E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Portopulmonary Hypertension (PoPH) and Hepatopulmonary Syndrome HPS are present in a considerable number of patients with compensated cirrhosis. Treatment of PoPH with ambrisentan is well tolerated and improves hemodynamics as well as symptoms and physical capacity. |
|
E.1.1.1 | Medical condition in easily understood language |
Therapy of portopulmonary hypertension (high blood pressure in the pulmonary circulation) with ambrisentan (medicinal product for the therapy of portopulmonary hypertension). |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067281 |
E.1.2 | Term | Portopulmonary hypertension |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the prevalence of PoPH and HPS in patients with portal hypertension seen in a referral center, using sensitive screening tools. |
|
E.2.2 | Secondary objectives of the trial |
2. To relate PoPH with gender, etiology of cirrhosis, and the degree of liver dysfunction as estimated by the Child-Pugh score or the model for end-stage liver disease (MELD) 3. To relate PVR with portal hemodynamic parameters and circulating vasoactive mediators such as ADMA 4. To evaluate the efficacy and safety of treatment with the endothelin receptor antagonist ambrisentan in patients with clinically significant PoPH
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Adult patients with portal hypertension, age >18 years Cirrhosis of any etiology; Child-Pugh class A, B, or C Noncirrhotic portal hypertension (e.g. chronic portal vein thrombosis) Signed Informed consent
|
|
E.4 | Principal exclusion criteria |
- Presence of other causes for PAH - History of pulmonary embolism or myocardial infarction within 6 months before study start -Presence of hepatocellular carcinoma -Liver transplantation -HIV infection -Severe obstructive or restrictive pulmonary disease (predicted FEV1 or VC <65%, respectively) -Severe dilated cardiomyopathy (EF <50%) -Pregnancy -Esophageal variceal hemorrhage within the last 6 weeks -Refractory ascites -Hepatorenal syndrome -Persistent hepatic encephalopathy > grade 1
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Resting Pulmonary Vascular Resistance (PVR)
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
At baseline and 6 months after the start of treatment |
|
E.5.2 | Secondary end point(s) |
Secondary endpoints include mPAP, HVPG, 6-min walk distance, peak VO2, VAS, SF-36, CAMPHOR score, safety (including detailed liver function tests) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
At baseline, 6 and 12 months after the start of treatment, respectively. For details please refer to the protocoll. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
please refer to the protocoll |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |