Liver Transplant; ComplicationsPhase 2/3AngLT-1NCT04901169
Angiotensin II in Liver Transplantation
A Phase 2/3 study testing Angiotensin II and Saline in people with Liver Transplant; Complications and Vasoplegia, run by University of California, San Francisco at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Transplant; Complications, Vasoplegia
- What is being tested?
- Angiotensin II and Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Jun 2022to 18 Mar 2027
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 18Show fewer
- 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 locations and contacts
1 site in 1 country.
United States1 site
University of California, San Francisco
San Francisco, California, 94143
About this study
Official title: Angiotensin II in Liver Transplantation (AngLT-1): A Pilot Randomized Controlled Trial
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.
Read the detailed 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.
- Conditions
- Liver Transplant; Complications, Vasoplegia
- Being tested
- Angiotensin II, Saline
- Keywords
- Vasoplegia, Angiotensin II, Cirrhosis, Liver Transplant, Liver Transplantation, Hypotension, Acute Kidney Injury
- Medical subject headings
- Vasoplegia, Fibrosis, Hypotension, Acute Kidney Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Angiotensin IIDrug
Also called Giapreza (synthetic human 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.
SalineDrug
Also called 0.9% normal 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.
| Study group | Role | What they receive |
|---|---|---|
| Angiotensin II (Giapreza) | Experimental | 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. Receives: Drug: Angiotensin II |
| Saline | Placebo comparator | Sterile 0.9% saline, initiated and titrated at an equivalent volume infusion rate to the study drug, administered by continuous intravenous infusion. Receives: Drug: Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
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.
Measured: 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.
Secondary outcomes (15)
Proportion of patients requiring 3rd and 4th line vasopressor infusions (epinephrine or vasopressin) during LT
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
Measured: 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.
Time spent below target MAP (65 mmHg)
Total time in minutes that the patient has a MAP <65 mmHg during LT.
Measured: 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.
Dose of vasopressin administered during LT, averaged over case duration and TBW.
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.
Measured: 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.
Dose of epinephrine administered during LT, excluding boluses within the 5 min immediately following portal reperfusion, averaged over case duration and TBW.
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.
Measured: 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.
Change in direct renin
Change in plasma direct renin level from the time of surgical incision to 2 hours after reperfusion of the portal vein
Measured: Time of surgical incision and 2 hours after reperfusion of the portal vein, approximately 4 hours.
Incidence of severe (stage 2 or 3) acute kidney injury (AKI) within 48 hours after LT.
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.
Measured: 48 hours
Change in intraoperative urine output in mL/kg/hr before and after initiation of study drug
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.
Measured: 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.
Major adverse kidney events (MAKE) at 30 days (MAKE-30) after LT
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.
Measured: 30 days
Incidence of early allograft dysfunction (EAD) by Olthoff criteria
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
Measured: 7 days
Model for Early Allograft Function (MEAF) score
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.
Measured: 3 days
Duration of renal replacement therapy (RRT) after LT
Total duration of RRT following LT, limited to the stratum of subjects on RRT immediately prior to surgery.
Measured: Up to 1 year
Duration of ICU stay after LT
Total duration of intensive care unit stay following LT.
Measured: Up to 1 year
Duration of hospital stay after LT
Total duration of hospital stay after LT
Measured: Up to 1 year
Patient and graft survival at 30 days after LT
Defined as patient death or need for re-transplant within 30 days following LT.
Measured: 30 days
Patient and graft survival at 1 year after LT
Defined as patient death or need for re-transplant within 1 year following LT.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2021
- Study start28 Jun 2022
- Primary completion18 Mar 2026
- Study completion18 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (16)Papers the sponsor has linked to this study.
- Other trials for Liver Transplant; ComplicationsStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, double-blind, placebo-controlled.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- La Jolla Pharmaceutical Company
- Responsible party
- Sponsor
- Investigators
- Michael P Bokoch, M.D., Ph.D., Principal investigator, Department of Anesthesia and Perioperative Care, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04901169
- Sponsor's protocol ID
- 20-30948
- Acronym
- AngLT-1
- Status last verified
- Mar 2026
- First submitted
- 20 May 2021
- Last updated
- 20 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 28528561Tumlin JA, Murugan R, Deane AM, Ostermann M, Busse LW, Ham KR, Kashani K, Szerlip HM, Prowle JR, Bihorac A, Finkel KW, Zarbock A, Forni LG, Lynch SJ, Jensen J, Kroll S, Chawla LS, Tidmarsh GF, Bellomo R; Angiotensin II for the Treatment of High-Output Shock 3 (ATHOS-3) Investigators. Outcomes in Patients with Vasodilatory Shock and Renal Replacement Therapy Treated with Intravenous Angiotensin II. Crit Care Med. 2018 Jun;46(6):949-957. doi: 10.1097/CCM.0000000000003092.
