Portopulmonary HypertensionPhase 4PORTICONCT02382016
PORtopulmonary Hypertension Treatment wIth maCitentan - a randOmized Clinical Trial
A Phase 4 study testing Macitentan in people with Portopulmonary Hypertension, run by Actelion at 52 sites in 7 countries.
Trial summary
24-week study to evaluate the efficacy and safety of macitentan for the treatment of portopulmonary hypertension. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Portopulmonary Hypertension
- What is being tested?
- Macitentan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 85 participants
- Where
- 52 sitesin 7 countries
- Study dates
- 23 Jun 2015to 31 Oct 2018
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
Main Inclusion Criteria:
- Male or female of at least 18 years of age
- Confirmed diagnosis of portopulmonary hypertension
Main Exclusion Criteria:
- Severe hepatic impairment
- Severe obstructive or restrictive lung disease
- Pulmonary veno-occlusive disease
- Systolic blood pressure (SBP) < 90 mmHg at Screening
- ALT/AST >= 3 x ULN
- Bilirubin >= 3 mg/dL at Screening
- Any known factor or disease that might interfere with treatment compliance, study conduct, or interpretation of results
Trial locations and contacts
52 sites in 7 countries.
52 sites in 7 countries
United States29 sites
University of New Mexico Health Science Center
Albuquerque, New Mexico, 87131-0001
Emory Healthcare
Atlanta, Georgia, 30322
University of Colorado Health Sciences Center Aurora
Aurora, Colorado, 80045
Piedmont Healthcare
Austell, Georgia, 30106
Boston University
Boston, Massachusetts, 02118
Northwestern University
Chicago, Illinois, 60611
University of Cincinnati
Cincinnati, Ohio, 45267
Cleveland Clinic - Department of Cardiovascular Medicine
Cleveland, Ohio, 44195
Baylor University Medical Center
Dallas, Texas, 75226
University of Texas Southwestern Medical Center Division of NeuroCritical Care 75390-8550
Dallas, Texas, 75390-8550
Henry Ford Hospital
Detroit, Michigan, 48202
University of Florida - Divison of Pulmonary Critical Care & Sleep
Gainesville, Florida, 32610
Methodist Hospital
Houston, Texas, 77030
Indiana University
Indianapolis, Indiana, 46202
University of Florida College of Medicine
Jacksonville, Florida, 32209
Mayo Clinic Florida - Pulmonary Dept.
Jacksonville, Florida, 32224
UCSD
La Jolla, California, 92093
David Geffen School of Medicine, UCLA
Los Angeles, California, 90025-1690
Keck School of Medicine
Los Angeles, California, 90033
Kentuckiana Pulmonary Associates
Louisville, Kentucky, 40202
University of Wisconsin-Madison
Madison, Wisconsin, 53705-2281
University of Miami
Miami, Florida, 33136
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Mayo Clinic -Clinical Studies Unit
Phoenix, Arizona, 85054
UPMC Montefiore
Pittsburgh, Pennsylvania, 15213
Mayo Clinic
Rochester, Minnesota, 55905
Methodist Hospital
San Antonio, Texas, 78229
UCSF
San Francisco, California, 91413-2204
South Miami Hospital
South Miami, Florida, 33143
France9 sites
CHRU Hôpital Cavale Blanche Brest
Brest, Brittany Region, 29609
CHU Côte de Nacre, Service de Pneumologie
Caen, 14033
CHRU de Grenoble, Hôpital Albert Michallon
Grenoble, Auvergne-Rhône-Alpes, 38043
Hôpital cardiologique, Service de cardiologie 59037 Lille Cedex"
Lille, 59037
Hôpital Cardiologique et Pneumologique Louis Pradel 69677 Bron cedex"
Lyon, 69677
Hôpital Kremlin Bicêtre Service de Pneumologie
Paris, 94275
Hôpital Pontchaillou - CHU Rennes Service de Cardiologie et des Maladies Vasculaires Rennes Cedex 9 35033"
Rennes, 35033
CHU Rouen
Rouen, 76031
CHU Toulouse - Hôpital Larrey Hôpital de Jour et Semaine
Toulouse, 31059
Germany5 sites
Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden
Dresden, 01307
Universitätsklinikum Giessen und Marburg GmbH Justus-Liebig Universität Giessen 35392
Giessen, 35392
Medizinische Hochschule Hannover, Abteilung Pneumologie
Hanover, 30625
Thoraxklinik des Universitätsklinikums Heidelberg Zentrum für pulmonale Hypertonie Studienkoordination
Heidelberg, 69126
Universitätsklinikum Leipzig, Department Innere Medizin, Abteilung Pneumologie
Leipzig, 04103
United Kingdom3 sites
NHS Greater Glasgow and Clyde Trust
Glasgow, Scotland, G11 6NT
The Royal Free Hospital/ Cardiology Department
London, NW3 2QG
Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital
Sheffield, S10 2RX
Brazil2 sites
Servico de Hipertensao Pulmonar - Complexo Hospitalar Santa Casa Irmandade Santa de Misericordia de Porto Alegre
Porto Alegre, 92020-090
Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HC-FMUSP)
São Paulo, 05403-000
Czechia2 sites
Lékařská fakulta a Všeobecná fakultní nemocnice v Praze, II. Interní klinika kardiologie a angiologie U
Prague, 128 08
IKEM (Institut klinické a experimentální medicíny, Institute for Clinical and Experimental Medicine)
Prague, 140 21
Spain2 sites
Hospital Clinico i Provincial Servicio de Neumología
Barcelona, 08036
Hospital Universitario12 Octubre
Madrid, 28041
About this study
Official title: A Randomized, Double-blind, Placebo-controlled, Prospective, Multicenter, Parallel Group Study to Assess the Safety and Efficacy of Macitentan in Patients With Portopulmonary Hypertension
24-week study to evaluate the efficacy and safety of macitentan for the treatment of portopulmonary hypertension.
