Transplant Trial Watch

Effect of the proton-pump Inhibitor pantoprazole on MycoPhenolic ACid exposure in kidney and liver transplant recipienTs (IMPACT study): a randomized trial.

Sunderland, A., et al.

Nephrology Dialysis Transplantation 2020; 35(6): 1060-1070.


Aims
The aim of this study was to examine the effect of pantoprazole, a proton-pump inhibitor (PPI), on the pharmacokinetics of mycophenolic acid (MPA) in liver or renal transplant patients maintained on enteric-coated salt form mycophenolate sodium (EC-MPS) or mycophenolate mofetil (MMF).

Interventions
Participants were randomized to either the pantoprazole group or the placebo group, which was followed by a 7-day wash-out period. They were then assigned to the alternative study medication.

Participants
40 kidney transplant patients and 1 liver transplant patient (19 were maintained on MMF, 21 were maintained on EC-MPS and 1 withdrew consent after randomization).

Outcomes
The primary outcome was the pharmacokinetic profile of MPA and MPA-glucuronide when administered together with either pantoprazole or placebo. The secondary outcomes were graft failure, acute rejection (biopsy-proven) and the incidence of adverse events.

Follow-up
2 weeks

CET Conclusions
This is a well conducted study that is clearly described in this report. It is a double-blind, placebo-controlled crossover RCT from 2 centres in Australia. The hypothesis to be tested was that increasing gastric pH with the PPI pantoprazole would reduce the systemic exposure of MPA for patients on MMF, but not enteric coated MMF. The study was adequately powered to detect a significant difference in MPA- AUC- 12hours of more than 25% with and without pantoprazole. The study included 39 kidney transplant recipients and 1 liver transplant recipient. For patients on MMF, the co-administration of pantoprazole reduced the bioavailability of MPA. For patients on enteric –coated MMF, the co-administration of pantoprazole had the opposite effect, increasing the bioavailability of MPA. There were no serious adverse events but the study was not large enough, nor had long enough follow up, to know if the differences in bioavailability would have any definite effects on transplant outcomes.

Jadad score
4

Data analysis
Per protocol analysis

Allocation concealment
Yes

Trial registration
ACTRN12611000316909

Funding source
Non-industry funded