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Trial registered on ANZCTR


Registration number
ACTRN12610000016033
Ethics application status
Approved
Date submitted
23/12/2009
Date registered
26/09/2007
Date last updated
15/01/2019
Date data sharing statement initially provided
15/01/2019
Date results information initially provided
15/01/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
The 2VAL Study: A trial comparing the effect of valacyclovir and valganciclovir prophylaxis against cytomegalovirus (CMV) infection after renal transplantation
Scientific title
Randomized trial comparing valacyclovir versus valganciclovir prophylaxis of cytomegalovirus infection in renal transplant recipients
Secondary ID [1] 1060 0
CRG090700119
Cochrane Renal Group
Universal Trial Number (UTN)
Trial acronym
The 2VAL Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cytomegalovirus infection after renal transplantation 243775 0
Condition category
Condition code
Infection 256607 256607 0 0
Studies of infection and infectious agents
Renal and Urogenital 256644 256644 0 0
Kidney disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Oral valacyclovir (VALTREX, Glaxo Wellcome) 8g/day for 3 months after transplantation started within 1 week post transplant
Intervention code [1] 255733 0
Treatment: Drugs
Intervention code [2] 255774 0
Prevention
Comparator / control treatment
Oral valganciclovir (VALCYTE, Roche) 900mg/day for 3 months after transplantation started within 1 week post transplant
Control group
Active

Outcomes
Primary outcome [1] 240844 0
Active cytomegalovirus (CMV) infection (DNAemia = presence of CMV viremia by quantitative polymerase chain reaction (PCR) for CMV deoxyribonucleic acid (DNA) test )
Timepoint [1] 240844 0
12 months post transplant
Primary outcome [2] 257501 0
Biopsy-proven acute rejection
Timepoint [2] 257501 0
12 months post transplant
Primary outcome [3] 257502 0
Incidence and severity of interstitial fibrosis and tubular atrophy (IF/TA) assesed at Months 36 protocol biopsy
Timepoint [3] 257502 0
36 months post transplant
Secondary outcome [1] 257514 0
Cumulative incidence of CMV disease, defined by clinical symptoms + presence of CMV viremia by quantitative polymerase chain reaction (PCR) for CMV deoxyribonucleic acid (DNA) test
Timepoint [1] 257514 0
12 and 36 months post transplant
Secondary outcome [2] 262710 0
Presumed and clinical acute rejection assessed by laboratory tests (renal function impairement) and renal allograft biopsy with the inclusion of histologic findings of "borderline rejection"
Timepoint [2] 262710 0
12 months post transplant
Secondary outcome [3] 262711 0
Subclinical acute rejection at Months 3 protocol biopsy
Timepoint [3] 262711 0
3 months post transplant
Secondary outcome [4] 262712 0
IF/TA and chronic rejection at Months 3 protocol biopsy
Timepoint [4] 262712 0
3 months post transplant
Secondary outcome [5] 262713 0
Level of CMV specific CD4 and CD8 T-lymphocyte immune response assessed by blood analysis
Timepoint [5] 262713 0
12 months post transplant
Secondary outcome [6] 262714 0
Lymphocyte function before and after withdrawal of antivirotics assessed by blood analysis and in vitro lymfocyte stimulation tests
Timepoint [6] 262714 0
3 and 4 months post transplant
Secondary outcome [7] 262715 0
renal function assessed by serum creatinine and estimated glomerular filtration rate
Timepoint [7] 262715 0
12 and 36 months post transplant
Secondary outcome [8] 262716 0
other infections assessed by clinical symptoms, microbiological cultures, blood tests
Timepoint [8] 262716 0
12 and 36 months post transplant
Secondary outcome [9] 262717 0
adverse events based on prospective observation (examples od side effects - heamatological - leukopenia, trombocytopenia, anemia, psychiatric - hallucinations+confusion, liver enzyme abnormalities, de novo post transplant diabetes, de novo malignancy, etc.)
Timepoint [9] 262717 0
12 months post transplant
Secondary outcome [10] 262718 0
Cumulative patient and graft survival based on prospective observation
Timepoint [10] 262718 0
12 and 36 months post transplant
Secondary outcome [11] 262719 0
Costs related to CMV management based on prospective resource data collection
Timepoint [11] 262719 0
12 months post transplant
Secondary outcome [12] 262720 0
Messenger ribonucleic acid (mRNA) expression of selected cytokines in renal tissue at Months 36 protocol biopsy
Timepoint [12] 262720 0
36 months post transplant
Secondary outcome [13] 262721 0
Chronic allograft rejection (humoral/cellular) - biopsy proven
Timepoint [13] 262721 0
36 months post transplant
Secondary outcome [14] 262722 0
Late acute rejection - biopsy proven
Timepoint [14] 262722 0
36 months post transplant

Eligibility
Key inclusion criteria
Recipients of transplant from deceased or living donor, known donor (D) and recipient (R) CMV serology before transplantation of D+/R- or D+/R+ or D-/R+, provided informed consent
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Unknown or D-/R- CMV serology prior to transplantation, systemic antiviral drug intake within 2 weeks before transplantation except for hepatitis B therapy (lamivudine, adefovir, entecavir), active viral infection at the time of transplantation (except for hepatitis B or C), significant leukopenia or thrombocytopenia, participation in another clinical trial, known allergy to (val)acyclovir or (val)ganciclovir, inability to provide informed concent

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
All subjects indicated to kidney transplantation were considered for inclusion to the trial prior to transplantation. If the patient met inclusion criteria and signed informed consent randomization occurred. Hidden numbered envelops containing the treatment arm were used. Thus the treatment arm was consealed to the researcher until the patient had been included to the trial.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Random-number table, 1:1 ratio
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 2097 0
Czech Republic
State/province [1] 2097 0