- Conditions
- Portopulmonary Hypertension
- Being tested
- Macitentan, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MacitentanDrug
Also called ACT-064992
Macitentan film-coated tablet 10 mg once daily.
PlaceboOther
Matching placebo tablet once daily.
| Study group | Role | What they receive |
|---|---|---|
| Investigational treatment | Experimental | Macitentan film-coated tablet 10 mg once daily. Receives: Drug: Macitentan |
| Placebo | Placebo comparator | Matching placebo tablet once daily. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Relative Change From Baseline to Week 12 in Pulmonary Vascular Resistance (PVR).
The relative change from baseline to Week 12 in PVR is expressed as a ratio of Week 12 to baseline PVR.
Measured: From enrollment/baseline to Week 12 in the Double Blind (DB) treatment period
Secondary outcomes (8)
Change From Baseline to Week 12 in 6-minute Walk Distance (6MWD)
The purpose of the six minute walk is to test exercise tolerance and capacity. The test measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes.
Measured: From enrollment/baseline to Week 12 in the DB treatment period
Change From Baseline to Week 12 in WHO Functional Class (FC)
Changes from baseline to Week 12 in WHO FC were dichotomized as worsening (i.e., change > 0) versus no change or improvement (i.e., change ≤ 0). Class I: no symptoms with exercise or at rest. No limitation of activity. Class II: No symptoms at rest but slight limitation with ordinary activities causing symptoms (e.g. short of breath with climbing a flight of stairs, grocery shopping, or making the bed). Class III: may not have symptoms at rest but activities greatly limited by shortness of breath, fatigue, or near fainting. Class IV: symptoms at rest (e.g. dyspnea and/or fatigue) and inability to carry out any physical activity without symptoms. Patients in class IV manifest signs of right heart failure.
Measured: From enrollment/baseline to Week 12 in the DB treatment period
Change From Baseline to Week 12 in the Biomarker N-terminal Pro B-type Natriuretic Peptide (NT-proBNP)
NT-proBNP functions as a strong indicator of prognosis in patients with pulmonary hypertension (PH). The relative change from baseline to Week 12 in NT-proBNP is expressed as a ratio of Week 12 to baseline NT-proBNP.
Measured: From enrollment/baseline to Week 12 in the DB treatment period
Change From Baseline to Week 12 in Mean Right Atrial Pressure (mRAP)
mRAP is the mean blood pressure in the right atrium of the heart.
Measured: From enrollment/baseline to Week 12 in the DB treatment period
Change From Baseline to Week 12 in Mean Pulmonary Artery Pressure (mPAP)
mPAP is the mean blood pressure inside the pulmonary artery which moves the blood from the heart to the lungs. Monitoring of mPAP can detect small changes in the function of the heart.
Measured: From enrollment/baseline to Week 12 in the DB treatment period
Change From Baseline to Week 12 in Cardiac Index
The cardiac index is an assessment of the function of the heart and relates the cardiac output to the patient's body size (the patient's body surface area).
Measured: From enrollment/baseline to Week 12 in the DB treatment period
Change From Baseline to Week 12 in Total Pulmonary Resistance (TPR)
TPR is the resistance the pulmonary circulation that must be overcome in order for the blood flow to occur. It takes into account the blood pressure in the pulmonary arteries and the cardiac output. It is an important measurement to monitor the function of the pulmonary circulation and detect disease progression or improvement.
Measured: From enrollment/baseline to Week 12 in the DB treatment period
Change From Baseline to Week 12 in Mixed Venous Oxygen Saturation (SVO2)
SVO2 help assess tissue oxygen delivery. It describes the percentage of oxygen bound to hemoglobin in the blood which returns to the heart. This reflects the amount of residual oxygen in the blood after oxygen extraction by the tissues throughout the body.
Measured: From enrollment/baseline to Week 12 in the DB treatment period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2015 (estimated)
- Study start23 Jun 2015
- Primary completion25 Oct 2017
- Study completion31 Oct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Portopulmonary HypertensionStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 85 participants (actual)
Sponsor and investigators
- Lead sponsor
- Actelion
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Loïc Perchenet, PhD, Study director, Actelion
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02382016
- Sponsor's protocol ID
- AC-055-404
- Acronym
- PORTICO
- Status last verified
- Mar 2025
- First submitted
- 3 Mar 2015
- Last updated
- 30 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Raevens S, Fallon MB. PORTICO: First Randomized Controlled Trial of Vasomodulator Therapy in Portopulmonary Hypertension. Hepatology. 2020 May;71(5):1870-1872. doi: 10.1002/hep.31166. No abstract available.