PubMed 29509568Shim KY, Eom YW, Kim MY, Kang SH, Baik SK. Role of the renin-angiotensin system in hepatic fibrosis and portal hypertension. Korean J Intern Med. 2018 May;33(3):453-461. doi: 10.3904/kjim.2017.317. Epub 2018 Feb 21.
PubMed 29462546Casey S, Schierwagen R, Mak KY, Klein S, Uschner F, Jansen C, Praktiknjo M, Meyer C, Thomas D, Herath C, Jones R, Trebicka J, Angus P. Activation of the Alternate Renin-Angiotensin System Correlates with the Clinical Status in Human Cirrhosis and Corrects Post Liver Transplantation. J Clin Med. 2019 Mar 27;8(4):419. doi: 10.3390/jcm8040419.
PubMed 30934723Coleman PJ, Nissen AP, Kim DE, Ainsworth CR, McCurdy MT, Mazzeffi MA, Chow JH. Angiotensin II in Decompensated Cirrhosis Complicated by Septic Shock. Semin Cardiothorac Vasc Anesth. 2020 Sep;24(3):266-272. doi: 10.1177/1089253219877876. Epub 2019 Sep 20.
PubMed 31540560Busse LW, Wang XS, Chalikonda DM, Finkel KW, Khanna AK, Szerlip HM, Yoo D, Dana SL, Chawla LS. Clinical Experience With IV Angiotensin II Administration: A Systematic Review of Safety. Crit Care Med. 2017 Aug;45(8):1285-1294. doi: 10.1097/CCM.0000000000002441.
PubMed 28489648Angeli P, Gines P, Wong F, Bernardi M, Boyer TD, Gerbes A, Moreau R, Jalan R, Sarin SK, Piano S, Moore K, Lee SS, Durand F, Salerno F, Caraceni P, Kim WR, Arroyo V, Garcia-Tsao G; International Club of Ascites. Diagnosis and management of acute kidney injury in patients with cirrhosis: revised consensus recommendations of the International Club of Ascites. Gut. 2015 Apr;64(4):531-7. doi: 10.1136/gutjnl-2014-308874. Epub 2015 Jan 28. No abstract available.
PubMed 25631669Olthoff KM, Kulik L, Samstein B, Kaminski M, Abecassis M, Emond J, Shaked A, Christie JD. Validation of a current definition of early allograft dysfunction in liver transplant recipients and analysis of risk factors. Liver Transpl. 2010 Aug;16(8):943-9. doi: 10.1002/lt.22091.
PubMed 20677285Pareja E, Cortes M, Hervas D, Mir J, Valdivieso A, Castell JV, Lahoz A. A score model for the continuous grading of early allograft dysfunction severity. Liver Transpl. 2015 Jan;21(1):38-46. doi: 10.1002/lt.23990. Epub 2014 Nov 24.
PubMed 25204890Kellum JA, Zarbock A, Nadim MK. What endpoints should be used for clinical studies in acute kidney injury? Intensive Care Med. 2017 Jun;43(6):901-903. doi: 10.1007/s00134-017-4732-1. Epub 2017 Mar 2. No abstract available.
PubMed 28255614Bellomo R, Forni LG, Busse LW, McCurdy MT, Ham KR, Boldt DW, Hastbacka J, Khanna AK, Albertson TE, Tumlin J, Storey K, Handisides D, Tidmarsh GF, Chawla LS, Ostermann M. Renin and Survival in Patients Given Angiotensin II for Catecholamine-Resistant Vasodilatory Shock. A Clinical Trial. Am J Respir Crit Care Med. 2020 Nov 1;202(9):1253-1261. doi: 10.1164/rccm.201911-2172OC.
PubMed 32609011Depret F, Amzallag J, Pollina A, Fayolle-Pivot L, Coutrot M, Chaussard M, Santos K, Hartmann O, Jully M, Fratani A, Oueslati H, Cupaciu A, Benyamina M, Guillemet L, Deniau B, Mebazaa A, Gayat E, Farny B, Textoris J, Legrand M; PRONOBURN group. Circulating dipeptidyl peptidase-3 at admission is associated with circulatory failure, acute kidney injury and death in severely ill burn patients. Crit Care. 2020 Apr 22;24(1):168. doi: 10.1186/s13054-020-02888-5.
