NCT02382016: PORTICO

PORtopulmonary Hypertension Treatment wIth maCitentan - a randOmized Clinical Trial

Completed Phase 4 Results posted Last updated 30 March 2025

What this trial tests

Phase 4 trial testing Macitentan in Portopulmonary Hypertension in 85 participants. Completed in 31 October 2018.

Timeline

23 June 2015

Primary endpoint
25 October 2017

31 October 2018

Quick facts

Lead sponsor	Actelion
Phase	Phase 4
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	85
Start date	23 June 2015
Primary completion	25 October 2017
Estimated completion	31 October 2018
Sites	52 locations across France, United Kingdom, Germany, Spain, United States, Brazil, Czechia

Drugs / interventions tested

• Macitentan (MACITENTAN) — full drug profile →
• Placebo

Conditions studied

• Portopulmonary Hypertension — all drugs for Portopulmonary Hypertension →

Sponsor

Actelion — full company profile →

Who can join

18 and older, any sex, with Portopulmonary Hypertension. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Relative Change From Baseline to Week 12 in Pulmonary Vascular Resistance (PVR). Primary · 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.

Group	Value	95% CI
Macitentan 10 mg	0.63	0.58 – 0.67
Placebo	0.98	0.91 – 1.05

Change From Baseline to Week 12 in 6-minute Walk Distance (6MWD) Secondary · From enrollment/baseline to Week 12 in the DB treatment period

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.

6MWD at baseline

Group	Value	95% CI
Macitentan 10 mg	385.8	± 99.97
Placebo	383.2	± 108.90

6MWD at Week 12

Group	Value	95% CI
Macitentan 10 mg	392.2	± 98.46
Placebo	380.8	± 114.98

Change of 6MWD from baseline to Week 12

Group	Value	95% CI
Macitentan 10 mg	6.4	± 65.74
Placebo	-2.4	± 43.65

Change From Baseline to Week 12 in WHO Functional Class (FC) Secondary · From enrollment/baseline to Week 12 in the DB treatment period

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 inabilit

WHO FC I at baseline

Group	Value	95% CI
Macitentan 10 mg	1
Placebo	1

WHO FC II at baseline

Group	Value	95% CI
Macitentan 10 mg	27
Placebo	23

WHO FC III at baseline

Group	Value	95% CI
Macitentan 10 mg	15
Placebo	18

WHO FC IV at baseline

Group	Value	95% CI
Macitentan 10 mg	0
Placebo	0

WHO FC I at Week 12

Group	Value	95% CI
Macitentan 10 mg	3
Placebo	4

WHO FC II at Week 12

Group	Value	95% CI
Macitentan 10 mg	27
Placebo	23

WHO FC III at Week 12

Group	Value	95% CI
Macitentan 10 mg	13
Placebo	15

WHO FC IV at Week 12

Group	Value	95% CI
Macitentan 10 mg	0
Placebo	0

Change From Baseline to Week 12 in the Biomarker N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) Secondary · From enrollment/baseline to Week 12 in the DB treatment period

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.

Group	Value	95% CI
Macitentan 10 mg	0.86	0.67 – 1.11
Placebo	1.04	0.81 – 1.34

Change From Baseline to Week 12 in Mean Right Atrial Pressure (mRAP) Secondary · From enrollment/baseline to Week 12 in the DB treatment period

mRAP is the mean blood pressure in the right atrium of the heart.

mRAP at baseline

Group	Value	95% CI
Macitentan 10 mg	7.3	± 3.74
Placebo	6.7	± 3.60

mRAP at Week 12

Group	Value	95% CI
Macitentan 10 mg	9.0	± 5.32
Placebo	7.0	± 2.93

Change in mRAP from baseline to Week 12

Group	Value	95% CI
Macitentan 10 mg	1.6	± 5.55
Placebo	0.3	± 3.29

Change From Baseline to Week 12 in Mean Pulmonary Artery Pressure (mPAP) Secondary · From enrollment/baseline to Week 12 in the DB treatment period

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.

mPAP at baseline

Group	Value	95% CI
Macitentan 10 mg	46.4	± 7.89
Placebo	43.8	± 8.52

mPAP at Week 12

Group	Value	95% CI
Macitentan 10 mg	40.0	± 7.61
Placebo	44.2	± 8.26

Change in mPAP at Week 12

Group	Value	95% CI
Macitentan 10 mg	-6.4	± 4.94
Placebo	0.4	± 7.04

Change From Baseline to Week 12 in Cardiac Index Secondary · From enrollment/baseline to Week 12 in the DB treatment period

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).

