Angiotensin II in Liver Transplantation (AngLT-1)

University of California San Francisco (UCSF)

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Vasoplegia; Liver Transplant; Complications

Treatments: Drug: Angiotensin II; Drug: Saline

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04901169

20-30948

Details and patient eligibility

About

The purpose of this study is to determine the efficacy and safety of Angiotensin II as a second-line vasopressor (drug that raises the blood pressure) during liver transplantation.

Full description

This is a single center, randomized, double-blind, placebo-controlled trial. Subjects will receive an infusion of either Angiotensin II (AngII) or a saline control (placebo) in addition to usual care with traditional vasopressors (catecholamines and vasopressin) during liver transplantation (LT). AngII is a vasopressor approved by the FDA for the treatment of vasodilatory shock. It targets the renin-angiotensin system (RAS) and has been shown to effectively raise the mean arterial blood pressure (MAP) in patients with septic shock. It also allows for lower doses of traditional vasopressors and may improve microcirculatory flow to the kidneys. The study drug will only be administered if the participants require > 0.05 mcg/kg/min of norepinephrine while undergoing liver transplantation. The study drug will be titrated throughout the case and discontinued at the end of surgery. Randomization will be stratified based on (a) the need for renal replacement therapy preoperatively and (b) the use of normothermic machine perfusion of the liver graft.

Enrollment: 50 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age > or = 18 years
• Liver transplantation from a deceased donor
• Model for End-stage Liver Disease Sodium (MELD-Na) score > or = 25 at the time of transplant (not counting MELD exception points)
• Patient requiring > 0.05 mcg/kg/min of norepinephrine (NE) during LT

Exclusion criteria

• Living-donor liver transplantation (LDLT)
• Split liver transplantation (isolated right or left lobe)
• Donation after cardiac death (DCD) without normothermic machine perfusion (NMP)
• Acute liver failure (ALF)
• Listed for or receiving simultaneous liver-kidney transplantation (SLKT)
• Liver re-transplantation (patient who has previously received a liver transplant)
• Preoperative treatment with angiotensin II receptor blocker or angiotensin converting enzyme inhibitor (within 48 h)
• Portopulmonary hypertension
• Left ventricular systolic dysfunction (defined as ejection fraction < 45%)
• Active bronchospasm at time of LT
• History of thrombotic or embolic disease, inherited hypercoagulable disorder, or therapeutic anticoagulation
• Portal vein thrombosis
• Celiac stenosis
• End-stage renal disease (chronic eGFR < 15 mL/min/1.73 m2 or chronic RRT - not including AKI requiring RRT)
• History of Raynaud's disease
• Known history of allergy to synthetic human angiotensin II
• Subject intubated and/or mechanically ventilated prior to entering OR for LT
• Presence of other condition or abnormality that would compromise the safety of the patient or quality of the data

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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50 participants in 2 patient groups, including a placebo group

Angiotensin II (Giapreza)

Experimental group

Description:

Giapreza (synthetic human angiotensin II), initiated at 5 ng/kg/min and titrated to between 1.25 ng/kg/min and 40 ng/kg/min, administered by continuous intravenous infusion.

Treatment:

Drug: Angiotensin II

Saline

Placebo Comparator group

Description:

Sterile 0.9% saline, initiated and titrated at an equivalent volume infusion rate to the study drug, administered by continuous intravenous infusion.

Treatment:

Drug: Saline