Angiotensin II for Liver Transplant Complications

(AngLT-1 Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Michael 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. ^{1 2 3 4 5}

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. ^{1 2 3 4 6}

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. ^{1 2 3 7 8}

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.

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.

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 Overview This 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

Group I: Angiotensin II (Giapreza) Experimental Treatment 1 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: Saline Placebo Group 1 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

Research Locations Nearby Select from list below to view details:

University of California, San Francisco San Francisco, CA

Who Is Running the Clinical Trial?

University of California, San Francisco Lead Sponsor

La Jolla Pharmaceutical Company Industry Sponsor

References

1. United States pubmed.ncbi.nlm.nih.gov

Beneficial effect of angiotensin-blocking agents on graft fibrosis in hepatitis C recurrence after liver transplantation. [2022] Hepatitis C recurrence after liver transplantation is often associated with accelerated graft fibrosis and progression to cirrhosis. Because drugs blocking the action of angiotensin-II can reduce fibrosis in different human and experimental models, we assessed the possible beneficial effect of these drugs on graft fibrosis in hepatitis C recurrence after liver transplantation.

2. England pubmed.ncbi.nlm.nih.gov

Angiotensin II in liver transplantation (AngLT-1): protocol of a randomised, double-blind, placebo-controlled trial. [2023] Catecholamine vasopressors such as norepinephrine are the standard drugs used to maintain mean arterial pressure during liver transplantation. At high doses, catecholamines may impair organ perfusion. Angiotensin II is a peptide vasoconstrictor that may improve renal perfusion pressure and glomerular filtration rate, a haemodynamic profile that could reduce acute kidney injury. Angiotensin II is approved for vasodilatory shock but has not been rigorously evaluated for treatment of hypotension during liver transplantation. The objective is to assess the efficacy of angiotensin II as a second-line vasopressor infusion during liver transplantation. This trial will establish the efficacy of angiotensin II in decreasing the dose of norepinephrine to maintain adequate blood pressure. Completion of this study will allow design of a follow-up, multicentre trial powered to detect a reduction of organ injury in liver transplantation.

3. United States pubmed.ncbi.nlm.nih.gov

Angiotensin blockade does not affect fibrosis progression in recurrent hepatitis C after liver transplantation. [2013] Liver transplantation (LT) for hepatitis C virus (HCV)-related end-stage liver disease is impaired by universal disease recurrence and suboptimal response to antiviral therapy. Inhibition of angiotensin-II signalling by angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin-II receptor blockers (ARB) decreases hepatic stellate cell activation in vitro and hepatic fibrogenesis in animal models. A single-center retrospective analysis suggested that angiotensin blockade (AB) inhibits fibrosis progression in recurrent HCV post-LT. This study assessed the effect of AB on fibrosis progression in an independent patient cohort.

4. United States pubmed.ncbi.nlm.nih.gov

Effect of losartan, an angiotensin II receptor antagonist, on portal pressure in cirrhosis. [2022] Administration of angiotensin II causes an increase in portal pressure, and plasma concentration of angiotensin II is elevated in patients with cirrhosis, suggesting that angiotensin II may be involved in the pathogenesis of portal hypertension in cirrhosis. We evaluated the effect of the orally active angiotensin II receptor antagonist, losartan, on portal pressure in patients with cirrhosis and portal hypertension. Thirty patients with severe (hepatic venous pressure gradient [HVPG] >/= 20 mm Hg) and 15 patients with moderate (HVPG /= 20 mm Hg) and 10 (HVPG

5. Netherlands pubmed.ncbi.nlm.nih.gov

New angiotensin II type 1 receptor blocker olmesartan improves portal hypertension in patients with cirrhosis. [2020] To evaluate the effect of the new oral angiotensin II type 1 receptor blocker olmesartan on portal hemodynamics in patients with cirrhosis.

6. Romania pubmed.ncbi.nlm.nih.gov

The effect of valsartan, an angiotensin II receptor antagonist, on portal and systemic hemodynamics and on renal function in liver cirrhosis. [2015] The aim of the study was to assess the effects of valsartan, a new generation angiotensin II receptor antagonist, on portal and systemic hemodynamics and on renal function in cirrhosis.

7. United States pubmed.ncbi.nlm.nih.gov

Intraoperative Use of Angiotensin II for Severe Vasodilatory Shock During Liver Transplantation: A Case Report. [2021] Refractory hypotension is a known entity in liver transplantation. Catecholamine and vasopressin infusions are first-line therapies. There has been recent interest in angiotensin II (Ang-2) as an alternative vasopressor; however, liver failure patients were excluded from the original trials. Ang-2 has potential in this patient population. This case discusses a patient who received an infusion of Ang-2 during a liver transplant for combined liver failure-induced distributive shock and septic shock. It is the first known successful use of intraoperative Ang-2 in this situation, and it shows that Ang-2 may be safe in liver transplantation when traditional therapies fail.

8. United States pubmed.ncbi.nlm.nih.gov

Trauma- and sepsis-induced hepatic ischemia and reperfusion injury: role of angiotensin II. [2019] We hypothesized that angiotensin II, a potent vasoconstrictor, is involved in the occurrence of hepatic ischemia after burn and sepsis, and that administration of angiotensin II antagonist DuP753 would ameliorate this process.