Infection in Solid Organ Transplant RecipientsPhase 4NCT02503982
Valganciclovir Dosing in Pediatric Solid Organ Transplant Recipients
A Phase 4 study testing prophylactic Valganciclovir in people with Infection in Solid Organ Transplant Recipients, run by Rabin Medical Center at 1 site in Israel.
Trial summary
Valganciclovir is extensively used for cytomegalovirus (CMV) infection treatment and prophylaxis after solid organ transplantation (SOT). VGC dosing is problematic in children. valganciclovir has variable absorption and is renally excreted. Read more about this study
- Who is it for?
- Ages Up to 17 years
- Conditions the study is for
- Infection in Solid Organ Transplant Recipients
- What is being tested?
- prophylactic Valganciclovir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteIsrael
- Study dates
- Dec 2014to Aug 2015
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 Up to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- children and adolescents 0-18 years old
- Solid Organ Transplantation admitted after transplantation
- Treatment with prophylactic Valganciclovir
- Glomerular Filtration Rate (GFR) >= 60 mL/min/1.73 m2
Who cannot join
- Treatment with ganciclovir IV
- Glomerular Filtration Rate (GFR) < 60 mL/min/1.73 m2
- Imipenem treatment
- Cluster organ transplanted -
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Valganciclovir Dosing in Pediatric Solid Organ Transplant Recipients - a Prospective Study
Valganciclovir is extensively used for cytomegalovirus (CMV) infection treatment and prophylaxis after solid organ transplantation (SOT). VGC dosing is problematic in children. valganciclovir has variable absorption and is renally excreted. Area Under the Curve (AUC) (0-24) of 40-60 mcg∙h/L is a predictive pharmacokinetic parameter of efficacy and safety. Dosing based on manufacturer recommendations is supra-therapeutic in most cases. A few published dosing algorithms result in AUC out of range.
Objective: To prospectively validate a Valganciclovir administration dosing regimen and compare it to other dosing algorithms.
Methods: Children after SOT at Schneider Children's Medical Center, the largest tertiary pediatric center in Israel, were prospectively studied, starting Dec 2014. The dosing regimen was derived from Seattle Children's Hospital guidelines; 14-16 mg/kg/dose. For impaired renal function, stratified dose reduction was used. Blood was withdrawn at steady state: 2, 5 and 10 hours post dosing. Drug level was analyzed by high pressure liquid chromatography (HPLC).
Read the detailed description
Valganciclovir is a novel drug used extensively as a prophylactic, preemptive and treatment agent for cytomegalovirus (CMV) infection after solid organ transplantation (SOT).
It is the valine ester prodrug of Ganciclovir,has a bioavailability of approximately 60%, which is up to 10-fold higher than oral ganciclovir .
Based on the correlation between the Pharmacokinetic (PK) of VGC and its clinical efficacy found in adult studies, AUC (0-24) of approximately 40-60 mcg∙h/mL has been described as predictive PK parameter of efficacy. Considering the mechanism of action of Valganciclovir , relationships of exposure-efficacy and exposure-safety are expected to be similar in children and adults.
In 2009, a new dosing algorithm incorporating both body surface area (BSA) and renal function was introduced by the manufacturer for infants and young children:
Dose (mg) =7 × BSA × CrCl
Very few studies have evaluated this dosing for infants and young children. In 2010 the FDA published a safety alert confirming the excessively high dosage calculated by the dosing algorithm in children with low body weight, low body surface area, and normal serum creatinine. This type of patient was not routinely observed in the clinical trials used to derive and confirm the pediatric dose.
As the body weight decreases and/or as the Creatinine Clearance (CrCl) increases excessively high doses are calculated. There is unproportional variability of doses calculated by the algorithm for infants and young children with normal renal function.
Doses can reach as high as 4 fold higher than the weight-based common dosing.
Objective:
- To prospectively validate a dosing regimen of Valganciclovir administration
- and to compare it to other dosing algorithms.
Methods:
This is a prospective study of all pediatric SOT recipients who were treated with oral valganciclovir. The common practice dose at Schneider Children's Medical Center dosing guidelines of valganciclovir is 17 mg/kg once daily for prophylaxis, with stratified dose reductions for impaired renal function as shown in the table. Max dose was 900 mg.
