CirrhosisPhase 2NCT03827200
A Study Evaluating the Utility of Ambrisentan in Lowering Portal Pressure in Patients With Liver Cirrhosis
A Phase 2 study testing Ambrisentan in people with Cirrhosis and Portal Hypertension, run by Noorik Biopharmaceuticals AG at 6 sites in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cirrhosis, Portal Hypertension, Ascites
- What is being tested?
- Ambrisentan
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 6 sitesSpain
- Study dates
- 11 Apr 2019to 21 Jan 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
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- 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
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Spain6 sites
Hospital Clinic Barcelona
Barcelona, Catalonia, 08036
Vall d'Hebron University Hospital
Barcelona, 08035
Hospital de la Santa Creu i Sant Pau
Barcelona, 08041
Hospital Universitario Gregorio Marañón
Madrid, 28007
Hospital Universitario Ramón y Cajal
Madrid, 28034
Hospital Universitario Puerta de Hierro-Majadahonda
Majadahonda, Madrid, 28222
About this study
Official title: A Phase II, Single-arm, Open-label Study to Characterise the Effect on Portal Pressure, the Effect on Renal Function and the Pharmacokinetic Profile of N-003 in Patients With Decompensated Cirrhosis
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.
- Conditions
- Cirrhosis, Portal Hypertension, Ascites
- Being tested
- Ambrisentan
- Keywords
- Cirrhosis, Portal Hypertension, Ambrisentan, N-003, Hepatic Vein Pressure Gradient, HVPG, Refractory Ascites, Varices, Esophageal, Variceal Hemorrhage, Hepatitis B, Hepatitis C, Non-Alcoholic Fatty Liver Disease, Non-alcoholic Steatohepatitis, Ascites
- Medical subject headings
- Fibrosis, Hypertension, Portal, Ascites, Esophageal and Gastric Varices, Hepatitis B, Hepatitis C, Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AmbrisentanDrug
Also called N-003
Ambrisentan will be administered subcutaneously at the Hospital on the days of HVPG deterination and taken orally at home between visits.
| Study group | Role | What they receive |
|---|---|---|
| Ambrisentan | Experimental | Ambrisentan Receives: Drug: Ambrisentan |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 14 Days
Secondary outcomes (10)
Change in 24-hour Urinary Sodium Volume (UNaV)
The change in 24-hour Urinary Sodium Volume (UNaV) will be calculated as the difference in 24-hour UNaV at Baseline and the 24-hour UNaV at Day 1 (after the first study drug administration).
Urinary sodium volume collected in the 24 hours of baseline will be compared to the Urinary sodium volume collected in the 24 hours after the first dose of the drug. Collection of urine will be ongoing for 48 hours in total.
Measured: 48 hours
Change in weight
The change in weight will be calculated as the difference in weight at baseline and weight recorded throughout the study
Measured: 28 days
Change in abdominal girth
The change in abdominal girth will be calculated as the difference in abdominal girth at baseline and abdominal girth recorded throughout the study
Measured: 28 days
Change in Model of End-Stage Liver Disease (MELD) score
The change in MELD score will be calculated as the difference in MELD score at baseline and the MELD scores recorded throughout the study.
The MELD score is calculated according to the following formula:
MELD = 3.78×ln[serum bilirubin (mg/dL)] + 11.2×ln[INR] + 9.57×ln[serum creatinine (mg/dL)] + 6.43
The MELD score provides an indication of the anticipated mortality observed in previous studies when subjects were followed for 3-months, according to the following ranges:
71.3% mortality if score is 40 points or more
52.6% mortality if score between 30-39 points
19.6% mortality if score between 20-29 points
6.0% mortality if score between 10-19 points
1.9% mortality if score 9 points or less
The MELD score will be calculated at each visit during a 28 day period.
Measured: 28 days
Change in Child-Pugh score
The change in Child-Pugh score will be calculated as the difference in Child-Pugh score at baseline and the Child-Pugh scores recorded throughout the study
The Child-Pugh score provides information on the prognosis of a patient based on 5 clinical parameters which are individually graded. These parameters include laboratory values and other clinical information from the patient, such as the presence of ascites or hepatic encephalopathy. A lower score signifies a better chance and a higher score indicates a worse chance of survival at one year. Once the score is calculated it is further subclassified into three stages, depending on the score:
Child A - the score is between 5 and 6. The survival rate is 100%
Child B - the score is between 7 and 9. The survival rate is 80%
Child C - the score is between 10 and 15. The survival rate is 45%
Measured: 28 days
Change in Cardiac Output
The change in Cardiac Output will be calculated as the difference in Cardiac Output at baseline and the Cardiac Output recorded at Day 14
Measured: 14 days
Change in Cardiac Index
The change in Cardiac Index will be calculated as the difference in Cardiac Index at baseline and the Cardiac Index recorded at Day 14
Measured: 14 days
Change in Pulmonary Capillary Wedge Pressure
The change in Pulmonary Capillary Wedge Pressure will be calculated as the difference in Pulmonary Capillary Wedge Pressure at baseline and the Pulmonary Capillary Wedge Pressure recorded at Day 14
Measured: 14 days
Change in Pulmonary Arterial Pressure
The change in Pulmonary Arterial Pressure will be calculated as the difference in Pulmonary Arterial Pressure at baseline and the Pulmonary Arterial Pressure recorded at Day 14
Measured: 14 days
Change in Central Venous Pressure
The change in Central Venous Pressure will be calculated as the difference in Central Venous Pressure at baseline and the Central Venous Pressure recorded at Day 14
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2019
- Study start11 Apr 2019
- Primary completion29 Dec 2020
- Study completion21 Jan 2021
Why it stopped: Lack of recruitment, result of COVID-19 pandemic
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CirrhosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Noorik Biopharmaceuticals AG
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03827200
- Sponsor's protocol ID
- N-003-CRD003
- Other IDs
- 2018-002088-25, 2018
- Status last verified
- Feb 2021
- First submitted
- 25 Jan 2019
- Last updated
- 26 Feb 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Single-arm, Open-label Study to Characterise the Effect on Portal Pressure, the Effect on Renal Function and the Pharmacokinetic Profile of N-003 in Patients With Decompensated Cirrhosis
- ClinicalTrials.gov ID
- NCT03827200
- Acronym / sponsor ID
- N-003-CRD003
- Conditions
- Cirrhosis, Portal Hypertension, Ascites
- Keywords
- Cirrhosis, Portal Hypertension, Ambrisentan, N-003, Hepatic Vein Pressure Gradient, HVPG, Refractory Ascites, Varices, Esophageal
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of recruitment, result of COVID-19 pandemic
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Noorik Biopharmaceuticals AGIndustry (pharma, biotech, devices)
- Study start
- 11 Apr 2019 (actual)
- Primary completion
- 29 Dec 2020 (actual)
- Study completion
- 21 Jan 2021 (actual)
- First posted
- 1 Feb 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ambrisentan | Experimental | Drug: AmbrisentanAmbrisentan |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (38 listed)
- Age <18 years of age
- Any of the following laboratory findings at the time of screening
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AmbrisentanAlso: N-003Ambrisentan will be administered subcutaneously at the Hospital on the days of HVPG deterination and taken orally at home between visits. | Drug | Ambrisentan |
Primary outcome
Mean change in Hepatic Vein Pressure Gradient (HVPG) from Baseline to Day 14
Time frame: 14 Days
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
10 secondary outcomes
Change in 24-hour Urinary Sodium Volume (UNaV)
Time frame: 48 hours
Change in weight
Time frame: 28 days
Change in abdominal girth
Time frame: 28 days
Change in Model of End-Stage Liver Disease (MELD) score
Time frame: 28 days
Change in Child-Pugh score
Time frame: 28 days
Change in Cardiac Output
Time frame: 14 days
Change in Cardiac Index
Time frame: 14 days
Change in Pulmonary Capillary Wedge Pressure
Time frame: 14 days
Change in Pulmonary Arterial Pressure
Time frame: 14 days
Change in Central Venous Pressure
Time frame: 14 days
Results and safety
The study was stopped early (reason given: Lack of recruitment, result of COVID-19 pandemic). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Feb 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ambrisentan in people with Cirrhosis and Portal Hypertension, run by Noorik Biopharmaceuticals AG at 6 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 38 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 26 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Lack of recruitment, result of COVID-19 pandemic). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean change in Hepatic Vein Pressure Gradient (HVPG) from Baseline to Day 14 (time frame: 14 Days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Feb 2021.