Weinberg Ethan, Rahematpura Suditi, Gonzalez Stevan A, Izzy Manhal J, Simonetto Douglas A, Frederick R Todd, Rubin Raymond A, Ikahihifo-Bender Jade, Harte Maggie, Kim-Lee Grace, Witkiewicz Sherry, Tobin William, Jamil Khurram, Fricker Zachary, Reddy K Rajender
Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Division of Hepatology, Simmons Transplant Institute, Baylor Scott and White All Saints Medical Center, Fort Worth, TX, USA.
Contemp Clin Trials Commun. 2023 Oct 5;36:101211. doi: 10.1016/j.conctc.2023.101211. eCollection 2023 Dec.
Hepatorenal syndrome-acute kidney injury (HRS-AKI) carries significant morbidity and mortality among those with end-stage liver disease. Bolus terlipressin for treatment of HRS-AKI received FDA approval in September 2022. US implementation of terlipressin, however, is hindered by the paucity of local data on the optimal patient population and administration mode, as well as the effect on transplant priority. The INFUSE study is designed to evaluate the use of continuous terlipressin infusion among transplant candidates with advanced liver disease and HRS-AKI.
Fifty prospective patients with HRS-AKI will receive a single bolus of terlipressin 0.5 mg followed by continuous infusions of terlipressin from 2 to 8 mg/day for up to 14 days. The cohort will be enriched with those listed, in evaluation, or eligible for liver transplantation, while those with ACLF grade 3, MELD ≥35, and serum creatinine >5.0 mg/dL will be excluded. Fifty patients who received midodrine plus octreotide or norepinephrine for HRS-AKI will serve as a retrospective comparator cohort.
The INFUSE study aims to assess the safety and efficacy of continuous terlipressin infusion among largely transplant-eligible patients with HRS-AKI, and to provide US-based data on transplant outcomes. This novel study design simultaneously mitigates terlipressin adverse events while providing renal benefits to patients, thus addressing the unmet medical need of those with HRS-AKI who have limited treatment options and are awaiting liver transplantation in the US.
肝肾综合征-急性肾损伤（HRS-AKI）在终末期肝病患者中具有显著的发病率和死亡率。2022年9月，用于治疗HRS-AKI的特利加压素大剂量注射疗法获得了美国食品药品监督管理局（FDA）的批准。然而，美国特利加压素的应用受到了限制，因为缺乏关于最佳患者群体、给药方式以及对移植优先级影响的本地数据。INFUSE研究旨在评估持续输注特利加压素在患有晚期肝病和HRS-AKI的移植候选者中的应用。
50名HRS-AKI的前瞻性患者将接受单次0.5毫克特利加压素大剂量注射，随后以每天2至8毫克的剂量持续输注特利加压素，持续14天。该队列将纳入正在评估或符合肝移植条件的患者，而急性肝衰竭3级、终末期肝病模型（MELD）评分≥35且血清肌酐>5.0毫克/分升的患者将被排除。50名接受米多君加奥曲肽或去甲肾上腺素治疗HRS-AKI的患者将作为回顾性对照队列。
INFUSE研究旨在评估持续输注特利加压素在大多数符合移植条件的HRS-AKI患者中的安全性和有效性，并提供基于美国的移植结果数据。这种新颖的研究设计在减轻特利加压素不良事件的同时，为患者带来肾脏益处，从而满足了美国HRS-AKI患者未被满足的医疗需求，这些患者治疗选择有限且正在等待肝移植。
