INFUSE: Rationale and design of a multi-center, open label, collaborative study to treat HRS-AKI with continuous terlipressin infusion.
Ascites
Decompensated cirrhosis
Hepatorenal syndrome
Liver transplant
Portal hypertension
Journal
Contemporary clinical trials communications
ISSN: 2451-8654
Titre abrégé: Contemp Clin Trials Commun
Pays: Netherlands
ID NLM: 101671157
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
17
07
2023
revised:
25
08
2023
accepted:
01
10
2023
medline:
13
11
2023
pubmed:
13
11
2023
entrez:
13
11
2023
Statut:
epublish
Résumé
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.
Sections du résumé
Background
UNASSIGNED
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.
Methods
UNASSIGNED
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.
Conclusion
UNASSIGNED
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.
Identifiants
pubmed: 37953795
doi: 10.1016/j.conctc.2023.101211
pii: S2451-8654(23)00157-6
pmc: PMC10632660
doi:
Types de publication
Journal Article
Langues
eng
Pagination
101211Informations de copyright
© 2023 The Authors.
Déclaration de conflit d'intérêts
The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ethan Weinberg.•Mallinckodt Pharmaceuticals: study funding, DSMB/Advisory board participation•BioVie: consulting•PharmaIN: consulting•Institute for Medical and Nursing Education: lectures/presentations Stevan A. Gonzalez.•Mallinckrodt Pharmaceuticals: advisory board, consulting, Speakers bureau•Salix Pharmaceuticals: consulting, Speakers bureau•AbbVie Pharmaceuticals: Speakers bureau R. Todd Frederick.•Mallinckrodt Pharmaceuticals: consultant Raymond A. Rubin.•Mallinckrodt Pharmaceuticals: clinical trial funding, Speakers bureau William Tobin.•Services contract with UPenn to monitor study data Khurram Jamil.•Mallinckrodt Pharmaceuticals: employee, patents, stock Zachary Fricker.•Mallinckrodt Pharmaceuticals: payments to institution and travel reimbursements K. Rajender Reddy.•Grants/contracts: BMS, Intercept, Mallinckrodt, BioVie, Sequana, Grifols, Exact Sciences, HCC-TARGET, NASH-TARGET, Merck•Royalties/licenses: UpToDate•Consulting: Spark Therapeutics, Novo Nordisk, Mallinckrodt, Genfit, BioVie•DSMB/Advisory Board participation: Novartix, Astra Zeneca•Associate Editor Gastroenterology No disclosures:•Suditi Rahematpura, Manhal J. Izzy, Douglass A. Simonetto, Jade Ikahihifo-Bender, Maggie Harte, Grace Kim-Lee, Sherry Witkiewicz
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