Angiotensin II in Liver Transplantation

NCT ID: NCT04901169

Last Updated: 2025-05-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2/PHASE3

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-06-28

Study Completion Date

2026-09-01

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Liver Transplant; Complications Vasoplegia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Randomized, double-blind, placebo-controlled.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Identically-labeled infusion bags of either angiotensin II or saline placebo will be prepared by a research pharmacist.

Study Groups

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Angiotensin II (Giapreza)

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.

Group Type EXPERIMENTAL

Angiotensin II

Intervention Type DRUG

Infusion of Angiotensin II initiated if participants require norepinephrine at a rate of \> 0.05 mcg/kg/min. The infusion will be titrated no more frequently than every 10 minutes during liver transplantation as a second line vasopressor and discontinued prior to leaving the operating room when the surgery is complete.

Saline

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

Group Type PLACEBO_COMPARATOR

Saline

Intervention Type DRUG

Infusion of 0.9% saline initiated if participants require norepinephrine at a rate of \> 0.05 mcg/kg/min. The infusion will be titrated no more frequently than every 10 minutes during liver transplantation as a second line vasopressor and discontinued prior to leaving the operating room when the surgery is complete.

Interventions

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Angiotensin II

Infusion of Angiotensin II initiated if participants require norepinephrine at a rate of \> 0.05 mcg/kg/min. The infusion will be titrated no more frequently than every 10 minutes during liver transplantation as a second line vasopressor and discontinued prior to leaving the operating room when the surgery is complete.

Intervention Type DRUG

Saline

Infusion of 0.9% saline initiated if participants require norepinephrine at a rate of \> 0.05 mcg/kg/min. The infusion will be titrated no more frequently than every 10 minutes during liver transplantation as a second line vasopressor and discontinued prior to leaving the operating room when the surgery is complete.

Intervention Type DRUG

Other Intervention Names

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Giapreza (synthetic human angiotensin II) 0.9% normal saline

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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La Jolla Pharmaceutical Company

INDUSTRY

Sponsor Role collaborator

University of California, San Francisco

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Michael P Bokoch, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Department of Anesthesia and Perioperative Care, University of California, San Francisco

Locations

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University of California, San Francisco

San Francisco, California, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Michael P Bokoch, M.D., Ph.D.

Role: CONTACT

(415) 476-8389

Facility Contacts

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Michael P Bokoch, MD, PhD

Role: primary

415-476-8389

Dieter Adelmann, MD, PhD

Role: backup

References

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Khanna A, English SW, Wang XS, Ham K, Tumlin J, Szerlip H, Busse LW, Altaweel L, Albertson TE, Mackey C, McCurdy MT, Boldt DW, Chock S, Young PJ, Krell K, Wunderink RG, Ostermann M, Murugan R, Gong MN, Panwar R, Hastbacka J, Favory R, Venkatesh B, Thompson BT, Bellomo R, Jensen J, Kroll S, Chawla LS, Tidmarsh GF, Deane AM; ATHOS-3 Investigators. Angiotensin II for the Treatment of Vasodilatory Shock. N Engl J Med. 2017 Aug 3;377(5):419-430. doi: 10.1056/NEJMoa1704154. Epub 2017 May 21.

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Reference Type DERIVED
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Other Identifiers

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20-30948

Identifier Type: -

Identifier Source: org_study_id

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