What side effects are associated with this type of intervention?

Common treatments for Vasoplegic Syndrome, such as Angiotensin II, primarily aim to increase blood pressure through vasoconstriction and sodium retention. Known side effects of Angiotensin II include potential increases in blood pressure, reduced plasma renin activity, and decreased muscle sympathetic nerve activity. Other side effects may include hyperkalemia, renal impairment, and potential allergic reactions. It is important to monitor patients closely for these adverse effects during treatment.

What prior FDA approvals exist?

The FDA has approved several vasopressors for the treatment of vasoplegic syndrome, which is characterized by severe hypotension and vasodilation. Notably, Angiotensin II (brand name Giapreza) has been approved for use in patients with septic or other distributive shock to increase blood pressure. Other commonly used vasopressors include norepinephrine, vasopressin, and dopamine, which act through different mechanisms to induce vasoconstriction and improve blood pressure. These treatments are critical in managing vasoplegic syndrome, especially in settings like liver transplantation where maintaining adequate blood pressure is essential.

What other types of research exist?

Promising alternatives to Angiotensin II for treating Vasoplegic Syndrome in 2024 include phosphodiesterase-5 inhibitors (e.g., sildenafil), soluble guanylate cyclase stimulators (e.g., vericiguat), and endothelin antagonists (e.g., bosentan and macitentan). Mechanical circulatory support devices may also be considered for severe cases.

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Angiotensin II for Liver Transplant Complications (AngLT-1 Trial)

Phase 2 & 3

Recruiting

Led By Erika L Brinson, M.D.

Research Sponsored by University of California, San Francisco

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patient requiring > 0.05 mcg/kg/min of norepinephrine (NE) during LT

Liver transplantation from a deceased donor

Must not have

History of thrombotic or embolic disease, inherited hypercoagulable disorder, or therapeutic anticoagulation

Celiac stenosis

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 1 year

Summary

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.

Who is the study for?

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.

What is being tested?

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).

What are the potential side effects?

Angiotensin II may cause side effects such as increased blood pressure that could lead to potential complications like abnormal heart rhythms or damage to organs due to excessive constriction of the blood vessels.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I need a specific medication at a certain rate during my lung treatment.

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I received a liver transplant from a deceased donor.

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I am 18 years old or older.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a history of blood clots or am on blood thinners.

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I have a narrowing in my celiac artery.

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I have received a liver transplant from a living donor.

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I am receiving a part of a liver in my transplant.

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I have high blood pressure in the lungs due to liver issues.

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My organ donation will be after heart stops, without a warming machine.

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I have a blood clot in the vein to my liver.

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I was on a breathing machine before my lung transplant surgery.

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I am currently experiencing severe asthma or wheezing.

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I am experiencing sudden liver failure.

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I have had a liver transplant before.

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My heart's pumping ability is reduced.

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I have advanced kidney disease requiring regular dialysis.

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I have a history of Raynaud's disease.

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I am listed for or am receiving a liver and kidney transplant at the same time.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 1 year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~1 year

This trial's timeline: 3 weeks for screening, Varies for treatment, and 1 year for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

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.

Secondary study objectives

Body Weight Changes

Change in intraoperative urine output in mL/kg/hr before and after initiation of study drug

Dose of epinephrine administered during LT, excluding boluses within the 5 min immediately following portal reperfusion, averaged over case duration and TBW.

+12 more

Trial Design

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Angiotensin II

2010

Completed Phase 4

~260

0 / 18Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Vasoplegic Syndrome is characterized by severe vasodilation and low blood pressure, often occurring during surgeries like liver transplantation. Common treatments include vasopressors such as norepinephrine, vasopressin, and angiotensin II. These agents work by constricting blood vessels, thereby increasing vascular resistance and blood pressure. Angiotensin II, specifically, also promotes sodium retention, which helps to increase blood volume and further support blood pressure. These mechanisms are crucial for Vasoplegic Syndrome patients as they help to stabilize hemodynamics, ensuring adequate tissue perfusion and oxygenation during critical periods.

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