Transplantation InfectionPhase 2NCT01972035
ValGanciclovir Versus ValAcyclovir for Viral Prophylaxis in Kidney Transplantation
A Phase 2 study testing Valacyclovir and Valganciclovir in people with Transplantation Infection and Epstein-Barr Virus Infections, run by University of Minnesota at 1 site in United States.
Trial summary
Our study will compare all kidney transplant recipients receiving valganciclovir vs. valacyclovir for one year following kidney transplant and compare: 1. the incidence, magnitude and duration of CMV and EBV viremia in the first year after transplant. 2. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Transplantation Infection, Epstein-Barr Virus Infections, Cytomegalovirus Infections
- What is being tested?
- Valacyclovir and Valganciclovir
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 137 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Aug 2014to 28 Feb 2021
- Phase
- Phase 2
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- All consenting kidney transplant recipients.
Who cannot join
- Non-consent.
- Recipients with allergies to valacyclovir or valganciclovir
- Recipients that are unable to independently understand the consent form and do not have a legally authorized representative.
Trial locations and contacts
1 site in 1 country.
About this study
Our study will compare all kidney transplant recipients receiving valganciclovir vs. valacyclovir for one year following kidney transplant and compare:
- the incidence, magnitude and duration of CMV and EBV viremia in the first year after transplant.
- the side effects of the anti-viral drugs requiring dose reduction or cessation
In addition, we will test renal tissue obtained from any biopsies post-transplant (surveillance or clinically indicated biopsies) by both polymerase chain reaction (PCR) and fluorescence in situ hybridization to assess for latent CMV and/or EBV.
Read the detailed description
Herpes viruses such as Epstein-Barr virus (EBV) and cytomegalovirus (CMV) cause considerable morbidity and mortality post-kidney transplant. Even subclinical CMV and/or EBV viremia have been associated with deterioration in kidney transplant function. Currently, valganciclovir (valG) is the primary prophylactic agent against CMV in kidney transplant recipients but CMV viremia has been noted in 22% of pediatric post-kidney transplant recipients, and the incidence at the University of Minnesota (UMMC) in all kidney transplant recipients is as high as 17% despite valG prophylaxis. CMV disease post-kidney transplant can manifest as fever, leucopenia, or mild to severe organ involvement. While an effective anti-CMV drug, valG has a number of adverse effects including leucopenia, also a side effect of mycophenolate mofetil (MMF), one of the cornerstones of current anti-rejection regimens. Combined therapy with MMF and valG frequently results in leucopenia associated infection or leucopenia necessitating reduction in MMF doses, increasing the risk of rejection. In addition, valG is prohibitively expensive forcing many centers adopt a pre-emptive therapeutic approach whereby post-Ktx patients are screened for CMV, and at new onset viremia, valG is initiated. This approach has been associated with increased CMV infections and resistant viral strains. Therefore, there is need for an alternate, more cost-effective drug with a more benign side effect profile and equal effectiveness against CMV.
To date, the anti-EBV effect of valG is poorly defined and prevention of EBV infection is by close monitoring and immunosuppression reduction at the discovery of EBV viremia. EBV can present post-kidney transplants as infectious mononucleosis syndrome, hepatitis and, most importantly, can initiate potentially fatal lymphoproliferative disorders (PTLD). Between October 2003 and December 2009, EBV viremia occurred in 20% of adults and 50% of pediatric kidney transplant recipients (60/120) at UMMC, and, PTLD occurred in 6% (7/120) of pediatric recipients. Effective anti-EBV prophylaxis could substantially improve kidney transplant outcomes.
UMMC conducts surveillance biopsies at transplant and 3 and 12 months post-kidney transplant on all adult transplant recipients, providing an ideal opportunity to assess kidney tissue for EBV and CMV via molecular and immunological assays. Isolating the virus from infected recipient would be a pivotal step in our understanding of the mechanisms of CMV and EBV infection post-kidney transplant.
In summary, if valacyclovir and valganciclovir have equivalent efficacy in CMV prophylaxis, and valacyclovir has the anticipated effect on EBV prevention, the use of valacyclovir will result in a reduced risk of leucopenia-associated infection, and a lower incidence of rejection by allowing the use of standard MMF doses. Since valacyclovir is cheaper, it is plausible that universal prophylaxis will be a plausible and affordable option for all transplant recipients.
