Angiotensin 2 for Hepatorenal Syndrome (ANTHEM)
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|ClinicalTrials.gov Identifier: NCT04048707|
Recruitment Status : Not yet recruiting
First Posted : August 7, 2019
Last Update Posted : September 11, 2020
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.
|Condition or disease||Intervention/treatment||Phase|
|Hepatorenal Syndrome Cirrhosis Kidney Failure, Acute||Drug: Angiotensin II Drug: Midodrine Drug: Octreotide Drug: Albumin solution||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||48 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Angiotensin 2 as a Novel Treatment for Hepatorenal Syndrome|
|Estimated Study Start Date :||July 1, 2021|
|Estimated Primary Completion Date :||June 30, 2023|
|Estimated Study Completion Date :||July 1, 2023|
Active Comparator: Midodrine/Octreotide
This arm will receive standard of care treatment of midodrine, octreotide, and albumin.
Drug: Albumin solution
Experimental: Angiotensin 2
This arm will receive the experimental treatment of angiotensin 2 infusion and albumin.
Drug: Angiotensin II
Other Name: Giapreza
Drug: Albumin solution
- Reversal of hepatorenal syndrome [ Time Frame: 4 days ]
Partial or complete reversal of HRS. Serum creatinine will be measured daily and compared against the patient's baseline creatinine.
Partial reversal is defined defined as improvement of at least one AKI stage as defined by International Club of Ascites Acute Kidney Injury (ICA-AKI) criteria Complete defined as improvement of serum creatinine to within 0.3 mg/dl of baseline value).
- Stage 1: increase in sCr ≥0.3 mg/dl (26.5 μmol/L) or an increase in sCr ≥1.5-fold to 2-fold from baseline
- Stage 2: increase in sCr >2-fold to 3-fold from baseline
- Stage 3: increase of sCr >3-fold from baseline or sCr ≥4.0 mg/dl (353.6 μmol/L) with an acute increase ≥0.3 mg/dl (26.5 μmol/L) or initiation of renal replacement therapy Angeli P et al. J Hepatology 2015:62(968-974)
- Need for renal replacement therapy [ Time Frame: 4 days ]The treating team with the assistance of nephrology will assess the acute need for dialysis on a daily basis. If the patient does require urgent hemodialysis at their determination, this will be noted. The proportion of each group who required hemodialysis will be compared.
- Mortality [ Time Frame: 28 days ]In-hospital mortality
- Serum sodium [ Time Frame: 4 days ]Change in serum sodium from the beginning of the study to the end of the study.
- Relapse of hepatorenal syndrome [ Time Frame: 14 days ]Recurrence of HRS-AKI after withdrawal of study drug, defined as a worsening of AKI by at least one stage according to ICA-AKI criteria AKI grade as defined by ICA-AKI criteria (J Hepatology 2015:62[968-974])
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04048707
|Contact: Michael Y Lin, MDfirstname.lastname@example.org|