doses according to population pharmacokinetic model
Other Names:
  • Cymevene and Valcyte doses calculated according to PK model
Active Comparator: 2.A (Treatment-SPC)
Treatment for CMV infection/disease and Ganciclovir/ Valganciclovir doses according to summaries of product characteristics (SPC).
Doses according to Summaries of Product Characteristics (SPC)
Other Names:
  • Cymevene and Valcyte doses calculated according to SPC
Experimental: 2.B (Treatment-PK model)
Treatment for CMV infection/disease and Ganciclovir/Valganciclovir doses according to pharmacokinetic model
Doses according to population pharmacokinetic model
Other Names:
  • Cymevene and Valcyte doses calculated according to PK model

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Area under the concentration time curve (AUC)of ganciclovir in steady state
Time Frame: Change from baseline to the end of the treatment, with an expected average of treatment of 4 weeks in treatment and 90 days in prophylaxis patients.

Values of AUC of ganciclovir achieved with each intervention, that is, ganciclovir and valganciclovir dose adjustment according to SPC(specific product characteristics) or PK (pharmacokinetic) model.

In each intervention: after starting treatment, change in route of administration, change in renal clearance >10 mL/min and end of treatment blood sampling for pharmacokinetic analysis will be performed in order to calculate AUC.

Change from baseline to the end of the treatment, with an expected average of treatment of 4 weeks in treatment and 90 days in prophylaxis patients.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
CMV viral load measured by quantitative polymerase chain reaction (PCR)
Time Frame: Change from baseline to day 30 of study entry
CMV viral load will be correlated with the exposure to ganciclovir during treatment period, in both interventions.
Change from baseline to day 30 of study entry
CMV viral load measured by quantitative polymerase chain reaction (PCR)
Time Frame: Change from baseline to day 60 of study entry
CMV viral load will be correlated with the exposure to ganciclovir during treatment period, in both interventions.
Change from baseline to day 60 of study entry
CMV viral load measured by quantitative polymerase chain reaction (PCR)
Time Frame: Change from baseline to day 90 of study entry
CMV viral load will be correlated with the exposure to ganciclovir during treatment period, in both interventions.
Change from baseline to day 90 of study entry
T-cell immune response against CMV infection measured by Enzyme-linked immunosorbent spot (ELISPOT)
Time Frame: Change from day 40 of treatment to day 20 after end of treatment.
In prophylaxis patients(arm 1.A and 1.B): ELISPOT assay will be performed to assess the immune response to CMV viral infection on day 40 of initial dose and on day 20 after end of prophylactic therapy.
Change from day 40 of treatment to day 20 after end of treatment.
T-cell immune response against CMV infection measured by Enzyme-linked immunosorbent spot (ELISPOT)
Time Frame: Change from baseline to day 20 of treatment
In treatment patients(arm 2.A and 2.B): ELISPOT assay will be performed to assess the immune response to CMV viral infection at baseline, day 10 and 20 of treatment.
Change from baseline to day 20 of treatment

Collaborators and Investigators

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

Sponsor

Investigators

  • Principal Investigator: Nuria Lloberas, Ph.D, Nephrology Department-Hospital Universitari Bellvitge

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.

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

December 1, 2011

Primary Completion (Actual)

August 1, 2014

Study Completion (Actual)

August 1, 2014

Study Registration Dates

First Submitted

September 19, 2011

First Submitted That Met QC Criteria

October 3, 2011

First Posted (Estimate)

October 5, 2011

Study Record Updates

Last Update Posted (Estimate)

March 27, 2015

Last Update Submitted That Met QC Criteria

March 25, 2015

Last Verified

March 1, 2015

More Information

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.

Clinical Trials on Infection in Solid Organ Transplant Recipients

Clinical Trials on Ganciclovir/ Valganciclovir according to SPC

3
Subscribe