- Being tested
- Valacyclovir, Valganciclovir
- Keywords
- EBV, CMV, Kidney transplant, valganciclovir, valacyclovir
- Medical subject headings
- Epstein-Barr Virus Infections, Cytomegalovirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ValacyclovirDrug
Also called Valtrex, Valacyclovir Hydrochloride, Valacyclovir HCL
Experimental Arm
ValganciclovirDrug
Also called Valcyte, Valganciclovir hydrochloride
Standard of care
| Study group | Role | What they receive |
|---|---|---|
| ValAcyclovir | Experimental | Kidney recipients who give informed consent will be randomly assigned to receive ValA or ValG in a 1:1 ratio. Duration of therapy is 3-12 months depending on risk and age of recipient. Dosing is based on glomerular filtration rate. Receives: Drug: Valacyclovir |
| ValGanciclovir | Active comparator | Kidney recipients who give informed consent will be randomly assigned to receive ValG or ValA in a 1:1 ratio. Duration of therapy is 3-12 months depending on risk and age of recipient. Dosing is based on glomerular filtration rate. Receives: Drug: Valganciclovir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Compare Incidence, Duration and Magnitude of CMV and EBV Viremia in Kidney Transplant Recipients Receiving valA vs. valG.
In infectious mononucleosis intervention trials, two weeks of valA therapy resulted in a statistically significant reduction in oral EBV shedding, accompanied by a clinical benefit, and valA is currently used for the therapy of severe cases of infectious mononucleosis in the community. ValA has also been shown to reduce the incidence and delay the onset of CMV disease in both CMV seronegative patients (P<0.001) and CMV seropositive patients (P=0.03). Therefore we hypothesize that the anti-EBV and anti-CMV effects of valA will be equal to or more effective than valG in reducing post-kidney transplant EBV and CMV viremia.
Measured: First year post-kidney transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2013 (estimated)
- Study start1 Aug 2014
- Primary completion28 Feb 2021
- Study completion28 Feb 2021
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 (2)Papers the sponsor has linked to this study.
- Other trials for Transplantation InfectionStudies of the same condition, open and under way.
- More trials run by University of MinnesotaThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 137 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Hank Balfour, MD, Principal investigator, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01972035
- Sponsor's protocol ID
- 130162
- Status last verified
- Mar 2022
- First submitted
- 10 Oct 2013
- Last updated
- 12 Apr 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Kacer M, Kielberger L, Bouda M, Reischig T. Valganciclovir versus valacyclovir prophylaxis for prevention of cytomegalovirus: an economic perspective. Transpl Infect Dis. 2015 Jun;17(3):334-41. doi: 10.1111/tid.12383. Epub 2015 May 26.
PubMed 25824586Reischig T, Kacer M, Jindra P, Hes O, Lysak D, Bouda M. Randomized trial of valganciclovir versus valacyclovir prophylaxis for prevention of cytomegalovirus in renal transplantation. Clin J Am Soc Nephrol. 2015 Feb 6;10(2):294-304. doi: 10.2215/CJN.07020714. Epub 2014 Nov 25.
PubMed 25424991
Study at a glance
From the registry record, last updated by the sponsor on 12 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ValGanciclovir Versus ValAcyclovir for Viral Prophylaxis in Kidney Transplantation
- ClinicalTrials.gov ID
- NCT01972035
- Acronym / sponsor ID
- 130162
- Keywords
- EBV, CMV, Kidney transplant, valganciclovir, valacyclovir
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 137 participants (actual)
- Lead sponsor
- University of MinnesotaUniversity, hospital or other
- Study start
- 1 Aug 2014 (actual)
- Primary completion
- 28 Feb 2021 (actual)
- Study completion
- 28 Feb 2021 (actual)
- First posted
- 30 Oct 2013 (estimated)
- Results
- Posted 16 Mar 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Our study will compare all kidney transplant recipients receiving valganciclovir vs. valacyclovir for one year following kidney transplant and compare:
- the incidence, magnitude and duration of CMV and EBV viremia in the first year after transplant.
- the side effects of the anti-viral drugs requiring dose reduction or cessation
In addition, we will test renal tissue obtained from any biopsies post-transplant (surveillance or clinically indicated biopsies) by both polymerase chain reaction (PCR) and fluorescence in situ hybridization to assess for latent CMV and/or EBV.
Detailed description
Herpes viruses such as Epstein-Barr virus (EBV) and cytomegalovirus (CMV) cause considerable morbidity and mortality post-kidney transplant. Even subclinical CMV and/or EBV viremia have been associated with deterioration in kidney transplant function. Currently, valganciclovir (valG) is the primary prophylactic agent against CMV in kidney transplant recipients but CMV viremia has been noted in 22% of pediatric post-kidney transplant recipients, and the incidence at the University of Minnesota (UMMC) in all kidney transplant recipients is as high as 17% despite valG prophylaxis. CMV disease post-kidney transplant can manifest as fever, leucopenia, or mild to severe organ involvement. While an effective anti-CMV drug, valG has a number of adverse effects including leucopenia, also a side effect of mycophenolate mofetil (MMF), one of the cornerstones of current anti-rejection regimens. Combined therapy with MMF and valG frequently results in leucopenia associated infection or leucopenia necessitating reduction in MMF doses, increasing the risk of rejection. In addition, valG is prohibitively expensive forcing many centers adopt a pre-emptive therapeutic approach whereby post-Ktx patients are screened for CMV, and at new onset viremia, valG is initiated. This approach has been associated with increased CMV infections and resistant viral strains. Therefore, there is need for an alternate, more cost-effective drug with a more benign side effect profile and equal effectiveness against CMV.
