Status:

TERMINATED

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

Lead Sponsor:

Noorik Biopharmaceuticals AG

Conditions:

Cirrhosis

Portal Hypertension

Eligibility:

All Genders

18+ years

Phase:

PHASE2

Brief Summary

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....

Eligibility Criteria

Inclusion

  • 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

  • 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

Key Trial Info

Start Date :

April 11 2019

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

January 21 2021

Estimated Enrollment :

19 Patients enrolled

Trial Details

Trial ID

NCT03827200

Start Date

April 11 2019

End Date

January 21 2021

Last Update

February 26 2021

Active Locations (6)

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Page 1 of 2 (6 locations)

1

Hospital Clinic Barcelona

Barcelona, Catalonia, Spain, 08036

2

Hospital Universitario Puerta de Hierro-Majadahonda

Majadahonda, Madrid, Spain, 28222

3

Vall d'Hebron University Hospital

Barcelona, Spain, 08035

4

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain, 08041