Angiotensin II for AKI after Liver Transplantation

Enrolling by invitation at 1 trial location

Overseen By Michael Lin, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of California, Los Angeles

Disqualifiers: Renal replacement, CVA, MI, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a drug called Angiotensin II can prevent kidney problems in people after a liver transplant. Kidney injury often occurs post-transplant, and researchers aim to determine if early use of this drug during surgery can reduce the risk. Participants will receive either the drug with standard treatment or just the standard treatment. This trial may suit individuals with serious liver disease scheduled for a liver transplant and who have stable kidney function. As a Phase 4 trial, this research seeks to understand how this FDA-approved and effective treatment can benefit more patients.

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What is the safety track record for Angiotensin II and Norepinephrine?

Research has shown that angiotensin II (Ang 2), a medication approved by the FDA for treating low blood pressure, is generally safe. Studies have found it effective for patients undergoing liver transplants. Patients who received Ang 2 did not report major side effects, indicating its safety for this use.

Since the trial is in a later phase, the treatment has already passed initial safety tests. This means Ang 2 is considered safe enough for more extensive testing in specific situations, such as after liver transplants. Prospective participants can be reassured that Ang 2 has been used safely in similar cases. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard of care for acute kidney injury (AKI) after liver transplantation, which typically includes vasopressors like norepinephrine, angiotensin II (Ang 2) offers a unique mechanism by directly targeting and constricting blood vessels to improve blood pressure. Researchers are excited about Ang 2 because it acts as a second-line vasopressor and might provide more precise hemodynamic control. This targeted approach could help stabilize patients more effectively during surgery, potentially leading to better outcomes compared to the usual treatment options.

What evidence suggests that Angiotensin II might be an effective treatment for acute kidney injury after liver transplantation?

Research shows that Angiotensin II (Ang 2), which participants in this trial may receive, can help control blood pressure during liver transplants, potentially lowering the risk of sudden kidney problems. Earlier studies found that Ang 2 reduces the need for other blood pressure drugs, like norepinephrine, during surgery. Maintaining steady blood pressure is crucial to avoid kidney issues. Additionally, studies have shown that using Ang 2 in liver transplants supports kidney health by helping blood vessels remain properly tightened. While Ang 2 is already approved for treating low blood pressure, ongoing research aims to better understand its potential to reduce kidney problems after liver transplants. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with end-stage liver disease who are about to receive a liver transplant and have had stable kidney function in the last 48 hours. It's not for those on dialysis, recent stroke or heart attack survivors, people with clotting disorders, heart failure patients, or those allergic to study drugs.

Inclusion Criteria

My kidney function has been stable for the last 2 days.

I am older than 18 years.

I have end-stage liver disease and have been accepted for a liver transplant.

Exclusion Criteria

I have not had a stroke or heart attack in the last 3 months.

I have had more than one organ transplant.

I am currently on dialysis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Intraoperative Treatment

Participants receive Angiotensin 2 infusions during liver transplant surgery

Duration of surgery

1 visit (in-person, during surgery)

Follow-up

Participants are monitored for safety and effectiveness after treatment

28 days

Daily follow-up while inpatient

What Are the Treatments Tested in This Trial?

Interventions

• Angiotensin II
• Norepinephrine

Trial Overview The trial tests if Angiotensin II (Ang 2), a new vasopressor drug given during liver transplant surgery can reduce kidney injury after the operation. Patients will be randomly assigned to either get Ang 2 plus standard treatment or just standard treatment alone.

How Is the Trial Designed?

Group I: Intervention Experimental Treatment 2 Interventions

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.

Group II: Control Active Control 1 Intervention

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.

Angiotensin II is already approved in United States for the following indications:

Approved in United States as Giapreza for:

• Septic shock
• Vasodilatory shock

Who Is Running the Clinical Trial?

University of California, Los Angeles

Lead Sponsor

Trials

1,594

Recruited

10,430,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10660907/

Angiotensin II in liver transplantation (AngLT-1): protocol of a ... Acute kidney injury after LT significantly reduces patient and graft survival. Reducing catecholamine dose by adding a vasopressor with a ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04901169

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 ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37984940/

Angiotensin II in liver transplantation (AngLT-1) - PubMed - NIH This trial will establish the efficacy of angiotensin II in decreasing the dose of norepinephrine to maintain adequate blood pressure.

4. amjtransplant.org amjtransplant.org/article/S1600-6135(25)01459-5/pdf

Clinical Application of Angiotensin II for Hemodynamic ... Results: The study included a total of 90 liver transplant recipients, 43 (48%) developed acute kidney injury (AKI), with Stage 1 (65%) being the most common,.

5. bmjopen.bmj.com bmjopen.bmj.com/content/bmjopen/13/11/e078713.draft-revisions.pdf

BMJ Open is committed to open peer review. As ... acute kidney injury after liver transplantation. 11. Methods and analysis: This is a double-blind, randomized clinical trial. Eligible subjects ...

6. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/acute-kidney-injury

UCSF Acute Kidney Injury Clinical Trials for 2025 The goal of the LIBERATE-D clinical trial is to improve outcomes for patients recovering from dialysis-requiring acute kidney injury (AKI-D).