~5 spots leftby Sep 2025

Angiotensin II for Liver Transplant Complications

(AngLT-1 Trial)

MP
Overseen byMichael P Bokoch, M.D., Ph.D.
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2 & 3
Recruiting
Sponsor: University of California, San Francisco
Must be taking: Norepinephrine
Must not be taking: Angiotensin blockers
Disqualifiers: Acute liver failure, Renal disease, others
Prior Safety Data
Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This trial is testing Angiotensin II, a drug that raises blood pressure, in liver transplant patients who need extra support to maintain their blood pressure. The drug works by tightening blood vessels to improve blood flow and increase blood pressure. Angiotensin II (ANG-2) is of increasing interest as an additional treatment to traditional therapy, both for improvement in blood pressure and for reducing the use of high-dose medications.

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

The trial requires that you stop taking angiotensin II receptor blockers or angiotensin converting enzyme inhibitors at least 48 hours before participating. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

What data supports the effectiveness of the drug Angiotensin II, Giapreza for liver transplant complications?

Research suggests that Angiotensin II can improve blood flow to the kidneys during liver transplantation, which might help reduce kidney injury. Additionally, drugs that block Angiotensin II have shown potential in reducing liver fibrosis in some studies, although results are mixed.12345

Is Angiotensin II safe for use in humans?

Angiotensin II is approved for use in vasodilatory shock, indicating it has been evaluated for safety in humans. However, its safety specifically during liver transplantation is still being studied.12346

How does the drug angiotensin II differ from other treatments for liver transplant complications?

Angiotensin II is unique because it is a peptide vasoconstrictor that may improve kidney function by enhancing blood flow to the kidneys, potentially reducing acute kidney injury during liver transplantation. Unlike standard catecholamine vasopressors, which can impair organ perfusion at high doses, angiotensin II is being evaluated as a second-line option to maintain blood pressure with potentially fewer side effects.12378

Research Team

MP

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

Principal Investigator

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

Eligibility Criteria

Adults over 18 needing a liver transplant from a deceased donor with severe liver disease (MELD-Na score >=25) can join. They must need certain blood pressure support during the transplant. Excluded are those with portal vein thrombosis, angiotensin II allergy, pre-transplant ventilation, other safety or data quality risks, active bronchospasm, specific types of transplants or re-transplants, recent certain heart or blood pressure meds use, portopulmonary hypertension, significant heart dysfunction, clotting disorders or anticoagulation therapy.

Inclusion Criteria

I need a specific medication at a certain rate during my lung treatment.
I received a liver transplant from a deceased donor.
Your MELD-Na score is 25 or higher at the time of transplant.
See 1 more

Exclusion Criteria

I have a history of blood clots or am on blood thinners.
I have a narrowing in my celiac artery.
I have taken blood pressure medication before surgery.
See 15 more

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Angiotensin II or placebo during liver transplantation to manage blood pressure

Duration of surgery (approximately 8 hours)

Follow-up

Participants are monitored for safety and effectiveness after liver transplantation

Up to 1 year

Hospital Stay

Participants remain in the hospital for recovery and monitoring post-transplantation

Up to 1 year

Treatment Details

Interventions

  • Angiotensin II (Vasopressor)
Trial OverviewThis trial tests Angiotensin II as an additional medication to increase blood pressure in patients undergoing liver transplantation who aren't responding well enough to standard treatments. It compares its effectiveness and safety against saline (a placebo).
Participant Groups
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Angiotensin II (Giapreza)Experimental Treatment1 Intervention
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 II: SalinePlacebo Group1 Intervention
Sterile 0.9% saline, initiated and titrated at an equivalent volume infusion rate to the study drug, administered by continuous intravenous infusion.

Find a Clinic Near You

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials
2,636
Recruited
19,080,000+

La Jolla Pharmaceutical Company

Industry Sponsor

Trials
24
Recruited
2,700+

Findings from Research

In a study of 128 liver transplant recipients with hepatitis C recurrence, those treated with angiotensin-blocking agents had a significantly lower incidence of cirrhosis in the graft compared to those who did not receive these medications (15% vs. 35%).
Patients on angiotensin-blocking agents also showed lower fibrosis stages and slower progression of fibrosis over time, suggesting these drugs may help protect against graft fibrosis after liver transplantation.
Beneficial effect of angiotensin-blocking agents on graft fibrosis in hepatitis C recurrence after liver transplantation.Rimola, A., Londoño, MC., Guevara, G., et al.[2022]
This clinical trial aims to evaluate the efficacy of angiotensin II as a second-line vasopressor during liver transplantation, potentially allowing for a reduction in the dose of norepinephrine needed to maintain adequate blood pressure in patients with severe liver disease.
The study will assess not only the primary outcome of norepinephrine dosage but also safety outcomes like thromboembolism and severe hypertension, ensuring a comprehensive evaluation of angiotensin II's impact on patient safety and organ perfusion.
Angiotensin II in liver transplantation (AngLT-1): protocol of a randomised, double-blind, placebo-controlled trial.Bokoch, MP., Tran, AT., Brinson, EL., et al.[2023]
In a study of 109 patients who underwent liver transplantation for hepatitis C, the use of angiotensin blockade (ACE-I/ARB) did not show a significant reduction in fibrosis progression compared to those not treated with these medications.
Despite previous suggestions that angiotensin blockade might inhibit fibrosis progression in recurrent hepatitis C post-transplant, this study found no difference in fibrosis rates or progression between the two groups over a median follow-up of 23 months.
Angiotensin blockade does not affect fibrosis progression in recurrent hepatitis C after liver transplantation.Guillaud, O., Gurram, KC., Puglia, M., et al.[2013]

References

Beneficial effect of angiotensin-blocking agents on graft fibrosis in hepatitis C recurrence after liver transplantation. [2022]
Angiotensin II in liver transplantation (AngLT-1): protocol of a randomised, double-blind, placebo-controlled trial. [2023]
Angiotensin blockade does not affect fibrosis progression in recurrent hepatitis C after liver transplantation. [2013]
Effect of losartan, an angiotensin II receptor antagonist, on portal pressure in cirrhosis. [2022]
New angiotensin II type 1 receptor blocker olmesartan improves portal hypertension in patients with cirrhosis. [2020]
The effect of valsartan, an angiotensin II receptor antagonist, on portal and systemic hemodynamics and on renal function in liver cirrhosis. [2015]
Intraoperative Use of Angiotensin II for Severe Vasodilatory Shock During Liver Transplantation: A Case Report. [2021]
Trauma- and sepsis-induced hepatic ischemia and reperfusion injury: role of angiotensin II. [2019]