Cardiac index at baseline

Group	Value	95% CI
Macitentan 10 mg	3.1	± 0.83
Placebo	2.9	± 0.76

Cardiac index at Week 12

Group	Value	95% CI
Macitentan 10 mg	3.7	± 1.04
Placebo	3.0	± 0.82

Change in cardiac index at Week 12

Group	Value	95% CI
Macitentan 10 mg	0.6	± 0.8
Placebo	0.1	± 0.6

Change From Baseline to Week 12 in Total Pulmonary Resistance (TPR) Secondary · From enrollment/baseline to Week 12 in the DB treatment period

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.

TPR at baseline

Group	Value	95% CI
Macitentan 10 mg	689.3	± 228.59
Placebo	671.5	± 199.73

TPR at Week 12

Group	Value	95% CI
Macitentan 10 mg	489.4	± 157.13
Placebo	653.1	± 197.88

Change in TPR from baseline to Week 12

Group	Value	95% CI
Macitentan 10 mg	-199.8	± 163.06
Placebo	-18.3	± 135.28

Change From Baseline to Week 12 in Mixed Venous Oxygen Saturation (SVO2) Secondary · From enrollment/baseline to Week 12 in the DB treatment period

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.

SVO2 at baseline

Group	Value	95% CI
Macitentan 10 mg	69.2	± 9.87
Placebo	69.9	± 5.34

SVO2 at Week 12

Group	Value	95% CI
Macitentan 10 mg	70.3	± 7.07
Placebo	70.7	± 8.58

Change in SVO2 from baseline to Week 12

Group	Value	95% CI
Macitentan 10 mg	1.1	± 6.70
Placebo	0.8	± 7.81

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 3.4 years. Reporting threshold: 1%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Double-Blind (DB) Period: Macitentan 10 mg

Serious: 9/43 (21%)

Deaths: 0/43

DB Period: Placebo

Serious: 6/42 (14%)

Deaths: 0/42

Open-Label (OL) Period: Macitentan 10 mg

Serious: 18/80 (23%)

Deaths: 4/80

OL Extension Period: Macitentan 10 mg

Serious: 11/33 (33%)

Deaths: 2/33

Serious adverse events (57 terms)

Reaction	System	Double-Blind (DB) Period: …	DB Period: Placebo	Open-Label (OL) Period: Ma…	OL Extension Period: Macit…
Anaemia	Blood and lymphatic system disorders	—	—	—	—
Right Ventricular Failure	Cardiac disorders	—	—	—	—
Melaena	Gastrointestinal disorders	—	—	—	—
Hepatocellular Carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—
Hepatic Encephalopathy	Nervous system disorders	—	—	—	—
Iron Deficiency Anaemia	Blood and lymphatic system disorders	—	—	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—	—
Atrial Fibrillation	Cardiac disorders	—	—	—	—
Left Ventricular Failure	Cardiac disorders	—	—	—	—
Tinnitus	Ear and labyrinth disorders	—	—	—	—
Abdominal Pain	Gastrointestinal disorders	—	—	—	—
Ascites	Gastrointestinal disorders	—	—	—	—
Duodenal Vascular Ectasia	Gastrointestinal disorders	—	—	—	—
Gastrointestinal Angiodysplasia	Gastrointestinal disorders	—	—	—	—
Gastrointestinal Haemorrhage	Gastrointestinal disorders	—	—	—	—
Ileus	Gastrointestinal disorders	—	—	—	—
Intestinal Obstruction	Gastrointestinal disorders	—	—	—	—
Portal Hypertensive Gastropathy	Gastrointestinal disorders	—	—	—	—
Death	General disorders	—	—	—	—
Localised Oedema	General disorders	—	—	—	—
Oedema Peripheral	General disorders	—	—	—	—
Hepatic Failure	Hepatobiliary disorders	—	—	—	—
Hypersensitivity	Immune system disorders	—	—	—	—
Bronchitis	Infections and infestations	—	—	—	—
Escherichia Pyelonephritis	Infections and infestations	—	—	—	—

