Transplant Trial Watch

Efficacy and Safety of a Quadruple Regimen Compared with Triple Regimens in Patients with Mycophenolic Acid-Related Gastrointestinal Complications After Renal Transplantation: A Short-Term Single-Center Study.

Peng, Z., et al.

Annals of Transplantation 2020; 25: e919875.

The primary aim of this study was to investigate whether a quadruple regimen containing standard-dose tacrolimus, corticosteroids, low-dose EC-MPS (enteric-coated mycophenolate sodium) and low-dose MZR (mizoribine) had better safety and efficacy outcomes compared to a triple regimen consisting of corticosteroids and standard-dose tacrolimus with either standard-dose MZR or low-dose EC-MPS in treating renal transplant recipients with MPA (mycophenolic acid) related gastrointestinal complications.

Participants were randomized to one of three groups: the standard-dose MZR group, the low-dose EC-MPS group, or the low-dose EC-MPS plus low-dose MZR group

112 renal transplant recipients with MPA-related gastrointestinal complications.

The main outcomes of interest were changes in the severity of gastrointestinal complications using the Gastrointestinal Symptom Rating Scale (GSRS), renal function (estimated glomerular filtration rate and serum creatinine), graft rejection, patient survival, presence of human leukocyte antigen (HLA) antibodies, and the incidence of adverse events.

1 year

CET Conclusions
This is a single centre randomised controlled trial of immune suppression regimens in the treatment of GI symptoms following renal transplantation. Unfortunately, the method of randomisation is not described in the paper, nor is there any blinding of patients or assessors. This is particularly important as the primary outcome was a self-recorded Gastrointestinal Symptom Rating Score (GSRS). 115 recipients of living donor transplants with GI symptoms were randomised to 1 of three groups and then had their immune suppressions regimens changed. There is no flow chart to demonstrate if there were any dropouts, withdrawals and how complete was the final data. All treatment arms had documented improvements at 3 months in the following symptoms: diarrhoea, abdominal pain, indigestion and reflux. There was no significant improvement in constipation. When comparing between study arms, there was a greater mean reduction in symptom scores for diarrhoea, abdominal pain and indigestion in the treatment arm receiving standard-dose mizoribine than the other two arms. However, the study was powered for the total GSRS symptom score, and this is not presented as a comparative statistic between the study arms in the paper. The low-dose EC-MPS + low-dose mizoribine group had significantly lower rates of acute graft rejection (8.3%) compared to low-dose EC-MPS (18.9%) and standard-dose mizoribine (20.5%). In conclusion, all three treatment arms experienced an improvement in mean GSRS scores after 3 months. There was no significant difference in the change in GSRS total score comparing the three different treatment groups. Whilst there may be some significant improvements in some GI symptoms with mizoribine, its use without MPS may be associated with greater risk of acute rejection.

Jadad score

Data analysis
Per protocol analysis

Allocation concealment

Trial registration

Funding source
Non-industry funded