Condition category
Date applied
Date assigned
Last edited
Prospectively registered
Overall trial status
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information



Primary contact

Dr Lars Pape


Contact details

Hannover Medical School (MHH)
Department of Paediatric Nephrology
Carl-Neuberg-Strasse 1

Additional identifiers

EudraCT number number

Protocol/serial number


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



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


Secondary study design

Randomised controlled trial

Trial setting


Trial type


Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet


Paediatric kidney transplantation


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



Not Applicable

Drug names


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


Overall trial end date


Reason abandoned (if study stopped)


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


Age group




Target number of participants


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 patient’s safety, compliance, or study evaluations, according to the investigator's opinion

Recruitment start date


Recruitment end date



Countries of recruitment


Trial participating centre

Hannover Medical School (MHH)

Sponsor information


Medical School of Hannover (MHH) (Germany)

Sponsor details

c/o Dr. med. Lars Pape
Department of Pediatric Nephrology
Carl-Neuberg-Strasse 1

Sponsor type




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


Funder name

Novartis (Germany)

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

For-profit companies (industry)



Funder name

Medical School of Hannover (MHH) (Germany) - IFB Transplantation

Alternative name(s)

Funding Body Type

Funding Body Subtype


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:

Publication citations

  1. 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.

Additional files

Editorial Notes