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A Study of OCE-205 in Participants With Cirrhosis With Ascites Who Developed Hepatorenal Syndrome-Acute Kidney Injury

Overview

About this study

The study aims are to evaluate the safety and effectiveness of OCE-205 at various doses. Participants will receive treatment by intravenous infusion and will continue this treatment until participants meet primary endpoint or any discontinuation criteria.  OCE-205 is being tested to treat participants who have developed Hepatorenal Syndrome-Acute Kidney Injury as a complication of cirrhosis with ascites.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

- Signed informed consent form (ICF) by participant or their legal/authorized
representatives.

- Diagnosed with decompensated cirrhosis with ascites.

- Receiving albumin and has had appropriate diuretic withdrawal for at least 2 days
prior to randomization into the study.

- Beta-blockers should be discontinued 48 hours prior to randomization, unless doctor
deems necessary for appropriate medical treatment.

- No sustained improvement in renal function after both diuretic withdrawal and plasma
volume expansion with albumin.

- Female participants must have a negative pregnancy test prior to randomization and
agree to avoid becoming pregnant during the study and for 30 days after the end of
treatment. Male participants must agree to use 2 effective contraceptive methods
during the study and up to 30 days after the end of treatment.

Exclusion Criteria:

- Serum Creatinine >3.8 mg/dL.

- Large volume paracentesis (LVP ≥6L) within 4 days of randomization.

- Pulse oximeter reading of <90% on 2L or less.

- Sepsis and/or uncontrolled bacterial infection.

- Experienced shock within 72 hrs prior to screening.

- Model for End-Stage Liver Disease (MELD) score >35.

- Hypertension with a Systolic BP > 140 mmHg and/ or a Diastolic BP >100 mmHg.

- Treated with or exposed to nephrotoxic agents or has had exposure to radiographic
contrast agents within 72 hrs prior to screening.

- Has superimposed acute liver injury due to drugs, or toxins except for acute alcoholic
hepatitis.

- Proteinuria greater than 500 mg/dL.

- Impaired cardiac function as evidenced by symptoms consistent with New York Heart
Association Classification Class 2 or worse.

- Received Renal Replacement Therapy (RRT) within 4 weeks of randomization.

- Has had a Trans Jugular Intrahepatic Porto-systemic shunt (TIPS).

- Pregnant or breastfeeding.

- Diagnosed with a malignancy within the past 5 years.

- History or current evidence of any condition (COVID-19 positive with
respiratory/cardiac complications), therapy or laboratory abnormality that might
confound the results of the study, interfere with the participation for the full
duration of the study, or is not in the best interest to participate in the opinion of
the investigator.

- Participated in a study of an investigational medical product or device within the
last 8 weeks preceding screening.

- Experienced a major blood loss (≥500 mL) within the last 4 weeks prior to screening.

- Is stuporous or comatose at screening (West Haven scores III and IV). exhibiting
bradycardia.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 5/18/23. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status

Rochester, Minn.

Mayo Clinic principal investigator

Douglas Simonetto, M.D.

