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

NCT ID: NCT01446445

Last Updated: 2015-03-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-12-31
• Study Completion Date: 2014-08-31

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.

Conditions

Infection in Solid Organ Transplant Recipients

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1.A (Prophylaxis-SPC)

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

Group Type: ACTIVE_COMPARATOR

Ganciclovir/ Valganciclovir according to SPC

Intervention Type: DRUG

Doses according to Summaries of Product Characteristics (SPC)

1.B (Prophylaxis- PK model)

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

Group Type: EXPERIMENTAL

Ganciclovir/ Valganciclovir according to PK model

Intervention Type: DRUG

Doses according to population pharmacokinetic model

2.A (Treatment-SPC)

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

Group Type: ACTIVE_COMPARATOR

Ganciclovir/ Valganciclovir according to SPC

Intervention Type: DRUG

Doses according to Summaries of Product Characteristics (SPC)

2.B (Treatment-PK model)

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

Group Type: EXPERIMENTAL

Ganciclovir/ Valganciclovir according to PK model

Intervention Type: DRUG

Doses according to population pharmacokinetic model

Interventions

Ganciclovir/ Valganciclovir according to SPC

Doses according to Summaries of Product Characteristics (SPC)

Intervention Type: DRUG

Ganciclovir/ Valganciclovir according to PK model

Doses according to population pharmacokinetic model

Intervention Type: DRUG

Other Intervention Names

Cymevene and Valcyte doses calculated according to SPC; Cymevene and Valcyte doses calculated according to PK model

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ministerio de Sanidad, Servicios Sociales e Igualdad

OTHER_GOV

Sponsor Role: collaborator

Nuria Lloberas

OTHER

Sponsor Role: lead

Responsible Party

Nuria Lloberas

Clinical Investigator of Nephrology Department

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Nuria Lloberas, Ph.D

Role: PRINCIPAL_INVESTIGATOR

Nephrology Department-Hospital Universitari Bellvitge

Locations

Nephrology Department- Hospital Universitari Bellvtge

L'Hospitalet de Llobregat, Barcelona, Spain

Countries

Spain

References

Vernooij RW, Michael M, Colombijn JM, Owers DS, Webster AC, Strippoli GF, Hodson EM. Pre-emptive treatment for cytomegalovirus viraemia to prevent cytomegalovirus disease in solid organ transplant recipients. Cochrane Database Syst Rev. 2025 Jan 14;1(1):CD005133. doi: 10.1002/14651858.CD005133.pub4.

Reference Type: DERIVED

PMID: 39807668 (View on PubMed)

Vernooij RW, Michael M, Ladhani M, Webster AC, Strippoli GF, Craig JC, Hodson EM. Antiviral medications for preventing cytomegalovirus disease in solid organ transplant recipients. Cochrane Database Syst Rev. 2024 May 3;5(5):CD003774. doi: 10.1002/14651858.CD003774.pub5.

Reference Type: DERIVED

PMID: 38700045 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26824942 (View on PubMed)

Other Identifiers

2010-021433-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GCV2010

Identifier Type: -

Identifier Source: org_study_id