PubMed 32321571Hollinger A, Wittebole X, Francois B, Pickkers P, Antonelli M, Gayat E, Chousterman BG, Lascarrou JB, Dugernier T, Di Somma S, Struck J, Bergmann A, Beishuizen A, Constantin JM, Damoisel C, Deye N, Gaudry S, Huberlant V, Marx G, Mercier E, Oueslati H, Hartmann O, Sonneville R, Laterre PF, Mebazaa A, Legrand M. Proenkephalin A 119-159 (Penkid) Is an Early Biomarker of Septic Acute Kidney Injury: The Kidney in Sepsis and Septic Shock (Kid-SSS) Study. Kidney Int Rep. 2018 Aug 22;3(6):1424-1433. doi: 10.1016/j.ekir.2018.08.006. eCollection 2018 Nov.
PubMed 30450469Albert C, Zapf A, Haase M, Rover C, Pickering JW, Albert A, Bellomo R, Breidthardt T, Camou F, Chen Z, Chocron S, Cruz D, de Geus HRH, Devarajan P, Di Somma S, Doi K, Endre ZH, Garcia-Alvarez M, Hjortrup PB, Hur M, Karaolanis G, Kavalci C, Kim H, Lentini P, Liebetrau C, Lipcsey M, Martensson J, Muller C, Nanas S, Nickolas TL, Pipili C, Ronco C, Rosa-Diez GJ, Ralib A, Soto K, Braun-Dullaeus RC, Heinz J, Haase-Fielitz A. Neutrophil Gelatinase-Associated Lipocalin Measured on Clinical Laboratory Platforms for the Prediction of Acute Kidney Injury and the Associated Need for Dialysis Therapy: A Systematic Review and Meta-analysis. Am J Kidney Dis. 2020 Dec;76(6):826-841.e1. doi: 10.1053/j.ajkd.2020.05.015. Epub 2020 Jul 15.
PubMed 32679151Nalesso F, Cattarin L, Gobbi L, Fragasso A, Garzotto F, Calo LA. Evaluating Nephrocheck(R) as a Predictive Tool for Acute Kidney Injury. Int J Nephrol Renovasc Dis. 2020 Apr 24;13:85-96. doi: 10.2147/IJNRD.S198222. eCollection 2020.
PubMed 32425580
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Angiotensin II in Liver Transplantation (AngLT-1): A Pilot Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT04901169
- Acronym / sponsor ID
- AngLT-1 / 20-30948
- Conditions
- Liver Transplant; Complications, Vasoplegia
- Keywords
- Vasoplegia, Angiotensin II, Cirrhosis, Liver Transplant, Liver Transplantation, Hypotension, Acute Kidney Injury
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- La Jolla Pharmaceutical Company
- Study start
- 28 Jun 2022 (actual)
- Primary completion
- 18 Mar 2026 (actual)
- Study completion
- 18 Mar 2027 (estimated)
- First posted
- 25 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized, double-blind, placebo-controlled.
| Arm | Type | Receives |
|---|---|---|
| Angiotensin II (Giapreza) | Experimental | Drug: Angiotensin IIGiapreza (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. |
| Saline | Placebo comparator | Drug: SalineSterile 0.9% saline, initiated and titrated at an equivalent volume infusion rate to the study drug, administered by continuous intravenous infusion. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (18 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Angiotensin IIAlso: Giapreza (synthetic human 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. | Drug | Angiotensin II (Giapreza) |
| SalineAlso: 0.9% normal salineInfusion 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. | Drug | Saline |
Primary outcome
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.
15 secondary outcomes
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.
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.
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.
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.
Change in direct renin
Time frame: Time of surgical incision and 2 hours after reperfusion of the portal vein, approximately 4 hours.
Incidence of severe (stage 2 or 3) acute kidney injury (AKI) within 48 hours after LT.
Time frame: 48 hours
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.
Major adverse kidney events (MAKE) at 30 days (MAKE-30) after LT
Time frame: 30 days
Incidence of early allograft dysfunction (EAD) by Olthoff criteria
Time frame: 7 days
Model for Early Allograft Function (MEAF) score
Time frame: 3 days
Duration of renal replacement therapy (RRT) after LT
Time frame: Up to 1 year
Duration of ICU stay after LT
Time frame: Up to 1 year
Duration of hospital stay after LT
Time frame: Up to 1 year
Patient and graft survival at 30 days after LT
Time frame: 30 days
Patient and graft survival at 1 year after LT
Time frame: 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2026.
