Statistical analysis plan for TTVguideIT-a multicentre, patient- and assessor-blinded, non-inferiority, randomised and controlled phase II trial to compare standard and Torque Teno virus-guided immunosuppression in kidney transplant recipients in the first year after transplantation.

BACKGROUND: Non-interventional studies indicate an association between Torque Teno Virus (TTV) load in peripheral blood and immunosuppression related outcomes in kidney transplant recipients. This makes it a promising biomarker for guiding immunosuppression after kidney transplantation. The primary objective of the current trial is to demonstrate the safety, tolerability and preliminary efficacy of TTV-guided immunosuppression.

METHODS: For this purpose, a randomised, controlled, interventional, two-arm, non-inferiority, patient- and assessor-blinded, international multicentre investigator-driven phase II trial was designed. A total of 260 stable, low-immunological-risk adult recipients of a kidney graft with Tacrolimus-based immunosuppression and TTV infection after month 3 post-transplant are recruited in 13 academic centres in six European countries. Subjects are randomised in a 1:1 ratio stratified by centre (allocation concealment) to receive Tacrolimus either guided by TTV load or according to the local centre standard for 9 months. The primary composite endpoint includes the occurrence of infections, biopsy-proven allograft rejection, graft loss or death. Secondary outcomes include month 12 protocol biopsies, development of de novo donor-specific antibodies, health-related quality of life and drug adherence.

DISCUSSION: Detailed descriptions of the study design, planned statistical analysis and reporting of the results for the TTVguideIT trial are provided. This statistical analysis plan was submitted to the journal before the end of the trial and prior to data lock.