PREventing Delayed Graft Function by Driving Immunosuppressive InduCtion Treatment (PREDICT-DGF): study protocol for a randomized controlled trial

Abstract

BackgroundIn kidney transplantation, the use of Anti-Thymocyte Globulins (ATG) as induction therapy has been described as a possible treatment for reducing the prevalence of Delayed Graft Function (DGF). ATG possesses pharmaceutical proprieties that could help control the lesions caused by ischemia reperfusion injury. However, other studies have questioned this potential protective effect. We hypothesized that the benefits related to ATG for reducing DGF prevalence may be higher and more consistently recognized if only patients with high DGF risk are considered. We recently proposed a scoring system entitled DGFS (Delayed Graft Function Score) for such stratification of kidney transplant recipients according to their risk of DGF. Using the DGFS calculation, we aim to determine whether a short course of ATG can decrease the incidence of DGF in comparison with Basiliximab in kidney transplant recipients with low immunological risk but high DGF risk.MethodsWe conduct a phase IV, open label, randomized, multicentric and prospective study, to compare ATG in parallel with a control group treated by Basiliximab. The 1:1 randomized allocation of patients between groups is stratified on the clinical center, and on the hypothermic machine-perfusion device. We aimed to include a total of 384 patients to achieve a statistical power at 0.80. The study was initiated at the Nantes University hospital in July 2014, with data collection continuing until April 2018, and publication of the results proposed for 2019.DiscussionThe main expected benefits of this study are i) the reduction of unjustified ATG over-prescriptions associated with serious adverse events, ii) the reduction of chance losses related to ATG under-prescription, iii) the decrease in the incidence of DGF which was described as a risk factor of graft failure and patient death, and iv) the reduction in hospitalization duration and number of post transplantation dialysis sessions, both being associated with reduced medical costs. In conclusion, the current study is innovative by proposing a more efficient and personalized induction therapy.Trial registrationThe study was registered in the Clinical Trials Registry (#NCT02056938, February 5, 2014), and in the European Clinical Trials Database (EudraCT #2014-000332-42, January 30, 2014).

Induction Therapy in Half-Haplotype Low Risk Kidney Transplant Patients: Impact on Acute Rejection, Graft Survival, Infection and Surgical Complications at 3 Years

“…In our study, we found that the hospital stay duration and the incidence of DGF were not different between the 2 groups with no impact of DGF on AR rate and GS as well. Our results are in concordance with those of Chapal et al [21] who have questioned the benefit of using ATG in low immunological risk patients. They evaluated its risk/benefit ratio and the consequences of a possible reduction in DGF incidence, against side effects related to such depleting induction therapy.…”

“…Induction therapy using lymphocyte-depleting polyclonal antibodies or lymphocyte non-depleting monoclonal antibodies that inhibit the T-cell response is widely used in KT. It aims to avoid AR in KTRs, to provide an immunologic cover for patients suffering from DGF [21] and to improve both short and long-term outcomes [12]. However, Antibody induction is not without risk.…”

Prediction, prevention, and management of delayed graft function: where are we now?

“…). The ongoing randomized PREDICT‐DGF study is comparing rATG vs basiliximab in a large population of kidney transplant patients at low immunological risk but at high risk for DGF to determine whether DGF rates are lowered under rATG induction …”

“…In contrast, delayed CNI with IL‐2RA induction does not generally appear to lower risk for DGF . The ongoing randomized PREDICT‐DGF study is comparing induction with rATG vs basiliximab, both with delayed CNI initiation as per local practice, in patients at low immunological risk but at high risk for DGF …”

Risk factors for delayed graft function in deceased donor kidney transplantation; a potential preventive role for intraoperative thymoglobulin

“…Rabbit antithymocyte globulin (rATG; thymoglobulin) is frequently used as an induction therapy agent in deceased donor KT especially in recipients with increased immunologic risk factors in order to reduce the risk of graft rejection and DGF (7)(8)(9). It is believed that thymoglobulin has several pharmacologic properties, some of which can help to control the inflammation associated with ischemia reperfusion injury and thus reduce the risk of pathogenesis of DGF (10).…”