To date, the anti-EBV effect of valG is poorly defined and prevention of EBV infection is by close monitoring and immunosuppression reduction at the discovery of EBV viremia. EBV can present post-kidney transplants as infectious mononucleosis syndrome, hepatitis and, most importantly, can initiate potentially fatal lymphoproliferative disorders (PTLD). Between October 2003 and December 2009, EBV viremia occurred in 20% of adults and 50% of pediatric kidney transplant recipients (60/120) at UMMC, and, PTLD occurred in 6% (7/120) of pediatric recipients. Effective anti-EBV prophylaxis could substantially improve kidney transplant outcomes.
UMMC conducts surveillance biopsies at transplant and 3 and 12 months post-kidney transplant on all adult transplant recipients, providing an ideal opportunity to assess kidney tissue for EBV and CMV via molecular and immunological assays. Isolating the virus from infected recipient would be a pivotal step in our understanding of the mechanisms of CMV and EBV infection post-kidney transplant.
In summary, if valacyclovir and valganciclovir have equivalent efficacy in CMV prophylaxis, and valacyclovir has the anticipated effect on EBV prevention, the use of valacyclovir will result in a reduced risk of leucopenia-associated infection, and a lower incidence of rejection by allowing the use of standard MMF doses. Since valacyclovir is cheaper, it is plausible that universal prophylaxis will be a plausible and affordable option for all transplant recipients.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ValAcyclovir | Experimental | Drug: ValacyclovirKidney recipients who give informed consent will be randomly assigned to receive ValA or ValG in a 1:1 ratio. Duration of therapy is 3-12 months depending on risk and age of recipient. Dosing is based on glomerular filtration rate. |
| ValGanciclovir | Active comparator | Drug: ValganciclovirKidney recipients who give informed consent will be randomly assigned to receive ValG or ValA in a 1:1 ratio. Duration of therapy is 3-12 months depending on risk and age of recipient. Dosing is based on glomerular filtration rate. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- All consenting kidney transplant recipients.
Key exclusion criteria (3 listed)
- Non-consent.
- Recipients with allergies to valacyclovir or valganciclovir
- Recipients that are unable to independently understand the consent form and do not have a legally authorized representative.
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 |
|---|---|---|
| ValacyclovirAlso: Valtrex, Valacyclovir Hydrochloride, Valacyclovir HCLExperimental Arm | Drug | ValAcyclovir |
| ValganciclovirAlso: Valcyte, Valganciclovir hydrochlorideStandard of care | Drug | ValGanciclovir |
Primary outcome
Compare Incidence, Duration and Magnitude of CMV and EBV Viremia in Kidney Transplant Recipients Receiving valA vs. valG.
Time frame: First year post-kidney transplant
In infectious mononucleosis intervention trials, two weeks of valA therapy resulted in a statistically significant reduction in oral EBV shedding, accompanied by a clinical benefit, and valA is currently used for the therapy of severe cases of infectious mononucleosis in the community. ValA has also been shown to reduce the incidence and delay the onset of CMV disease in both CMV seronegative patients (P<0.001) and CMV seropositive patients (P=0.03). Therefore we hypothesize that the anti-EBV and anti-CMV effects of valA will be equal to or more effective than valG in reducing post-kidney transplant EBV and CMV viremia.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 25824586Kacer M, Kielberger L, Bouda M, Reischig T. Valganciclovir versus valacyclovir prophylaxis for prevention of cytomegalovirus: an economic perspective. Transpl Infect Dis. 2015 Jun;17(3):334-41. doi: 10.1111/tid.12383. Epub 2015 May 26.
- Background: PubMed 25424991Reischig T, Kacer M, Jindra P, Hes O, Lysak D, Bouda M. Randomized trial of valganciclovir versus valacyclovir prophylaxis for prevention of cytomegalovirus in renal transplantation. Clin J Am Soc Nephrol. 2015 Feb 6;10(2):294-304. doi: 10.2215/CJN.07020714. Epub 2014 Nov 25.
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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.
Hank Balfour, MD principal investigator
University of Minnesota
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Valacyclovir and Valganciclovir in people with Transplantation Infection and Epstein-Barr Virus Infections, run by University of Minnesota at 1 site in United States.
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 1 inclusion and 3 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 12 Apr 2022. 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 United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 16 Mar 2022). 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?
Compare Incidence, Duration and Magnitude of CMV and EBV Viremia in Kidney Transplant Recipients Receiving valA vs. valG. (time frame: First year post-kidney transplant). 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 NCT01972035, which also lists 2 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 12 Apr 2022.