Measurement of valganciclovir levels After three days of consistent oral dosing to ensure steady-state concentrations, drug levels were measured at 2, 5 and 10 h following administration of the dose, and were analyzed at the pharmacologic laboratory of "Asaf HaRofeh Medical Center" using standard HPLC, with a lower limit of detection of 0.5 mcg/mL and a coefficient of variation of <10%. AUCs were calculated using the trapezoidal method.
- Being tested
- prophylactic Valganciclovir
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
prophylactic ValganciclovirDrug
Also called Valcyte
The common practice dose at Schneider Children's Medical Center dosing guidelines of valganciclovir is 17 mg/kg once daily for prophylaxis, with stratified dose reductions for impaired renal function. Max dose was 900 mg.
| Study group | Role | What they receive |
|---|---|---|
| Solid Organ Transplanted children | Experimental | Intervention: treatment with prophylactic oral valganciclovir with a fixed dose of 17 mg/kg once daily for prophylaxis, and stratified dose reductions for impaired renal function. Max dose was 900 mg. Receives: Drug: prophylactic Valganciclovir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area Under the Curve (AUC)
Valganciclovir area under the curve (AUC) calculated with the trapezoidal method using drug levels measured at 2, 5 and 10 h, and extrapolated beyond the 10 hour time point to arrive at a 24-hour curve.
Measured: drug levels measured at 2, 5 and 10 h following administration of the dose on day 4 creating a 24 hours curve
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2015 (estimated)
- Study startDec 2014
- Primary completionAug 2015
- Study completionAug 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)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
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rabin Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Liat Ashkenazy-Hofnung, MD, Principal investigator, Schneider's Children Medical center of Isreal
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02503982
- Sponsor's protocol ID
- 001-14-RMC
- Status last verified
- Apr 2016
- First submitted
- 14 Jul 2015
- Last updated
- 4 Apr 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Peled O, Berkovitch M, Rom E, Bilavsky E, Bernfeld Y, Dorfman L, Pappo A, Ziv-Baran T, Brandriss N, Bar-Haim A, Amir J, Ashkenazi-Hoffnung L. Valganciclovir Dosing for Cytomegalovirus Prophylaxis in Pediatric Solid-organ Transplant Recipients: A Prospective Pharmacokinetic Study. Pediatr Infect Dis J. 2017 Aug;36(8):745-750. doi: 10.1097/INF.0000000000001595.
PubMed 28383392
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Valganciclovir Dosing in Pediatric Solid Organ Transplant Recipients - a Prospective Study
- ClinicalTrials.gov ID
- NCT02503982
- Acronym / sponsor ID
- 001-14-RMC
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Rabin Medical CenterUniversity, hospital or other
- Study start
- Dec 2014
- Primary completion
- Aug 2015 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 21 Jul 2015 (estimated)
- Results
- Posted 30 Jun 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Valganciclovir is extensively used for cytomegalovirus (CMV) infection treatment and prophylaxis after solid organ transplantation (SOT). VGC dosing is problematic in children. valganciclovir has variable absorption and is renally excreted. Area Under the Curve (AUC) (0-24) of 40-60 mcg∙h/L is a predictive pharmacokinetic parameter of efficacy and safety. Dosing based on manufacturer recommendations is supra-therapeutic in most cases. A few published dosing algorithms result in AUC out of range.
Objective: To prospectively validate a Valganciclovir administration dosing regimen and compare it to other dosing algorithms.
Methods: Children after SOT at Schneider Children's Medical Center, the largest tertiary pediatric center in Israel, were prospectively studied, starting Dec 2014. The dosing regimen was derived from Seattle Children's Hospital guidelines; 14-16 mg/kg/dose. For impaired renal function, stratified dose reduction was used. Blood was withdrawn at steady state: 2, 5 and 10 hours post dosing. Drug level was analyzed by high pressure liquid chromatography (HPLC).
Detailed description
Valganciclovir is a novel drug used extensively as a prophylactic, preemptive and treatment agent for cytomegalovirus (CMV) infection after solid organ transplantation (SOT).
It is the valine ester prodrug of Ganciclovir,has a bioavailability of approximately 60%, which is up to 10-fold higher than oral ganciclovir .
Based on the correlation between the Pharmacokinetic (PK) of VGC and its clinical efficacy found in adult studies, AUC (0-24) of approximately 40-60 mcg∙h/mL has been described as predictive PK parameter of efficacy. Considering the mechanism of action of Valganciclovir , relationships of exposure-efficacy and exposure-safety are expected to be similar in children and adults.
