Transplant Trial Watch

Renal function improvement following ANG-3777 treatment in patients at high risk for delayed graft function after kidney transplantation.

Bromberg, J. S., et al

Transplantation 2020 [record in progress].


Aims
The aim of this study was to investigate the efficacy and safety of ANG-3777 in recipients of kidney transplant showing signs of acute kidney injury (AKI).

Interventions
Patients were randomly assigned in a 2:1 ratio to either the ANG-3777 group or the placebo group.

Participants
28 kidney transplant recipients.

Outcomes
The primary efficacy outcome was the time from kidney transplant to the production of ≥1200 cc of urine over a period of 24 hours. The secondary efficacy outcomes included total daily urine output, serum creatinine, serum C-reactive Protein (CRP) and neutrophil gelatinase-associated lipocalin (NGAL), measured 24-hour creatinine clearance, change from baseline urine production, duration of hospitalization, number of dialysis sessions, acute rejection and the incidence of delayed graft function (DGF). The safety outcomes were the incidence of adverse events (AEs), serious AEs (SAEs), treatment

Follow-up
12 months

CET Conclusions
This is a well-written report of a good quality, multicentre RCT, with some quite exciting results. The study was adequately randomised and was double blinded by using saline infusions for the placebo arm. These were administered at the same time points as the study drug in the other side of the trial. ANG-3777, the study drug, is a hepatocycte growth factor mimetic, and was administered to the study arm patients on 3 occasions in the first 3 days after transplantation. The primary outcome was achieving 1.2litres/24 hours urine output, by 28 days post-transplantation. The study drug was associated with a significant improvement in urine output to this extent (approximately 79% versus 44%). Compared to placebo, patients in the study arm also had; lower serum creatinine at multiple time-points; fewer dialysis sessions; shorter hospital stay; significantly less graft failure; and higher eGFR. Further recruitment was halted by the FDA after analysis of the first 28 patients, as a significant efficacy result was seen, and a phase III trial was initiated.

Jadad score
4

Data analysis
Per protocol analysis

Allocation concealment
Yes

Trial registration
N/A

Funding source
Non-industry funded