A Study Evaluating the Utility of Ambrisentan in Lowering Portal Pressure in Patients With Liver Cirrhosis

Noorik Biopharmaceuticals

Status and phase

Terminated

Phase 2

Conditions

Portal Hypertension

Cirrhosis

Ascites

Treatments

Drug: Ambrisentan

Study type

Interventional

Funder types

Industry

Identifiers

NCT03827200

2018-002088-25 (EudraCT Number)

N-003-CRD003

Details and patient eligibility

About

Endothelin is a human hormone which has been associated with increased portal pressure in patients with liver cirrhosis (also called portal hypertension). Ambrisentan blocks the effects of endothelin. The purpose of this study is to evaluate the effect of ambrisentan on portal pressure and renal function in patients with advanced liver cirrhosis and with portal hypertension. In this study, portal pressure will be determined at multiple times with the aid of a catheter inserted into the body of the patient. The effect of ambrisentan on the function of the kidney will also be investigated. This study will also evaluate the concentrations of ambrisentan in blood in patients with liver cirrhosis.

Enrollment

19 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Signed informed consent including data protection declaration prior to study participation
Subjects with confirmed cirrhosis (by biopsy, ultrasound, and/or laboratory examinations)
Ascites Grade II or Grade III at screening currently treated with at least one diuretic or the subject is considered intolerant to diuretics in the investigator's opinion

Exclusion criteria

Age <18 years of age
Any of the following laboratory findings at the time of screening
- Serum creatinine level >1.5mg/dL (>132 µmol/L)
- Serum Na+ < 125 meq/L
- Serum K+ ≥ 5.5 meq/L
- Serum bilirubin ≥ 5 mg/dL (85.5 µmol/L)
- INR >3.0
Women of childbearing potential with no effective contraceptive method (women of childbearing potential [pre-menopausal, not surgically sterile for at least 3 months prior to the time of screening] must have a confirmed negative serum β-hCG pregnancy test prior to enrolment and at Baseline Visit. They must use an effective contraceptive method throughout the study, and agree to repeat serum β-hCG pregnancy tests at designated visits)
Pregnancy or lactation
Systolic blood pressure <90 mmHg or diastolic blood pressure <60 mmHg
Sepsis and/or uncontrolled bacterial infection
Current or recent documented nephrotoxicity (within 4 weeks)
Hepatic Encephalopathy above grade 1
History of variceal bleeding in the last 2 months
Suspicion of active alcohol consumption in the last 3 months
History of liver or kidney transplantation
History of Transjugular Intrahepatic Portosystemic Shunt (TIPS)
Suspected occlusive portal vein or splenic vein thrombosis
Hepatocellular carcinoma (HCC) beyond the Milan criteria
Acute Liver Failure or superimposed acute liver injury due to drugs (e.g., acetaminophen), dietary supplements, herbal preparations, viral hepatitis, or toxins
Severe cardiovascular disease, including, but not limited to, unstable angina, pulmonary oedema, congestive heart failure
Current or recent (within 30 days) renal replacement therapy (RRT)
If on beta-blockers, a change in dose or drug within last 15 days prior to screening
Use of any other endothelin receptor antagonist, octreotide, midodrine, terlipressin in last 15 days prior to screening
Known hypersensitivity to contrast-media
Any clinically significant abnormality identified on physical examination, laboratory tests, ECG or vital signs at the time of screening that in the judgment of the investigator or any sub-investigator would preclude safe completion of the study or constrains the assessment of efficacy
Known sensitivity to ambrisentan or any of the excipients of the formulation
Participation in other clinical research involving investigational medicinal products within 30 days of enrolment
Subjects who have difficulties in understanding the language in which the study information is given
Subjects who do not agree to the transmission of their anonymous data within the liability of documentation and notification
Staff of the study centre, staff of the sponsor or Clinical Research Organization (CRO), the investigator himself or close relatives of the investigator.

Cardiac and Pulmonary Haemodynamic Study exclusion Criteria: Subjects fulfilling any of the exclusion criteria below may participate in the study, but will not undergo cardiac and pulmonary catheterisation:

Significant arrhythmias, which include any of the following: sustained ventricular tachycardia, bradycardia with sustained ventricular rate < 45 beats per minute or atrial fibrillation/flutter with sustained ventricular response of > 90 beats per minute at rest, or Long QT syndrome or QTc > 450 ms
Significant left ventricular outflow tract obstructions (e.g., severe valvular aortic stenosis, obstructive cardiomyopathy), severe mitral stenosis, restrictive amyloid myocardiopathy, acute myocarditis
Severe aortic insufficiency or severe mitral regurgitation for which surgical or percutaneous intervention is indicated
Major neurologic event including cerebrovascular events, within 30 days prior to screening
Clinical evidence of acute coronary syndrome currently or within 30 days prior to screening
Permanent pacemaker, cardiac resynchronisation device or implantable cardioverter-defibrillator in situ