search
Back to results

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

Primary Purpose

Infection in Solid Organ Transplant Recipients

Status
Completed
Phase
Phase 4
Locations
Spain
Study Type
Interventional
Intervention
Ganciclovir/ Valganciclovir according to SPC
Ganciclovir/ Valganciclovir according to PK model
Sponsored by
Nuria Lloberas
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Infection in Solid Organ Transplant Recipients focused on measuring Cytomegalovirus, renal transplant

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Nephrology Department- Hospital Universitari Bellvtge

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Experimental

Active Comparator

Experimental

Arm Label

1.A (Prophylaxis-SPC)

1.B (Prophylaxis- PK model)

2.A (Treatment-SPC)

2.B (Treatment-PK model)

Arm Description

Prophylaxis for CMV infection and Ganciclovir/ Valganciclovir doses according to summaries of product characteristics (SPC).

Prophylaxis for CMV infection and Ganciclovir/Valganciclovir doses according to pharmacokinetic model.

Treatment for CMV infection/disease and Ganciclovir/ Valganciclovir doses according to summaries of product characteristics (SPC).

Treatment for CMV infection/disease and Ganciclovir/Valganciclovir doses according to pharmacokinetic model

Outcomes

Primary Outcome Measures

Area under the concentration time curve (AUC)of ganciclovir in steady state
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.

Secondary Outcome Measures

CMV viral load measured by quantitative polymerase chain reaction (PCR)
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)
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)
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)
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)
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.

Full Information

First Posted
September 19, 2011
Last Updated
March 25, 2015
Sponsor
Nuria Lloberas
Collaborators
Ministerio de Sanidad, Servicios Sociales e Igualdad
search

1. Study Identification

Unique Protocol Identification Number
NCT01446445
Brief Title
Individualization of Ganciclovir and Valganciclovir Doses Using Bayesian Prediction in Renal Transplant Patients.
Official Title
Individualization of Ganciclovir and Valganciclovir Doses in Renal Transplant Patients for Prophylaxis or Treatment of Cytomegalovirus(CMV)Infection Using Bayesian Prediction.
Study Type
Interventional

2. Study Status

Record Verification Date
March 2015
Overall Recruitment Status
Completed
Study Start Date
December 2011 (undefined)
Primary Completion Date
August 2014 (Actual)
Study Completion Date
August 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Nuria Lloberas
Collaborators
Ministerio de Sanidad, Servicios Sociales e Igualdad

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infection in Solid Organ Transplant Recipients
Keywords
Cytomegalovirus, renal transplant

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
60 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1.A (Prophylaxis-SPC)
Arm Type
Active Comparator
Arm Description
Prophylaxis for CMV infection and Ganciclovir/ Valganciclovir doses according to summaries of product characteristics (SPC).
Arm Title
1.B (Prophylaxis- PK model)
Arm Type
Experimental
Arm Description
Prophylaxis for CMV infection and Ganciclovir/Valganciclovir doses according to pharmacokinetic model.
Arm Title
2.A (Treatment-SPC)
Arm Type
Active Comparator
Arm Description
Treatment for CMV infection/disease and Ganciclovir/ Valganciclovir doses according to summaries of product characteristics (SPC).
Arm Title
2.B (Treatment-PK model)
Arm Type
Experimental
Arm Description
Treatment for CMV infection/disease and Ganciclovir/Valganciclovir doses according to pharmacokinetic model
Intervention Type
Drug
Intervention Name(s)
Ganciclovir/ Valganciclovir according to SPC
Other Intervention Name(s)
Cymevene and Valcyte doses calculated according to SPC
Intervention Description
Doses according to Summaries of Product Characteristics (SPC)
Intervention Type
Drug
Intervention Name(s)
Ganciclovir/ Valganciclovir according to PK model
Other Intervention Name(s)
Cymevene and Valcyte doses calculated according to PK model
Intervention Description
Doses according to population pharmacokinetic model
Primary Outcome Measure Information:
Title
Area under the concentration time curve (AUC)of ganciclovir in steady state
Description
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.
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.
Secondary Outcome Measure Information:
Title
CMV viral load measured by quantitative polymerase chain reaction (PCR)
Description
CMV viral load will be correlated with the exposure to ganciclovir during treatment period, in both interventions.
Time Frame
Change from baseline to day 30 of study entry
Title
CMV viral load measured by quantitative polymerase chain reaction (PCR)
Description
CMV viral load will be correlated with the exposure to ganciclovir during treatment period, in both interventions.
Time Frame
Change from baseline to day 60 of study entry
Title
CMV viral load measured by quantitative polymerase chain reaction (PCR)
Description
CMV viral load will be correlated with the exposure to ganciclovir during treatment period, in both interventions.
Time Frame
Change from baseline to day 90 of study entry
Title
T-cell immune response against CMV infection measured by Enzyme-linked immunosorbent spot (ELISPOT)
Description
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.
Time Frame
Change from day 40 of treatment to day 20 after end of treatment.
Title
T-cell immune response against CMV infection measured by Enzyme-linked immunosorbent spot (ELISPOT)
Description
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.
Time Frame
Change from baseline to day 20 of treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nuria Lloberas, Ph.D
Organizational Affiliation
Nephrology Department-Hospital Universitari Bellvitge
Official's Role
Principal Investigator
Facility Information:
Facility Name
Nephrology Department- Hospital Universitari Bellvtge
City
L'Hospitalet de Llobregat
State/Province
Barcelona
ZIP/Postal Code
08028
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
26824942
Citation
Padulles A, Colom H, Bestard O, Melilli E, Sabe N, Rigo R, Niubo J, Torras J, Llado L, Manito N, Caldes A, Cruzado JM, Grinyo JM, Lloberas N. Contribution of Population Pharmacokinetics to Dose Optimization of Ganciclovir-Valganciclovir in Solid-Organ Transplant Patients. Antimicrob Agents Chemother. 2016 Mar 25;60(4):1992-2002. doi: 10.1128/AAC.02130-15. Print 2016 Apr.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs