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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Hospital Universitari de Bellvitge
Sponsor:
Collaborator:
Ministerio de Sanidad, Servicios Sociales e Igualdad
Information provided by (Responsible Party):
Nuria Lloberas, Hospital Universitari de Bellvitge
ClinicalTrials.gov Identifier:
NCT01446445
First received: September 19, 2011
Last updated: February 14, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Infection in Solid Organ Transplant Recipients
Drug: Ganciclovir/ Valganciclovir according to SPC
Drug: Ganciclovir/ Valganciclovir according to PK model
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Individualization of Ganciclovir and Valganciclovir Doses in Renal Transplant Patients for Prophylaxis or Treatment of Cytomegalovirus(CMV)Infection Using Bayesian Prediction.

Resource links provided by NLM:


Further study details as provided by Hospital Universitari de Bellvitge:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]

    Values of AUC of ganciclovir achieved with each intervention, that is, ganciclovir and valganciclovir dose adjustment according to SPC(specific product charactheristics) 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.



Secondary Outcome Measures:
  • CMV viral load measured by quantitative polymerase chain reaction (PCR) [ Time Frame: Change from baseline to day 30 of study entry ] [ Designated as safety issue: No ]
    CMV viral load will be correlated with the exposure to ganciclovir during treatment period, in both interventions.

  • CMV viral load measured by quantitative polymerase chain reaction (PCR) [ Time Frame: Change from baseline to day 60 of study entry ] [ Designated as safety issue: No ]
    CMV viral load will be correlated with the exposure to ganciclovir during treatment period, in both interventions.

  • CMV viral load measured by quantitative polymerase chain reaction (PCR) [ Time Frame: Change from baseline to day 90 of study entry ] [ Designated as safety issue: No ]
    CMV viral load will be correlated with the exposure to ganciclovir during treatment period, in both interventions.

  • 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. ] [ Designated as safety issue: No ]
    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.

  • T-cell immune response against CMV infection measured by Enzyme-linked immunosorbent spot (ELISPOT) [ Time Frame: Change from baseline to day 20 of treatment ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 50
Study Start Date: December 2011
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1.A (Prophylaxis-SPC)
Prophylaxis for CMV infection and Ganciclovir/ Valganciclovir doses according to summaries of product characteristics (SPC).
Drug: Ganciclovir/ Valganciclovir according to SPC
Doses according to Summaries of Product Characteristics (SPC)
Other Name: 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.
Drug: Ganciclovir/ Valganciclovir according to PK model
Doses according to population pharmacokinetic model
Other Name: 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).
Drug: Ganciclovir/ Valganciclovir according to SPC
Doses according to Summaries of Product Characteristics (SPC)
Other Name: 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
Drug: Ganciclovir/ Valganciclovir according to PK model
Doses according to population pharmacokinetic model
Other Name: Cymevene and Valcyte doses calculated according to PK model

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01446445

Locations
Spain
Nephrology Department- Hospital Universitari Bellvtge Recruiting
L'Hospitalet de Llobregat, Barcelona, Spain, 08028
Contact: Nuria Lloberas, PhD    003493403586    nlloberas@ub.edu   
Principal Investigator: Nuria Lloberas, PhD         
Sponsors and Collaborators
Nuria Lloberas
Ministerio de Sanidad, Servicios Sociales e Igualdad
Investigators
Principal Investigator: Nuria Lloberas, Ph.D Nephrology Department-Hospital Universitari Bellvitge
  More Information

No publications provided

Responsible Party: Nuria Lloberas, Clinical Investigator of Nephrology Department, Hospital Universitari de Bellvitge
ClinicalTrials.gov Identifier: NCT01446445     History of Changes
Other Study ID Numbers: GCV2010, 2010-021433-32
Study First Received: September 19, 2011
Last Updated: February 14, 2014
Health Authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios

Keywords provided by Hospital Universitari de Bellvitge:
Cytomegalovirus
renal transplant

Additional relevant MeSH terms:
Ganciclovir
Valganciclovir
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 24, 2014