- Background: PubMed 28528561Khanna 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.
- Background: PubMed 29509568Tumlin JA, Murugan R, Deane AM, Ostermann M, Busse LW, Ham KR, Kashani K, Szerlip HM, Prowle JR, Bihorac A, Finkel KW, Zarbock A, Forni LG, Lynch SJ, Jensen J, Kroll S, Chawla LS, Tidmarsh GF, Bellomo R; Angiotensin II for the Treatment of High-Output Shock 3 (ATHOS-3) Investigators. Outcomes in Patients with Vasodilatory Shock and Renal Replacement Therapy Treated with Intravenous Angiotensin II. Crit Care Med. 2018 Jun;46(6):949-957. doi: 10.1097/CCM.0000000000003092.
- Background: PubMed 29462546Shim KY, Eom YW, Kim MY, Kang SH, Baik SK. Role of the renin-angiotensin system in hepatic fibrosis and portal hypertension. Korean J Intern Med. 2018 May;33(3):453-461. doi: 10.3904/kjim.2017.317. Epub 2018 Feb 21.
- Background: PubMed 30934723Casey S, Schierwagen R, Mak KY, Klein S, Uschner F, Jansen C, Praktiknjo M, Meyer C, Thomas D, Herath C, Jones R, Trebicka J, Angus P. Activation of the Alternate Renin-Angiotensin System Correlates with the Clinical Status in Human Cirrhosis and Corrects Post Liver Transplantation. J Clin Med. 2019 Mar 27;8(4):419. doi: 10.3390/jcm8040419.
- Background: PubMed 31540560Coleman PJ, Nissen AP, Kim DE, Ainsworth CR, McCurdy MT, Mazzeffi MA, Chow JH. Angiotensin II in Decompensated Cirrhosis Complicated by Septic Shock. Semin Cardiothorac Vasc Anesth. 2020 Sep;24(3):266-272. doi: 10.1177/1089253219877876. Epub 2019 Sep 20.
- Background: PubMed 28489648Busse LW, Wang XS, Chalikonda DM, Finkel KW, Khanna AK, Szerlip HM, Yoo D, Dana SL, Chawla LS. Clinical Experience With IV Angiotensin II Administration: A Systematic Review of Safety. Crit Care Med. 2017 Aug;45(8):1285-1294. doi: 10.1097/CCM.0000000000002441.
- Background: PubMed 25631669Angeli P, Gines P, Wong F, Bernardi M, Boyer TD, Gerbes A, Moreau R, Jalan R, Sarin SK, Piano S, Moore K, Lee SS, Durand F, Salerno F, Caraceni P, Kim WR, Arroyo V, Garcia-Tsao G; International Club of Ascites. Diagnosis and management of acute kidney injury in patients with cirrhosis: revised consensus recommendations of the International Club of Ascites. Gut. 2015 Apr;64(4):531-7. doi: 10.1136/gutjnl-2014-308874. Epub 2015 Jan 28. No abstract available.
- Background: PubMed 20677285Olthoff KM, Kulik L, Samstein B, Kaminski M, Abecassis M, Emond J, Shaked A, Christie JD. Validation of a current definition of early allograft dysfunction in liver transplant recipients and analysis of risk factors. Liver Transpl. 2010 Aug;16(8):943-9. doi: 10.1002/lt.22091.
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- Background: PubMed 28255614Kellum JA, Zarbock A, Nadim MK. What endpoints should be used for clinical studies in acute kidney injury? Intensive Care Med. 2017 Jun;43(6):901-903. doi: 10.1007/s00134-017-4732-1. Epub 2017 Mar 2. No abstract available.
- Background: PubMed 32609011Bellomo R, Forni LG, Busse LW, McCurdy MT, Ham KR, Boldt DW, Hastbacka J, Khanna AK, Albertson TE, Tumlin J, Storey K, Handisides D, Tidmarsh GF, Chawla LS, Ostermann M. Renin and Survival in Patients Given Angiotensin II for Catecholamine-Resistant Vasodilatory Shock. A Clinical Trial. Am J Respir Crit Care Med. 2020 Nov 1;202(9):1253-1261. doi: 10.1164/rccm.201911-2172OC.
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- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael P Bokoch, M.D., Ph.D. principal investigator
Department of Anesthesia and Perioperative Care, University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Angiotensin II and Saline in people with Liver Transplant; Complications and Vasoplegia, run by University of California, San Francisco at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 20 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04901169, which also lists 16 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2026.