Funding & Sponsors
Funding source category [1] 243677 0
Government body
Name [1] 243677 0
Research Project No. MSM0021620819 awarded by the Ministry of Education, Youth, and Physical Training of the Czech Republic
Address [1] 243677 0
Ministry of Education, Youth, and Physical Training of the Czech Republic, Karmelitska 7, 118 12 Prague, Czech Republic
Country [1] 243677 0
Czech Republic
Funding source category [2] 256207 0
Government body
Name [2] 256207 0
Internal Grant Agency (IGA) Grant NR9267-3 awarded by the Ministry of Health of the Czech Republic
Address [2] 256207 0
Ministry of Health of the Czech Republic,
Palackeho namesti 4,
128 01 Prague
Country [2] 256207 0
Czech Republic
Primary sponsor type
Individual
Name
Tomas Reischig, M.D., Ph.D.
Address
Head of Division of Nephrology, Department of Internal Medicine I Charles University Medical School and Teaching Hospital, alej Svobody 80, 30460 Pilsen Czech Republic
Country
Czech Republic
Secondary sponsor category [1] 251575 0
None
Name [1] 251575 0
Address [1] 251575 0
Country [1] 251575 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 258310 0
Local Ethics Committee of Charles University Medical School and Teaching Hospital in Pilsen
Ethics committee address [1] 258310 0
Local Ethics Committee (director: Prof. J. Finek, M.D., Ph.D.), Charles University Medical School and Teaching Hospital, alej Svobody 80, 304 60 Pilsen, Czech Republic
Ethics committee country [1] 258310 0
Date submitted for ethics approval [1] 258310 0
25/06/2007
Approval date [1] 258310 0
30/07/2007
Ethics approval number [1] 258310 0

Summary
Brief summary
There are two major hypothesis to test:
1) Valacyclovir prophylaxis for cytomegalovirus infection is not inferior than valganciclovir prophylaxis in the prevention of active cytomegalovirus infection and disease.
2) Valacyclovir is superior to valganciclovir in the prevention of indirect effects of cytomegalovirus: acute renal allograft rejection in short term follow up, and renal function and chronic interstitial fibrosis and tubular atrophy (IF/TA) in long-term follow up.
Trial website
not available
Trial related presentations / publications
Reischig T, Prucha M, Sedlackova L, Lysak D, Jindra P, Bouda M, Matejovic M. Valganciclovir prophylaxis against cytomegalovirus impairs lymphocyte proliferation and activation in renal transplant recipients. Antivir Ther 2011, 16: 1227-1235.
Reischig 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, 15(2):294-304.
Kacer M, Kielberger L, Bouda M, Reischig T. Valganciclovir versus valacyclovir prophylaxis for prevention of cytomegalovirus: an economic perspective. Transpl Infect Dis. 2015, 17(3):334-41.
Public notes

Contacts
Principal investigator
Name 30229 0
A/Prof Tomas Reischig
Address 30229 0
Head of Nephrology Division, Internal Medicine I (Division of Nephrology and Transplant Center), Charles University Medical School and Teaching Hospital, Alej Svobody 80, 30460 Pilsen, CZECH REP.
Country 30229 0
Czech Republic
Phone 30229 0
+420377103650
Fax 30229 0
Email 30229 0
reischig@fnplzen.cz
Contact person for public queries
Name 13476 0
A/Prof Tomas Reischig, M.D., Ph.D.
Address 13476 0
Head of Nephrology Division, Internal Medicine I (Division of Nephrology and Transplant Center), Charles University Medical School and Teaching Hospital, Alej Svobody 80, 30460 Pilsen, CZECH REP.
Country 13476 0
Czech Republic
Phone 13476 0
+420377103650
Fax 13476 0
Email 13476 0
reischig@fnplzen.cz
Contact person for scientific queries
Name 4404 0
A/Prof Tomas Reischig, M.D., Ph.D.
Address 4404 0
Head of Nephrology Division, Internal Medicine I (Division of Nephrology and Transplant Center), Charles University Medical School and Teaching Hospital, Alej Svobody 80, 30460 Pilsen, CZECH REP.
Country 4404 0
Czech Republic
Phone 4404 0
+420377103650
Fax 4404 0
Email 4404 0
reischig@fnplzen.cz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
Summary results
Have study results been published in a peer-reviewed journal?
Yes
Journal publication details
Publication date and citation/details [1] 1044 0
Reischig T, Prucha M, Sedlackova L, Lysak D, Jindra P, Bouda M, Matejovic M. Valganciclovir prophylaxis against cytomegalovirus impairs lymphocyte proliferation and activation in renal transplant recipients. Antivir Ther 2011, 16: 1227-1235.
Attachments [1] 1044 0
Publication date and citation/details [2] 1056 0
Reischig 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, 15(2):294-304.
Attachments [2] 1056 0
Publication date and citation/details [3] 1057 0
Kacer M, Kielberger L, Bouda M, Reischig T. Valganciclovir versus valacyclovir prophylaxis for prevention of cytomegalovirus: an economic perspective. Transpl Infect Dis. 2015, 17(3):334-41.
Attachments [3] 1057 0
Publication date and citation/details [4] 1058 0
Reischig T, Kacer M, Hruba P, Hermanova H, Hes O, Lysak D, Kormunda S, Bouda M. Less renal allograft fibrosis with valganciclovir prophylaxis for cytomegalovirus compared to high-dose valacyclovir: a parellel group, open-label, randomized controlled trial. BMC Infect Dis 2018, 18:573.
Attachments [4] 1058 0
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary