NCT03827200

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. 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.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
19

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Apr 2019

Geographic Reach
1 country

6 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 25, 2019

Completed
7 days until next milestone

First Posted

Study publicly available on registry

February 1, 2019

Completed
2 months until next milestone

Study Start

First participant enrolled

April 11, 2019

Completed
1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 29, 2020

Completed
23 days until next milestone

Study Completion

Last participant's last visit for all outcomes

January 21, 2021

Completed
Last Updated

February 26, 2021

Status Verified

February 1, 2021

Enrollment Period

1.7 years

First QC Date

January 25, 2019

Last Update Submit

February 23, 2021

Conditions

Keywords

CirrhosisPortal HypertensionAmbrisentanN-003Hepatic Vein Pressure GradientHVPGRefractory AscitesVarices, EsophagealVariceal HemorrhageHepatitis BHepatitis CNon-Alcoholic Fatty Liver DiseaseNon-alcoholic SteatohepatitisAscites

Outcome Measures

Primary Outcomes (1)

  • Mean change in Hepatic Vein Pressure Gradient (HVPG) from Baseline to Day 14

    Baseline HVPG is defined as the HVPG assessment performed prior to the first study drug administration. Day 14 HVPG is defined as the HVPG assessment prior to the last dose of study drug. The mean change in HVPG will be calculated as the difference between the HVPG assessment performed at Day 14 and the HVPG assessment performed at baseline

    14 Days

Secondary Outcomes (10)

  • Change in 24-hour Urinary Sodium Volume (UNaV)

    48 hours

  • Change in weight

    28 days

  • Change in abdominal girth

    28 days

  • Change in Model of End-Stage Liver Disease (MELD) score

    28 days

  • Change in Child-Pugh score

    28 days

  • +5 more secondary outcomes

Other Outcomes (4)

  • Proportion of patients achieving a 20% reduction in HVPG at Day 14 from baseline

    14 days

  • Proportion of patients achieving a 10% reduction in HVPG at Day 14 from baseline

    14 days

  • Proportion of patients achieving an HVPG of 10 mmHg or less at Day 14 from baseline

    14 days

  • +1 more other outcomes

Study Arms (1)

Ambrisentan

EXPERIMENTAL

Ambrisentan

Drug: Ambrisentan

Interventions

Ambrisentan will be administered subcutaneously at the Hospital on the days of HVPG deterination and taken orally at home between visits.

Also known as: N-003
Ambrisentan

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • +22 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

Hospital Clinic Barcelona

Barcelona, Catalonia, 08036, Spain

Location

Hospital Universitario Puerta de Hierro-Majadahonda

Majadahonda, Madrid, 28222, Spain

Location

Vall d'Hebron University Hospital

Barcelona, 08035, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08041, Spain

Location

Hospital Universitario Gregorio Marañón

Madrid, 28007, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

MeSH Terms

Conditions

FibrosisHypertension, PortalAscitesEsophageal and Gastric VaricesHepatitis BHepatitis CNon-alcoholic Fatty Liver Disease

Interventions

ambrisentan

Condition Hierarchy (Ancestors)

Pathologic ProcessesPathological Conditions, Signs and SymptomsLiver DiseasesDigestive System DiseasesEsophageal DiseasesGastrointestinal DiseasesBlood-Borne InfectionsCommunicable DiseasesInfectionsHepadnaviridae InfectionsDNA Virus InfectionsVirus DiseasesHepatitis, Viral, HumanHepatitisFlaviviridae InfectionsRNA Virus InfectionsFatty Liver

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 25, 2019

First Posted

February 1, 2019

Study Start

April 11, 2019

Primary Completion

December 29, 2020

Study Completion

January 21, 2021

Last Updated

February 26, 2021

Record last verified: 2021-02

Locations