Multicentre, multi-arm, double-blind randomised placebo-controlled dose-finding trial investigating the safety and Efficacy of MirococePt (APT070) In Reducing delayed graft function In the Kidney ALlograft (EMPIRIKAL-2): study protocol for a randomised controlled trial

作者：Theodoros Kassimatis, Alima Rahman, Fayyad Jaradat, Abdel Douiri, Marc Delord, Roseanna Greenlaw, J. Joyce, Jonathon Olsburgh, Muhammad Khurram, Abbas Ghazanfar, Simon Knight, Peter J. Friend, Sapna Shah, Hannah Killbride, Richard A. Smith, Steven H. Sacks · 发表于：BMJ Open · 年份：2025 · DOI：10.1136/bmjopen-2024-097029 · 被引用次数：4 · 研究领域：Complement system in diseases、Renal Transplantation Outcomes and Treatments、Organ Donation and Transplantation

BACKGROUND: Up to 50% of kidney transplant patients are diagnosed with delayed graft function (DGF) following transplantation-the majority being linked to ischaemia reperfusion injury (IRI). DGF is traditionally defined as the requirement for dialysis during the first week after transplantation and is associated with inferior graft and patient outcomes. Local synthesis of complement components, largely by the renal tubule, plays a critical role in IRI. We have developed Mirococept, a membrane-targeted complement inhibitor, that can be administered to the donor kidney ex vivo prior to transplantation. After administration, Mirococept is retained in the donor organ, thereby minimising the risk of systemic side effects. We previously launched the EMPIRIKAL study aiming to evaluate the efficacy of Mirococept in reducing DGF in deceased-donor kidney transplantation (KT). The funding body recommended termination of the study to allow a dose-saturating study before the next stage of clinical evaluation. This was carried out in a porcine kidney model and led to a revised dosing regimen for EMPIRIKAL-2 (60-180 mg compared with 5-25 mg in the initial trial). The EMPIRIKAL-2 trial (REC 24/NE/0071) aims to identify the most safe and efficacious dose of Mirococept to reduce DGF rate in deceased-donor KT. METHODS AND ANALYSIS: EMPIRIKAL-2 is a Phase IIa multicentre double-blind randomised controlled trial (RCT) with an initial safety run. Participants will be recruited from renal departmen...