Transplant Trial Watch

Challenges of calcineurin inhibitor withdrawal following combined pancreas and kidney transplantation: Results of a prospective, randomized clinical trial.

Stock, P. G., et al.

American Journal of Transplantation 2020 [record in progress]

The aim of this study was to assess the long term effects of a calcineurin inhibitor (CNI)-free, corticosteroid-free belatacept (NULOJIX®) based regimen on the graft function of simultaneous pancreas and kidney (SPK) transplant recipients.

Participants were randomized at a 1:1 ratio to either the NULOJIX®-based maintenance immunosuppressive regimen arm or the CNI-based regimen arm

Simultaneous pancreas and kidney transplant recipients.

The primary endpoint was the assessment of mean glomerular filtration rate (GFR) at 52 weeks. The secondary endpoints were additional measures of kidney function and injury, metabolic and cardiovascular parameters, and measures of pancreatic function and injury at 52 weeks post transplant. The anti-donor reactivity and the occurrence and severity of rejection were also measured.

12 months

CET Conclusions
This is a well conducted multicentre study in simultaneous pancreas-kidney transplantation, a field in which RCTs are few and far between. A study-wide suspension of CNI withdrawal was taken during an interim safety review; 8 of 22 enrolled subjects in the investigational arm had pancreas rejection, all but one shortly after or during CNI withdrawal. Blockade of T-cell co-stimulation with belatacept did not enable CNI to be safely withdrawn in SPK. Low dose CNI however, alongside belatacept and mycophenolate, could prevent rejection of both kidney and pancreas, but with a higher risk of opportunistic infection.

Jadad score

Data analysis
Per protocol analysis

Allocation concealment

Trial registration - NCT01790594

Funding source
Non-industry funded