Angiotensin 2 for AKI After OLT

NCT04592744 | Enrolling By Invitation Phase 4 DMC FDA Drug

• 1 other identifier: 20-001402
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Kidney injury is a common complication following liver transplantation and is associated with a higher complication rate and increased risk of death. While there are many factors that likely contribute to kidney injury in the perioperative period, a relative low serum level of angiotensin 2 (Ang 2) (a protein hormone that causes blood vessels to narrow) found in patients with liver cirrhosis (late stage of liver damage) may increase their risk of developing acute kidney injury (sudden episode of kidney failure or damage). We propose to investigate how early administration of Ang 2, a new vasopressor drug approved by the FDA in December 2017 for patients with low blood pressure, during the intra-operative period of liver transplant surgery affects the rate of kidney injury after transplantation. Patients who are deemed appropriate candidates for the study will be randomized 1:1 to the treatment and control groups. The intervention period of the study will occur in the operating room during transplant surgery and will be performed by their anesthesiologists. In the Treatment group, patients will receive Ang 2 infusions in addition to other standard vasopressors while patients in the control group will receive standard vasopressors alone. The infusion of Ang 2 in the treatment group will continue through the duration of the surgery and will be stopped prior to leaving the operating room. Both the treatment group and the control group will then be followed for 14 days to evaluate rates of kidney injury and to look for any complications. The follow up period will be extended to 28 days to look at in-hospital mortality rates in both groups. The daily follow up analysis will occur while the enrolled patients are inpatient following their transplantation surgery and will be done by looking at lab values and other data that is routinely gathered by their managing teams. This study will serve as a pilot study to evaluate feasibility of our protocol and to collect some preliminary data on the use of Ang 2 in this patient population. As such we plan to enroll approximately 30 patients who have accepted an offer to receive a donor liver. We hope to reach our goal enrollment within 5 months of starting the study.

Conditions

Cirrhosis, Liver; End Stage Liver DIsease; Acute Kidney Injury; Liver Transplant; Complications

Outcome Measures

Primary Outcomes (1)

• Incidence of Acute kidney Injury

  Measured by change in serum creatinine from baseline based on KDIGO criteria.

  Every day for 14 days following intervention

Secondary Outcomes (5)

• Need for Renal Replacement therapies

  Every day for 14 days following intervention

• In hospital mortalituy

  28 days

• Urine output

  14 days

• Vasopressor doses

  14 days

• Adverse events

  14 days

Study Arms (2)

Intervention

EXPERIMENTAL

Patients assigned to the study group will receive Ang 2 infusion in addition to standard vasopressor regimen. Ang 2 is currently approved at UCLA as a second line vasopressor and will be used as such for the purposes of our study. Hemodynamic goals will be established at the beginning of the case by the anesthesiology and surgical teams. Ang 2 will be started as a second vasopressor once the norepinephrine dose has reached 0.05mcg/kg/min. Ang 2 will be initiated at a starting dose of 5ng/kg/min. That dose will be up titrated one time to 10ng/kg/min as vasopressor requirements escalate. Once a patient is on the 10ng/kg/min dose of ang 2, no additional up titration will be performed. Hemodynamic management will continue throughout the case with titration of other vasopressors as needed. Ang 2 will be continued throughout the intraoperative period but will be weaned off prior to leaving the operating room.

Drug: Angiotensin II; Drug: Norepinephrine

Control

ACTIVE COMPARATOR

Patients assigned to the control group will undergo intraoperative management with a standard vasopressor regimen composed of norepinephrine, vasopressin and epinephrine based on hemodynamic goals established by the surgical and anesthesia teams prior to surgery.

Drug: Norepinephrine

Interventions

Angiotensin II DRUG

Angiotensin II infusion for Intraoperative management during liver transplantation

Intervention

Norepinephrine DRUG

Vasopressor infusion for management of Intraoperative hypotension in liver transplantation.

Also known as: Vasopressin, Epinephrine

Control; Intervention

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A. End stage liver disease (ESLD) with acceptance of organ allocation offer. B. Stable renal function in the 48 hours prior to transplant (defined as \< 30% change in serum creatinine) C. Adult patients \> 18 years old

You may not qualify if:

• A. Active use of renal replacement therapies B. Recent (within last 3 months) history of CVA or MI C. Patients with hypercoagulable state as evidenced by pre-existing venous thromboembolism or known thrombophilia (Antiphospholipid syndrome, Factor V- Leiden etc.) D. Combined liver transplant and intrathoracic surgery cases (not including chest tube placement) E. Multiple organ transplantation F. Congestive heart failure defined as left ventricular ejection fraction \<45% G. Inability to obtain consent from the patient or surrogate H. Known allergy or sensitivity to any study medication I. Hepatocellular Carcinoma

Sponsors & Collaborators

• University of California, Los Angeles: lead

Study Sites (1)

Ronald Reagan UCLA Medical Center, Department of Anesthesiology & Perioperative Medicine

Los Angeles, California, 90095, United States

Location

Related Publications (2)

• 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.

  PMID: 28528561 BACKGROUND

• Tumlin 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.

  PMID: 29509568 BACKGROUND

MeSH Terms

Conditions

Liver Cirrhosis; End Stage Liver Disease; Acute Kidney Injury

Interventions

Angiotensin II; Norepinephrine; Vasopressins; Epinephrine

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Liver Failure; Hepatic Insufficiency; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Angiotensins; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Autacoids; Inflammation Mediators; Biological Factors; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Biogenic Monoamines; Biogenic Amines; Catecholamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Pituitary Hormones, Posterior; Pituitary Hormones

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Clinical Professor

Model Details: Patients will be randomized to the intervention group receiving angiotensin 2 in addition to standard vasopressors or to the control group in which patients will receive standard vasopressors alone.

Study Record Dates

• First Submitted: October 14, 2020
• First Posted: October 19, 2020
• Study Start: April 8, 2022
• Primary Completion: December 1, 2025
• Study Completion: March 1, 2026
• Last Updated: September 12, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)