PubMed 32031690Sitbon O, Bosch J, Cottreel E, Csonka D, de Groote P, Hoeper MM, Kim NH, Martin N, Savale L, Krowka M. Macitentan for the treatment of portopulmonary hypertension (PORTICO): a multicentre, randomised, double-blind, placebo-controlled, phase 4 trial. Lancet Respir Med. 2019 Jul;7(7):594-604. doi: 10.1016/S2213-2600(19)30091-8. Epub 2019 Jun 6.
PubMed 31178422
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Placebo-controlled, Prospective, Multicenter, Parallel Group Study to Assess the Safety and Efficacy of Macitentan in Patients With Portopulmonary Hypertension
- ClinicalTrials.gov ID
- NCT02382016
- Acronym / sponsor ID
- PORTICO / AC-055-404
- Conditions
- Portopulmonary Hypertension
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 85 participants (actual)
- Lead sponsor
- ActelionIndustry (pharma, biotech, devices)
- Study start
- 23 Jun 2015 (actual)
- Primary completion
- 25 Oct 2017 (actual)
- Study completion
- 31 Oct 2018 (actual)
- First posted
- 6 Mar 2015 (estimated)
- Results
- Posted 23 Nov 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
24-week study to evaluate the efficacy and safety of macitentan for the treatment of portopulmonary hypertension.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Investigational treatment | Experimental | Drug: MacitentanMacitentan film-coated tablet 10 mg once daily. |
| Placebo | Placebo comparator | Other: PlaceboMatching placebo tablet once daily. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| MacitentanAlso: ACT-064992Macitentan film-coated tablet 10 mg once daily. | Drug | Investigational treatment |
| PlaceboMatching placebo tablet once daily. | Other | Placebo |
Primary outcome
Relative Change From Baseline to Week 12 in Pulmonary Vascular Resistance (PVR).
Time frame: From enrollment/baseline to Week 12 in the Double Blind (DB) treatment period
The relative change from baseline to Week 12 in PVR is expressed as a ratio of Week 12 to baseline PVR.
8 secondary outcomes
Change From Baseline to Week 12 in 6-minute Walk Distance (6MWD)
Time frame: From enrollment/baseline to Week 12 in the DB treatment period
Change From Baseline to Week 12 in WHO Functional Class (FC)
Time frame: From enrollment/baseline to Week 12 in the DB treatment period
Change From Baseline to Week 12 in the Biomarker N-terminal Pro B-type Natriuretic Peptide (NT-proBNP)
Time frame: From enrollment/baseline to Week 12 in the DB treatment period
Change From Baseline to Week 12 in Mean Right Atrial Pressure (mRAP)
Time frame: From enrollment/baseline to Week 12 in the DB treatment period
Change From Baseline to Week 12 in Mean Pulmonary Artery Pressure (mPAP)
Time frame: From enrollment/baseline to Week 12 in the DB treatment period
Change From Baseline to Week 12 in Cardiac Index
Time frame: From enrollment/baseline to Week 12 in the DB treatment period
Change From Baseline to Week 12 in Total Pulmonary Resistance (TPR)
Time frame: From enrollment/baseline to Week 12 in the DB treatment period
Change From Baseline to Week 12 in Mixed Venous Oxygen Saturation (SVO2)
Time frame: From enrollment/baseline to Week 12 in the DB treatment period
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32031690Raevens S, Fallon MB. PORTICO: First Randomized Controlled Trial of Vasomodulator Therapy in Portopulmonary Hypertension. Hepatology. 2020 May;71(5):1870-1872. doi: 10.1002/hep.31166. No abstract available.
- Derived from this study: PubMed 31178422Sitbon O, Bosch J, Cottreel E, Csonka D, de Groote P, Hoeper MM, Kim NH, Martin N, Savale L, Krowka M. Macitentan for the treatment of portopulmonary hypertension (PORTICO): a multicentre, randomised, double-blind, placebo-controlled, phase 4 trial. Lancet Respir Med. 2019 Jul;7(7):594-604. doi: 10.1016/S2213-2600(19)30091-8. Epub 2019 Jun 6.
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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.
Loïc Perchenet, PhD study director
Actelion
52 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Macitentan in people with Portopulmonary Hypertension, run by Actelion at 52 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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: finished, as of the sponsor's last update on 30 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 52 sites in United States, France, Germany, United Kingdom, Brazil and 2 more countries. 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. Some participants in this study may receive a placebo. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Nov 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Relative Change From Baseline to Week 12 in Pulmonary Vascular Resistance (PVR). (time frame: From enrollment/baseline to Week 12 in the Double Blind (DB) treatment period). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02382016, which also lists 2 linked publications.
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 30 Mar 2025.