Closed for enrollment

More information

Publications

  • The vasoconstrictor terlipressin is used for type 1 hepatorenal syndrome (HRS-1) in many parts of the world and is part of the clinical practice guidelines in Europe. Read More on PubMed
  • Hepatorenal syndrome (HRS) is a form of kidney function impairment that characteristically occurs in cirrhosis. Recent changes in terminology have led to acute HRS being referred to as acute kidney injury (AKI)-HRS and chronic HRS as chronic kidney disease (CKD)-HRS. AKI-HRS is characterized by a severe impairment of kidney function owing to vasoconstriction of the renal arteries in the absence of substantial abnormalities in kidney histology. Pathogenetic mechanisms involve disturbances in circulatory function due to a marked splanchnic arterial vasodilation, which triggers the activation of vasoconstrictor factors. An intense systemic inflammatory reaction that is characteristic of advanced cirrhosis may also be involved. The main triggering factors of AKI-HRS are bacterial infections, particularly spontaneous bacterial peritonitis. The diagnosis of AKI-HRS is a challenge because of a lack of specific diagnostic tools and mainly involves the differential diagnosis from other forms of AKI, particularly acute tubular necrosis. The prognosis of patients with AKI-HRS is poor, with a median survival of ≤3 months. The ideal treatment for AKI-HRS is liver transplantation in patients without contraindications. Medical therapy consists of vasoconstrictor drugs to counteract splanchnic arterial vasodilation together with volume expansion with albumin. Effective measures to prevent AKI-HRS include early identification and treatment of bacterial infections and the administration of albumin in patients with spontaneous bacterial peritonitis. Read More on PubMed
  • Hepatorenal syndrome type 1 (HRS-1) in patients with cirrhosis and ascites is a functional, potentially reversible, form of acute kidney injury characterized by rapid (<2 wk) and progressive deterioration of renal function. Terlipressin is a synthetic vasopressin analogue that acts, via vascular vasopressin V1 receptors, as a systemic vasoconstrictor. We performed a phase 3 study to evaluate the efficacy and safety of intravenous terlipressin plus albumin vs placebo plus albumin in patients with HRS-1. Read More on PubMed
  • Hepatorenal syndrome (HRS), a serious complication of cirrhosis, is associated with high mortality without treatment. Terlipressin with albumin is effective in the reversal of HRS. Where terlipressin is not available, as in the United States, midodrine and octreotide with albumin are used as an alternative treatment of HRS. The aim was to compare the effectiveness of terlipressin plus albumin versus midodrine and octreotide plus albumin in the treatment of HRS in a randomized controlled trial. Twenty-seven patients were randomized to receive terlipressin with albumin (TERLI group) and 22 to receive midodrine and octreotide plus albumin (MID/OCT group). The TERLI group received terlipressin by intravenous infusion, initially 3 mg/24 hours, progressively increased to 12 mg/24 hours if there was no response. The MID/OCT group received midodrine orally at an initial dose of 7.5 mg thrice daily, with the dose increased to a maximum of 12.5 mg thrice daily, together with octreotide subcutaneously: initial dose 100 μg thrice daily and up to 200 μg thrice daily. Both groups received albumin intravenously 1 g/kg of body weight on day 1 and 20-40 g/day thereafter. There was a significantly higher rate of recovery of renal function in the TERLI group (19/27, 70.4%) compared to the MID/OCT group (6/21, 28.6%), P = 0.01. Improvement in renal function and lower baseline Model for End-Stage Liver Disease score were associated with better survival. Read More on PubMed
  • Hepatorenal syndrome (HRS) is a serious complication of end-stage liver disease, occurring mainly in patients with advanced cirrhosis and ascites, who have marked circulatory dysfunction,1 as well as in patients with acute liver failure.2 In spite of its functional nature, HRS is associated with a poor prognosis,3 4 and the only effective treatment is liver transplantation. During the 56th Meeting of the American Association for the Study of Liver Diseases, the International Ascites Club held a Focused Study Group (FSG) on HRS for the purpose of reporting the results of an international workshop and to reach a consensus on a new definition, criteria for diagnosis and recommendations on HRS treatment. A similar workshop was held in Chicago in 1994 in which standardised nomenclature and diagnostic criteria for refractory ascites and HRS were established.5 The introduction of innovative treatments and improvements in our understanding of the pathogenesis of HRS during the previous decade led to an increasing need to undertake a new consensus meeting. This paper reports the scientific rationale behind the new definitions and recommendations. The international workshop included four issues debated by four panels of experts (see Acknowledgements). The issues were: (1) evidence-based HRS pathogenesis; (2) treatment of HRS using vasoconstrictors; (3) other HRS treatments using transjugular intrahepatic portosystemic stent-shunt (TIPS) and extracorporeal albumin dialysis (ECAD); and (4) new definitions and diagnostic criteria for HRS and recommendations for its treatment. Read More on PubMed
  • Hepatorenal syndrome (HRS) type 1 is a progressive functional renal failure in subjects with advanced liver disease. The aim of this study was to evaluate the efficacy and safety of terlipressin, a systemic arterial vasoconstrictor, for cirrhosis type 1 HRS. Read More on PubMed
  • Hepatorenal syndrome is common in patients with advanced cirrhosis and constitutes a major problem in liver transplantation. There is no effective medical treatment for hepatorenal syndrome. Read More on PubMed

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