Angiotensin 2 for Hepatorenal Syndrome (ANTHEM)

University of California, Los Angeles (UCLA)

Status and phase: Withdrawn; Phase 2

Conditions: Cirrhosis; Kidney Failure, Acute; Hepatorenal Syndrome

Treatments: Drug: Albumin solution; Drug: Midodrine; Drug: Octreotide; Drug: Angiotensin II

Study type: Interventional

Funder types: Other

Identifiers

NCT04048707

#19-005718

Details and patient eligibility

About

Hepatorenal syndrome (HRS) is a disease in which patients with cirrhosis (end stage liver failure) develop secondary kidney injury and failure. The current treatment available in the United States is a combination of octreotide and midodrine, which are meant to decrease the release of those hormones and raise the blood pressure, respectively, which would increase blood flow to the kidneys. Angiotensin 2 (Ang2) is a new vasopressor drug that was approved by the FDA in December 2017 for patients with low blood pressure and has been shown to have similar effects to octreotide and midodrine.

This study will investigate whether Ang2 reverses HRS among patients admitted to the intensive care unit (ICU) at Ronald Reagan Medical Center. Our study population will be patients with HRS who are already or will be admitted to the ICU. HRS will be defined by new internationally accepted guidelines published by the International Club of Ascites. All patients who are consented will undergo an Ang2 response trial, where low-dose Ang2 will be administered for 4 hours to see how the patients respond. This will help us characterize the nature of the patients' kidney failure for later analysis. Patients will then be randomized into the control group or the study group. Patients in the control group will receive octreotide (a subcutaneous injection) and midodrine (an oral drug). Patients in the study group will continue receiving intravenous infusion of Ang2. Patients in both groups will also receive albumin, a protein found commonly in human blood. Treatment will continue in both groups for four days, until complete reversal of HRS, dialysis, or death.

Our primary outcome will be rate of reversal of HRS, defined as improvement in kidney function.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria: Patients in the ICU with HRS-AKI defined as

• Acute kidney injury defined as an increase in serum creatinine (sCr) >=0.3 mg/dl or >=50% from baseline within 7 days
• Presence of cirrhosis and ascites
• Absence of other causes such as shock, nephrotoxic drugs, or other suspected causes of kidney injury.
• Lack of response to diuretic withdrawal and albumin challenge of 1 g/kg of body weight

Exclusion Criteria:

• Age <18 years
• Current or anticipated (within 24 hours) need for renal replacement therapy (RRT)
• Cr > 6 mg/dl
• Renal transplantation status
• Fractional Excretion of Sodium (FeNa) > 2%
• Pregnancy
• Recent Cerebrovascular Accident (CVA), Myocardial Infarction (MI), venous or arterial thrombosis (within last 3 months)
• Known hypercoagulable state other than cirrhosis
• Uncontrolled hypertension (SBP > 160)
• Anticipated mortality within 72 hours
• Inability to obtain consent.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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0 participants in 2 patient groups

Midodrine/Octreotide

Active Comparator group

Description:

This arm will receive standard of care treatment of midodrine, octreotide, and albumin.

Treatment:

Drug: Octreotide

Drug: Midodrine

Drug: Albumin solution

Angiotensin 2

Experimental group

Description:

This arm will receive the experimental treatment of angiotensin 2 infusion and albumin.

Treatment:

Drug: Angiotensin II

Drug: Albumin solution