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. 2023 Nov 19;13(11):e078713.
doi: 10.1136/bmjopen-2023-078713.

Angiotensin II in liver transplantation (AngLT-1): protocol of a randomised, double-blind, placebo-controlled trial

Michael P Bokoch  1 , Amy T Tran  2 , Erika L Brinson  2 , Sivan G Marcus  2 , Meghana Reddy  2 , Elizabeth Sun  2 , Garrett R Roll  3 , Manuel Pardo  2 , Scott Fields  4 , Dieter Adelmann  2 , Rishi P Kothari  2   5 , Matthieu Legrand  2
Affiliations

Angiotensin II in liver transplantation (AngLT-1): protocol of a randomised, double-blind, placebo-controlled trial

Michael P Bokoch et al. BMJ Open. .

Abstract

Introduction: Catecholamine vasopressors such as norepinephrine are the standard drugs used to maintain mean arterial pressure during liver transplantation. At high doses, catecholamines may impair organ perfusion. Angiotensin II is a peptide vasoconstrictor that may improve renal perfusion pressure and glomerular filtration rate, a haemodynamic profile that could reduce acute kidney injury. Angiotensin II is approved for vasodilatory shock but has not been rigorously evaluated for treatment of hypotension during liver transplantation. The objective is to assess the efficacy of angiotensin II as a second-line vasopressor infusion during liver transplantation. This trial will establish the efficacy of angiotensin II in decreasing the dose of norepinephrine to maintain adequate blood pressure. Completion of this study will allow design of a follow-up, multicentre trial powered to detect a reduction of organ injury in liver transplantation.

Methods and analysis: This is a double-blind, randomised clinical trial. Eligible subjects are adults with a Model for End-Stage Liver Disease Sodium Score ≥25 undergoing deceased donor liver transplantation. Subjects are randomised 1:1 to receive angiotensin II or saline placebo as the second-line vasopressor infusion. The study drug infusion is initiated on reaching a norepinephrine dose of 0.05 µg kg-1 min-1 and titrated per protocol. The primary outcome is the dose of norepinephrine required to maintain a mean arterial pressure ≥65 mm Hg. Secondary outcomes include vasopressin or epinephrine requirement and duration of hypotension. Safety outcomes include incidence of thromboembolism within 48 hours of the end of surgery and severe hypertension. An intention-to-treat analysis will be performed for all randomised subjects receiving the study drug. The total dose of norepinephrine will be compared between the two arms by a one-tailed Mann-Whitney U test.

Ethics and dissemination: The trial protocol was approved by the local Institutional Review Board (#20-30948). Results will be posted on ClinicalTrials.gov and published in a peer-reviewed journal.

Trial registration number: ClinicalTrials.govNCT04901169.

Keywords: Angiotensin II; Blood Pressure; End Stage Liver Disease; Liver Cirrhosis; Liver Transplantation; Vasoconstrictor agents.

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Conflict of interest statement

Competing interests: MB discloses that support was provided by La Jolla Pharmaceutical Company (now Innoviva, Waltham, MA, USA) for this trial as part of an investigator-initiated research proposal. This support consisted of study drug (AngII) at no cost for trial patients only, and $14 231 USD (direct plus indirect costs) to support an assistant research coordinator. La Jolla Pharmaceutical Company reviewed the protocol before trial initiation but suggested no changes. The authors have sole responsibility (independent of La Jolla Pharmaceutical/Innoviva) for conduct of the trial, analysis and interpretation of data, assignment of adverse events and dissemination of results. ML has received consulting fees from La Jolla Pharmaceutical Company, Alexion Pharmaceuticals and SphingoTec GmbH. All other authors have no competing interests to disclose.

Figures

Figure 1
Figure 1
Study drug initiation and titration protocol. NE, norepinephrine; MAP, mean arterial pressure; NE, norepinephrine; AngII, angiotensin II; SBP, systolic blood pressure; DBP, diastolic blood pressure.
Figure 2
Figure 2
Study schedule of enrolment, interventions and assessments. AngII, angiotensin II; NE, norepinephrine.
See this image and copyright information in PMC

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References

    1. Shaefi S, Mittel A, Klick J, et al. . Vasoplegia after cardiovascular procedures-pathophysiology and targeted therapy. J Cardiothorac Vasc Anesth 2018;32:1013–22. 10.1053/j.jvca.2017.10.032 - DOI - PubMed
    1. Chow JH, Abuelkasem E, Sankova S, et al. . Reversal of vasodilatory shock. Anesth Analg 2020;30:15–30. 10.1213/ANE.0000000000004343 - DOI - PubMed
    1. Boettcher BT, Woehlck HJ, Makker H, et al. . Hydroxocobalamin for treatment of catecholamine-resistant vasoplegia during liver transplantation: a single-center series of 20 cases. Int J Surg Case Rep 2022;98:107488. 10.1016/j.ijscr.2022.107488 - DOI - PMC - PubMed
    1. Adelmann D, Kronish K, Ramsay MA. Anesthesia for liver transplantation. Anesthesiol Clin 2017;35:491–508. 10.1016/j.anclin.2017.04.006 - DOI - PubMed
    1. Bezinover D, Mukhtar A, Wagener G, et al. . Hemodynamic instability during liver transplantation in patients with end-stage liver disease: a consensus document from ILTS, LICAGE, and SATA. Transplantation 2021;105:2184–200. 10.1097/TP.0000000000003642 - DOI - PubMed

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