Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
IVIST01
Study information
Scientific title
A monocentre, randomised, open-labeled study to steer immunosuppressive and antiviral therapy by measurement of virus (cytomegalovirus [CMV], adenovirus [ADV], herpes simplex virus [HSV]) specific T-cells in addition to determination of trough levels of immunosuppressants in paediatric kidney and liver allograft recipients: an explorative study
Acronym
IVIST
Study hypothesis
Monitoring of virus-specific T-cells followed by therapeutic intervention can prolong kidney function and reduce viral infections after solid organ transplantation.
Ethics approval
Ethics Committee of the Medical School of Hannover, 21/11/2008, ref: 5067
Study design
Monocentre randomised open-label study
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Paediatric kidney transplantation
Intervention
Antiviral prophylaxis and management should be based on the individual risk assessed by the amount of virus-specific T-cells. Immunosuppressive therapy should be adopted due to the levels of virus-specific T-cells as a direct measure of the intensity of immunosuppression in comparison to classical trough-level monitoring. Patients should be randomised prospectively in a group with monitoring of virus-specific T-cells and in a group that is treated conservatively.
The immunosuppressive therapy will be steered in all patients by classical serum-drug levels. In the intervention group, the relative percentage of virus-specific T-cells will be detected. In case of high levels (50% above the average detected in step 1) the dose of immunosuppression will be increased 20%, in case of low levels (50% below the average detected in step 1), the dose of immunosuppression will be decreased 20%.
In the non-intervention group, valganciclovir will be administered for 3 months, starting at time of transplantation in CMV-IgG negative children who receive an organ from a CMV IgG positive donor. Valganciclovir will also be given in case of CMV infection or reactivation for 3 months. In the intervention group, valganciclovir will only be administered prophylactically in CMV-IgG negative children who receive an organ from a CMV IgG positive donor and who do not have any CMV-specific T-cells before transplantation. In case of CMV-infection or reactiviation, valganciclovir therapy will only be carried out until there is a sufficient number of CMV specific T-cells. In the intervention group, valganciclovir will also be administered, when the levels of CMV-specific T-cells falls below the threshold (that is actually determined in our ongoing study) that makes a CMV-reactivation likely.
Thereby the number of viral infections (especially CMV) should be reduced. By more specific use of antiviral therapy and immunosuppression, nephrotoxic effects of calcineurin inhibitors and antiviral agents should be decreased.
Intervention type
Drug
Phase
Not Applicable
Drug names
Valganciclovir
Primary outcome measure
To determine whether the glomerular filtration rate (GFR) (Cystatin C, Filler) 2 years after transplantation is higher, if antiviral therapy and immunosuppressive therapy are additionally steered, based on the number of virus-specific T-cells.
Secondary outcome measures
1. Reduction of viral infections after solid organ transplantation
2. Optimisation of the individual timing of antiviral therapy
3. Optimisation of the immunosuppressive therapy
4. Reduction of nephrotoxic effects of cyclosporin A (CsA) and antiviral agents by optimised dosing
5. Premature study discontinuations due to adverse events (AEs)
All secondary outcome measures will be assessed continuously until the end of the study.
Overall trial start date
01/10/2009
Overall trial end date
30/06/2010
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Patients who are males or non-pregnant females between the ages of 0 and 16 years
2. Patients after kidney or liver transplantation
3. Patients who receive their first or second transplantation
4. Patients who are single-organ recipients
5. If patients are women of childbearing potential, they must have a negative serum pregnancy test with a sensitivity equal to at least 50 mIU/ml before transplantation
6. If patients are women of childbearing potential, they must use two reliable forms of contraception simultaneously unless abstinence is the chosen method. Effective contraception must be used before transplantation, during therapy, and for 6 weeks following discontinuation of immunosuppressive therapy.
7. Patients' guardians must be capable of understanding the purpose and risks of the study
8. Patients whose guardians are willing to give written informed consent and willing to participate in and comply with the study protocol. Patients above 7 years have to agree with the study in addition to the informed consent of the legally authorised representative.
Participant type
Patient
Age group
Child
Gender
Both
Target number of participants
128
Participant exclusion criteria
1. Patients participating in other studies or participated within the last four weeks
2. Patients who are highly sensitised
3. Patients who have previously undergone two organ transplantations
4. Hypersensitivity to any of the components of the medication used
5. Patients from other centres, who are not followed in the outpatient unit of the Hannover Medical School
6. Patients with a peak or current panel-reactive antibodies (PRA) of greater than 50%
7. Pregnant and/or lactating women and women of childbearing potential who are unwilling or unable to use contraception methods as specified
8. Patients whose guardians do not understand the requirements of the study
9. Patients with known positive human immunodeficiency virus-1 (HIV-1) or hepatitis C virus (HCV) test or the presence of hepatitis B surface antigen (HBsAg)
10. Patients with malignancies or history of malignancy, despite post-transplant lymphoproliferative disease
11. Patients who are not eligible in the opinion of the physician
12. Significant medical history and/or treatments for cardiac, renal, neurological, hepatic, endocrine diseases, or any laboratory abnormality indicative of a significant underlying condition, that may interfere with patients safety, compliance, or study evaluations, according to the investigator's opinion
Recruitment start date
01/10/2009
Recruitment end date
30/06/2010
Locations
Countries of recruitment
Germany
Trial participating centre
Hannover Medical School (MHH)
Hannover
D-30655
Germany
Funders
Funder type
Hospital/treatment centre
Funder name
The trial is jointly funded by the following organisations:
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Novartis (Germany)
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
corporate
Location
Switzerland
Funder name
Medical School of Hannover (MHH) (Germany) - IFB Transplantation
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2014 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/25127887
Publication citations
-
Protocol
Ahlenstiel-Grunow T, Koch A, Großhennig A, Frömke C, Sester M, Sester U, Schröder C, Pape L, A multicenter, randomized, open-labeled study to steer immunosuppressive and antiviral therapy by measurement of virus (CMV, ADV, HSV)-specific T cells in addition to determination of trough levels of immunosuppressants in pediatric kidney allograft recipients (IVIST01-trial): study protocol for a randomized controlled trial., Trials, 2014, 15, 324, doi: 10.1186/1745-6215-15-324.