Immunomonitoring by virus-specific T-cells and evaluation as a prognostic marker for virus-induced diseases after solid organ transplantation
| ISRCTN | ISRCTN89806912 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN89806912 |
| Secondary identifying numbers | IVIST01 |
- Submission date
- 29/04/2009
- Registration date
- 17/06/2009
- Last edited
- 18/02/2021
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Surgery
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Not provided at time of registration
Contact information
Dr Lars Pape
Scientific
Scientific
Hannover Medical School (MHH)
Department of Paediatric Nephrology
Carl-Neuberg-Strasse 1
Hannover
D-30655
Germany
Study information
| Study design | Monocentre randomised open-label study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| 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 acronym | IVIST |
| Study objectives | Monitoring of virus-specific T-cells followed by therapeutic intervention can prolong kidney function and reduce viral infections after solid organ transplantation. |
| Ethics approval(s) | Ethics Committee of the Medical School of Hannover, 21/11/2008, ref: 5067 |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | 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 study start date | 01/10/2009 |
| Completion date | 30/06/2010 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Child |
| Upper age limit | 16 Years |
| Sex | Both |
| Target number of participants | 128 |
| Total final enrolment | 64 |
| Key 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. |
| Key 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 |
| Date of first enrolment | 01/10/2009 |
| Date of final enrolment | 30/06/2010 |
Locations
Countries of recruitment
- Germany
Study participating centre
Hannover Medical School (MHH)
Hannover
D-30655
Germany
D-30655
Germany
Sponsor information
Medical School of Hannover (MHH) (Germany)
University/education
University/education
c/o Dr. med. Lars Pape
Department of Pediatric Nephrology
Carl-Neuberg-Strasse 1
Hannover
D-30625
Germany
"ROR" |
https://ror.org/00f2yqf98 |
|---|
Funders
Funder type
Hospital/treatment centre
Novartis
Government organisation / For-profit companies (industry)
Government organisation / For-profit companies (industry)
- Alternative name(s)
- Novartis AG, Novartis International AG
- Location
- Switzerland
Medical School of Hannover (MHH) (Germany) - IFB Transplantation
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 15/08/2014 | Yes | No | |
| Results article | results | 01/02/2021 | 18/02/2021 | Yes | No |
Editorial Notes
18/02/2021: Publication reference and total final enrolment added.
