Phase 3 trial Design of the Hepatocyte Growth Factor Mimetic ANG-3777 in Renal Transplant Recipients With Delayed Graft Function.Vincenti, F., et al.
KI Reports 2021; 6(2): 296-303.
The aim of this study is to investigate the role of ANG-3777 treatment in kidney transplant patients showing signs of delayed graft function (DGF).
Participants will be randomised to either the ANG-3777 group or the placebo group.
Adult deceased donor kidney transplant patients (≥18 years).
The primary outcome is the estimated glomerular filtration rate (eGFR). The secondary outcomes include proportion of patients with eGFR >30 at different follow-up time points; proportion of patients with slow graft functon, delayed graft function or primary nonfunction; duration of hospitalisation; duration of dialysis; and adverse events.
The paper describes the design of a phase III trial of a novel intervention to reduce the consequences of DGF following renal transplantation. Patients with delayed function (defined by urine output during the first 24 hours post-transplant) will be randomised to ANG-3777 (a hepatocyte growth factor mimetic) or placebo for 3 days. ANG-3777 has been shown in a phase II study to speed up the return of function following transplantation – this study builds on that to look at the impact on 12-month graft function in a larger cohort. The study is designed to meet FDA regulatory requirements, and as such the design is robust with blinding and selection of an FDA-mandated primary endpoint. Perhaps the only slightly controversial aspect of the design is that rather than recruiting an unselected cohort of consecutive transplants, the recruitment of DCD recipients is capped at 20% of the overall study cohort. Given that incidence of DGF is highest in this population and therefore they are the most likely to benefit, this seems odd. Eligibility criteria requires a urine output of <50ml/hr for 6 consecutive hours in the first 24 hours. This could be criticised as it is easily manipulated by changes in fluid management/diuretic use, but it is difficult to define another early parameter that would better predict the transplant at risk of DGF, unless some kind of clinical risk score from donor/recipient/transplant variables is applied.
ClinicalTrials.gov - NCT02474667