In 2009, a new dosing algorithm incorporating both body surface area (BSA) and renal function was introduced by the manufacturer for infants and young children:
Dose (mg) =7 × BSA × CrCl
Very few studies have evaluated this dosing for infants and young children. In 2010 the FDA published a safety alert confirming the excessively high dosage calculated by the dosing algorithm in children with low body weight, low body surface area, and normal serum creatinine. This type of patient was not routinely observed in the clinical trials used to derive and confirm the pediatric dose.
As the body weight decreases and/or as the Creatinine Clearance (CrCl) increases excessively high doses are calculated. There is unproportional variability of doses calculated by the algorithm for infants and young children with normal renal function.
Doses can reach as high as 4 fold higher than the weight-based common dosing.
Objective:
- To prospectively validate a dosing regimen of Valganciclovir administration
- and to compare it to other dosing algorithms.
Methods:
This is a prospective study of all pediatric SOT recipients who were treated with oral valganciclovir. The common practice dose at Schneider Children's Medical Center dosing guidelines of valganciclovir is 17 mg/kg once daily for prophylaxis, with stratified dose reductions for impaired renal function as shown in the table. Max dose was 900 mg.
Measurement of valganciclovir levels After three days of consistent oral dosing to ensure steady-state concentrations, drug levels were measured at 2, 5 and 10 h following administration of the dose, and were analyzed at the pharmacologic laboratory of "Asaf HaRofeh Medical Center" using standard HPLC, with a lower limit of detection of 0.5 mcg/mL and a coefficient of variation of <10%. AUCs were calculated using the trapezoidal method.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Solid Organ Transplanted children | Experimental | Drug: prophylactic ValganciclovirIntervention: treatment with prophylactic oral valganciclovir with a fixed dose of 17 mg/kg once daily for prophylaxis, and stratified dose reductions for impaired renal function. Max dose was 900 mg. |
Who may qualify
- Ages
- Up to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- children and adolescents 0-18 years old
- Solid Organ Transplantation admitted after transplantation
- Treatment with prophylactic Valganciclovir
- Glomerular Filtration Rate (GFR) >= 60 mL/min/1.73 m2
Key exclusion criteria (4 listed)
- Treatment with ganciclovir IV
- Glomerular Filtration Rate (GFR) < 60 mL/min/1.73 m2
- Imipenem treatment
- Cluster organ transplanted -
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 |
|---|---|---|
| prophylactic ValganciclovirAlso: ValcyteThe common practice dose at Schneider Children's Medical Center dosing guidelines of valganciclovir is 17 mg/kg once daily for prophylaxis, with stratified dose reductions for impaired renal function. Max dose was 900 mg. | Drug | Solid Organ Transplanted children |
Primary outcome
Area Under the Curve (AUC)
Time frame: drug levels measured at 2, 5 and 10 h following administration of the dose on day 4 creating a 24 hours curve
Valganciclovir area under the curve (AUC) calculated with the trapezoidal method using drug levels measured at 2, 5 and 10 h, and extrapolated beyond the 10 hour time point to arrive at a 24-hour curve.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28383392Peled O, Berkovitch M, Rom E, Bilavsky E, Bernfeld Y, Dorfman L, Pappo A, Ziv-Baran T, Brandriss N, Bar-Haim A, Amir J, Ashkenazi-Hoffnung L. Valganciclovir Dosing for Cytomegalovirus Prophylaxis in Pediatric Solid-organ Transplant Recipients: A Prospective Pharmacokinetic Study. Pediatr Infect Dis J. 2017 Aug;36(8):745-750. doi: 10.1097/INF.0000000000001595.
- Individual participant dataSharing planned: No
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RecruitingObservational study
The Organ Transplant Recipient HPV and Skin Cancer Study
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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.
Liat Ashkenazy-Hofnung, MD principal investigator
Schneider's Children Medical center of Isreal
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 prophylactic Valganciclovir in people with Infection in Solid Organ Transplant Recipients, run by Rabin Medical Center at 1 site in Israel.
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 4 inclusion and 4 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 4 Apr 2017. 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 Israel. 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?
Yes. Results are posted in the registry (first posted 30 Jun 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 Curve (AUC) (time frame: drug levels measured at 2, 5 and 10 h following administration of the dose on day 4 creating a 24 hours curve). 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 NCT02503982, which also lists 1 linked publication.
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 4 Apr 2017; AzTrials last refreshed its copy on 7 Nov 2026.