Other adverse events (216 terms — click to expand)

Reaction	System	Double-Blind (DB) Period: …	DB Period: Placebo	Open-Label (OL) Period: Ma…	OL Extension Period: Macit…
Oedema Peripheral	General disorders	—	—	—	—
Bronchitis	Infections and infestations	—	—	—	—
Headache	Nervous system disorders	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—
Rhinitis	Infections and infestations	—	—	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—	—	—
Pain in Extremity	Musculoskeletal and connective tissue disorders	—	—	—	—
Muscle Spasms	Musculoskeletal and connective tissue disorders	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—
Insomnia	Psychiatric disorders	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—
Asthenia	General disorders	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—
Influenza Like Illness	General disorders	—	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—	—
Haemoglobin Decreased	Investigations	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Dyspnoea Exertional	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Oropharyngeal Pain	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—	—	—
Hypotension	Vascular disorders	—	—	—	—
Palpitations	Cardiac disorders	—	—	—	—
Tachycardia	Cardiac disorders	—	—	—	—
Dry Eye	Eye disorders	—	—	—	—
Abdominal Pain	Gastrointestinal disorders	—	—	—	—
Ascites	Gastrointestinal disorders	—	—	—	—
Dry Mouth	Gastrointestinal disorders	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—
Fatigue	General disorders	—	—	—	—
Peripheral Swelling	General disorders	—	—	—	—
Sinusitis	Infections and infestations	—	—	—	—
Urinary Tract Infection	Infections and infestations	—	—	—	—
Fall	Injury, poisoning and procedural complications	—	—	—	—
Foot Fracture	Injury, poisoning and procedural complications	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—
Back Pain	Musculoskeletal and connective tissue disorders	—	—	—	—
Musculoskeletal Chest Pain	Musculoskeletal and connective tissue disorders	—	—	—	—
Osteoarthritis	Musculoskeletal and connective tissue disorders	—	—	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—	—	—

Most-reported serious reactions: Anaemia, Right Ventricular Failure, Melaena, Hepatocellular Carcinoma, Hepatic Encephalopathy, Iron Deficiency Anaemia, Thrombocytopenia, Atrial Fibrillation.

Data from ClinicalTrials.gov NCT02382016 adverse events section.

Sponsor's own description

24-week study to evaluate the efficacy and safety of macitentan for the treatment of portopulmonary hypertension.

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

1. Macitentan for the treatment of portopulmonary hypertension (PORTICO): a multicentre, randomised, double-blind, placebo-controlled, phase 4 trial.
   Sitbon O, Bosch J, Cottreel E, Csonka D, et al · · 2019 · cited 117× · PMID 31178422 · DOI 10.1016/s2213-2600(19)30091-8
2. Treatment Barriers in Portopulmonary Hypertension.
   AbuHalimeh B, Krowka MJ, Tonelli AR. · · 2019 · cited 28× · PMID 30063259 · DOI 10.1002/hep.30197
3. Pulmonary manifestations of chronic liver disease: a comprehensive review.
   Soulaidopoulos S, Goulis I, Cholongitas E. · · 2020 · cited 23× · PMID 32382226 · DOI 10.20524/aog.2020.0474
4. Macitentan Improves Risk Categorization for Liver Transplant Mortality in Patients With Portopulmonary Hypertension: A PORTICO Study Post Hoc Analysis.
   Krowka M, Cottreel E, Hoeper MM, Kim NH, et al · · 2020 · cited 17× · PMID 32150762 · DOI 10.1002/lt.25747
5. Treatment of pulmonary arterial hypertension with the dual endothelin receptor antagonist macitentan: clinical evidence and experience.
   Belge C, Delcroix M. · · 2019 · cited 16× · PMID 30736726 · DOI 10.1177/1753466618823440