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Active, Not Recruiting

NCT Number: NCT04901169

Angiotensin II in Liver Transplantation

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Liver Transplant; Complications Acute Kidney Injury Cardiovascular Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Fibrosis Hypotension Kidney Diseases Male Urogenital Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Postoperative Complications Renal Insufficiency Urogenital Diseases Urologic Diseases Vascular Diseases Vasoplegia

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

University of California, San Francisco

San Francisco, California, 94143, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Angiotensin II

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.

Other names: Giapreza (synthetic human angiotensin II)

Saline

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.

Other names: 0.9% normal saline

Primary outcomes

  1. Total dose of norepinephrine (NE), averaged over case duration and total body weight, utilized during liver transplantation (LT) to maintain mean arterial pressure (MAP) greater than or equal to 65 mmHg.

    Time frame: Duration of surgery - defined as the time period starting with skin incision by the surgeon, and ending at the time of skin closure, an average of 8 hours.

    Calculated as the sum of all NE doses (in mcg) administered by either infusion or bolus during LT surgery, divided by the subjects total body weight (TBW, in kg), divided by the duration of surgery (in min). The Primary Outcome will be expressed in mcg/kg/min.

Secondary outcomes

  1. Proportion of patients requiring 3rd and 4th line vasopressor infusions (epinephrine or vasopressin) during LT

    Time frame: Duration of surgery - defined as the time period starting with skin incision by the surgeon, and ending at the time of skin closure, an average of 8 hours.

    The proportion of patients requiring 3rd and 4th line vasopressors (epinephrine or vasopressin, at the anesthesiologists discretion) in addition to NE and Study Drug to be administered by infusion for greater than or equal to 5 min during each of the following phases of LT will be tabulated:

    • Dissection phase - begins at the time of skin incision and ends with clamping of the inferior vena cava (IVC)
    • Anhepatic phase - begins at the time of IVC clamping and ends with unclamping of the portal vein
    • Neohepatic phase - begins at the time of portal vein unclamping and ends at the time of skin closure

  2. Time spent below target MAP (65 mmHg)

    Time frame: Duration of surgery - defined as the time period starting with skin incision by the surgeon, and ending at the time of skin closure, an average of 8 hours.

    Total time in minutes that the patient has a MAP <65 mmHg during LT.

  3. Dose of vasopressin administered during LT, averaged over case duration and TBW.

    Time frame: Duration of surgery - defined as the time period starting with skin incision by the surgeon, and ending at the time of skin closure, an average of 8 hours.

    Calculated as the sum of all vasopressin doses (in units) administered by either infusion or bolus during LT surgery, divided by the subject's TBW (in kg), divided by the duration of surgery (in hr). Expressed in units/kg/hr.

  4. Dose of epinephrine administered during LT, excluding boluses within the 5 min immediately following portal reperfusion, averaged over case duration and TBW.

    Time frame: Duration of surgery - defined as the time period starting with skin incision by the surgeon, and ending at the time of skin closure, an average of 8 hours.

    Calculated as the sum of all epinephrine doses (in mcg) administered by either infusion or bolus during LT surgery, divided by the subject's TBW (in kg), divided by the duration of surgery (in min). Expressed in mcg/kg/min. Boluses of epinephrine given from 0 to 5 min after portal vein reperfusion will be excluded.

  5. Change in direct renin

    Time frame: Time of surgical incision and 2 hours after reperfusion of the portal vein, approximately 4 hours.

    Change in plasma direct renin level from the time of surgical incision to 2 hours after reperfusion of the portal vein

  6. Incidence of severe (stage 2 or 3) acute kidney injury (AKI) within 48 hours after LT.

    Time frame: 48 hours

    The incidence of severe AKI (stage 2 or 3) is defined according to the International Club for Ascites (ICA) 2015 criteria, a revision of the Kidney Disease Improving Global Outcomes (KDIGO) criteria for patients with cirrhosis. Severe AKI is defined as an increase in sCr > 2-fold from baseline, or sCr ≥ 4.0 with an acute increase of ≥ 0.3 mg/dL from baseline, or initiation of RRT. The baseline sCr is defined as the most recent value prior to LT. Limited to the stratum of patients not on RRT immediately prior to surgery.

  7. Change in intraoperative urine output in mL/kg/hr before and after initiation of study drug

    Time frame: Duration of surgery - defined as the time period starting with skin incision by the surgeon, and ending at the time of skin closure, an average of 8 hours.

    Intraoperative urine output will be continuously monitored using an automated meter (Accuryn Monitoring System, Potrero Medical). The change in the rate of urine output will be compared before and after initiation of the study drug.

  8. Major adverse kidney events (MAKE) at 30 days (MAKE-30) after LT

    Time frame: 30 days

    Defined as the composite of death, RRT, or a 25% reduction in estimated glomerular filtration rate (eGFR) by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation at 30 days after LT.

  9. Incidence of early allograft dysfunction (EAD) by Olthoff criteria

    Time frame: 7 days

    Defined by one or more of the following:

    • Total bilirubin ≥ 10 mg/dL on postoperative day (POD) 7
    • International normalized ratio (INR) ≥ 1.6 on POD 7
    • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2000 units/L within the first 7 days after LT

  10. Model for Early Allograft Function (MEAF) score

    Time frame: 3 days

    Calculated from the maximum ALT and INR within the first 3 PODs and the total bilirubin on POD 3. The MEAF score ranges from 0-10 with higher scores indicating worse liver function (i.e., more severe early allograft dysfunction) in the early postoperative period.

  11. Duration of renal replacement therapy (RRT) after LT

    Time frame: Up to 1 year

    Total duration of RRT following LT, limited to the stratum of subjects on RRT immediately prior to surgery.

  12. Duration of ICU stay after LT

    Time frame: Up to 1 year

    Total duration of intensive care unit stay following LT.

  13. Duration of hospital stay after LT

    Time frame: Up to 1 year

    Total duration of hospital stay after LT

  14. Patient and graft survival at 30 days after LT

    Time frame: 30 days

    Defined as patient death or need for re-transplant within 30 days following LT.

  15. Patient and graft survival at 1 year after LT

    Time frame: 1 year

    Defined as patient death or need for re-transplant within 1 year following LT.

Sponsors and collaborators

Lead sponsor

University of California, San Francisco

Other

Collaborators

  • La Jolla Pharmaceutical Company

Registry information

Official study title

Angiotensin II in Liver Transplantation (AngLT-1): A Pilot Randomized Controlled Trial

Acronym: AngLT-1

Important dates

Study start
2022
Primary completion
2026
Study completion
2027
First posted
May 25, 2021
Registry last updated
Mar 20, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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