Infection in Solid Organ Transplant RecipientsPhase 4NCT01446445
Individualization of Ganciclovir and Valganciclovir Doses Using Bayesian Prediction in Renal Transplant Patients.
A Phase 4 study testing Ganciclovir/ Valganciclovir according to SPC and Ganciclovir/ Valganciclovir according to PK model in people with Infection in Solid Organ Transplant Recipients, run by Nuria Lloberas at 1 site in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Infection in Solid Organ Transplant Recipients
- What is being tested?
- Ganciclovir/ Valganciclovir according to SPC and Ganciclovir/ Valganciclovir according to PK model
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteSpain
- Study dates
- Dec 2011to Aug 2014
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Spain1 site
Nephrology Department- Hospital Universitari Bellvtge
L'Hospitalet de Llobregat, Barcelona, 08028
About this study
Official title: 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.
Read the 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.
- Being tested
- Ganciclovir/ Valganciclovir according to SPC, Ganciclovir/ Valganciclovir according to PK model
- Keywords
- Cytomegalovirus, renal transplant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ganciclovir/ Valganciclovir according to SPCDrug
Also called Cymevene and Valcyte doses calculated according to SPC
Doses according to Summaries of Product Characteristics (SPC)
Ganciclovir/ Valganciclovir according to PK modelDrug
Also called Cymevene and Valcyte doses calculated according to PK model
Doses according to population pharmacokinetic model
| Study group | Role | What they receive |
|---|---|---|
| 1.A (Prophylaxis-SPC) | Active comparator | Prophylaxis for CMV infection and Ganciclovir/ Valganciclovir doses according to summaries of product characteristics (SPC). Receives: Drug: Ganciclovir/ Valganciclovir according to SPC |
| 1.B (Prophylaxis- PK model) | Experimental | Prophylaxis for CMV infection and Ganciclovir/Valganciclovir doses according to pharmacokinetic model. Receives: Drug: Ganciclovir/ Valganciclovir according to PK model |
| 2.A (Treatment-SPC) | Active comparator | Treatment for CMV infection/disease and Ganciclovir/ Valganciclovir doses according to summaries of product characteristics (SPC). Receives: Drug: Ganciclovir/ Valganciclovir according to SPC |
| 2.B (Treatment-PK model) | Experimental | Treatment for CMV infection/disease and Ganciclovir/Valganciclovir doses according to pharmacokinetic model Receives: Drug: Ganciclovir/ Valganciclovir according to PK model |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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 outcomes (5)
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.
Measured: Change from baseline to day 30 of study entry
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.
Measured: Change from baseline to day 60 of study entry
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.
Measured: Change from baseline to day 90 of study entry
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.
Measured: 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)
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.
Measured: Change from baseline to day 20 of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2011 (estimated)
- Study startDec 2011
- Primary completionAug 2014
- Study completionAug 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Infection in Solid Organ Transplant RecipientsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nuria Lloberas
- Sponsor type
- University, hospital or other
- Collaborators
- Ministerio de Sanidad, Servicios Sociales e Igualdad
- Responsible party
- Sponsor-investigator, Nuria Lloberas, Hospital Universitari de Bellvitge
- Investigators
- Nuria Lloberas, Ph.D, Principal investigator, Nephrology Department-Hospital Universitari Bellvitge
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01446445
- Sponsor's protocol ID
- GCV2010
- Other IDs
- 2010-021433-32
- Status last verified
- Mar 2015
- First submitted
- 19 Sep 2011
- Last updated
- 27 Mar 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 39807668Vernooij 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.
PubMed 38700045Padulles 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.
PubMed 26824942
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Individualization of Ganciclovir and Valganciclovir Doses in Renal Transplant Patients for Prophylaxis or Treatment of Cytomegalovirus(CMV)Infection Using Bayesian Prediction.
- ClinicalTrials.gov ID
- NCT01446445
- Acronym / sponsor ID
- GCV2010
- Keywords
- Cytomegalovirus, renal transplant
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Nuria LloberasUniversity, hospital or other
- Collaborators
- Ministerio de Sanidad, Servicios Sociales e Igualdad
- Study start
- Dec 2011
- Primary completion
- Aug 2014 (actual)
- Study completion
- Aug 2014 (actual)
- First posted
- 5 Oct 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1.A (Prophylaxis-SPC) | Active comparator | Drug: Ganciclovir/ Valganciclovir according to SPCProphylaxis for CMV infection and Ganciclovir/ Valganciclovir doses according to summaries of product characteristics (SPC). |
| 1.B (Prophylaxis- PK model) | Experimental | Drug: Ganciclovir/ Valganciclovir according to PK modelProphylaxis for CMV infection and Ganciclovir/Valganciclovir doses according to pharmacokinetic model. |
| 2.A (Treatment-SPC) | Active comparator | Drug: Ganciclovir/ Valganciclovir according to SPCTreatment for CMV infection/disease and Ganciclovir/ Valganciclovir doses according to summaries of product characteristics (SPC). |
| 2.B (Treatment-PK model) | Experimental | Drug: Ganciclovir/ Valganciclovir according to PK modelTreatment for CMV infection/disease and Ganciclovir/Valganciclovir doses according to pharmacokinetic model |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ganciclovir/ Valganciclovir according to SPCAlso: Cymevene and Valcyte doses calculated according to SPCDoses according to Summaries of Product Characteristics (SPC) | Drug | 1.A (Prophylaxis-SPC), 2.A (Treatment-SPC) |
| Ganciclovir/ Valganciclovir according to PK modelAlso: Cymevene and Valcyte doses calculated according to PK modelDoses according to population pharmacokinetic model | Drug | 1.B (Prophylaxis- PK model), 2.B (Treatment-PK model) |
Primary outcome
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.
5 secondary outcomes
CMV viral load measured by quantitative polymerase chain reaction (PCR)
Time frame: 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 measured by quantitative polymerase chain reaction (PCR)
Time frame: 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.
T-cell immune response against CMV infection measured by Enzyme-linked immunosorbent spot (ELISPOT)
Time frame: Change from baseline to day 20 of treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2015.
- Derived from this study: PubMed 39807668Vernooij 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.
- Derived from this study: PubMed 38700045Vernooij 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.
- Derived from this study: PubMed 26824942Padulles 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nuria Lloberas, Ph.D principal investigator
Nephrology Department-Hospital Universitari Bellvitge
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ganciclovir/ Valganciclovir according to SPC and Ganciclovir/ Valganciclovir according to PK model in people with Infection in Solid Organ Transplant Recipients, run by Nuria Lloberas at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01446445, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2015.