Clinical trial NCT04048707: Angiotensin 2 for Hepatorenal Syndrome
Official title: Angiotensin 2 as a Novel Treatment for Hepatorenal Syndrome
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Hepatorenal Syndrome
Cirrhosis
Kidney Failure, Acute
Lead sponsor: University of California, Los Angeles
Sponsor class: OTHER
First posted: 2019-08-07
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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.

Primary outcomes:
measure: Reversal of hepatorenal syndrome
timeFrame: 4 days
Secondary outcomes:
measure: Need for renal replacement therapy
timeFrame: 4 days
measure: Mortality
timeFrame: 28 days
measure: Serum sodium
timeFrame: 4 days
measure: Relapse of hepatorenal syndrome
timeFrame: 14 days
Other outcomes:
Locations:
Study officials:
References:
citation: Tumlin JA, Murugan R, Deane AM, Ostermann M, Busse LW, Ham KR, Kashani K, Szerlip HM, Prowle JR, Bihorac A, Finkel KW, Zarbock A, Forni LG, Lynch SJ, Jensen J, Kroll S, Chawla LS, Tidmarsh GF, Bellomo R; Angiotensin II for the Treatment of High-Output Shock 3 (ATHOS-3) Investigators. Outcomes in Patients with Vasodilatory Shock and Renal Replacement Therapy Treated with Intravenous Angiotensin II. Crit Care Med. 2018 Jun;46(6):949-957. doi: 10.1097/CCM.0000000000003092.
citation: Khanna A, Ostermann M, Bellomo R. Angiotensin II for the Treatment of Vasodilatory Shock. N Engl J Med. 2017 Dec 28;377(26):2604. doi: 10.1056/NEJMc1714511. No abstract available.