Pulmonary Arterial HypertensionPhase 3TOMORROWNCT02932410
A Study to Assess Whether Macitentan Delays Disease Progression in Children With Pulmonary Arterial Hypertension (PAH)
A Phase 3 study testing Macitentan and Standard-of-care in people with Pulmonary Arterial Hypertension, run by Actelion at 85 sites in 23 countries.
Trial summary
This is a prospective, multicenter, open-label, randomized, controlled, parallel Phase 3 study with an open-label single-arm extension period to evaluate pharmacokinetics (PK), safety and efficacy of macitentan in children with pulmonary arterial hypertension (PAH). Read more about this study
- Who is it for?
- Ages 1 month to 17 years
- Conditions the study is for
- Pulmonary Arterial Hypertension
- What is being tested?
- Macitentan and Standard-of-care
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 165 participants
- Where
- 85 sitesin 23 countries
- Study dates
- 24 Oct 2017to 27 Nov 2025
- Phase
- Phase 3
- 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 1 month to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Signed informed consent by the parent(s) or legally designated representative and assent from developmentally capable children prior to initiation of any study-mandated procedure
- Males or females between greater than or equal to (>=) 1 month and less than (<) 18 years of age
- Participants with body weight >= 3.5 kilograms (kg) at randomization
- Pulmonary arterial hypertension (PAH) diagnosis confirmed by historical RHC (mPAP greater than or equal to [>=] 25 millimeters of mercury [mmHg], and Pulmonary artery wedge pressure [PAWP] less than or equal to [<=] 15 mmHg, and Pulmonary vascular resistance index [PVRi] greater than [>] 3 WU × m2), where in the absence of pulmonary vein obstruction and/or significant lung disease PAWP can be replaced by Left atrium pressure [LAP] or Left ventricular end diastolic pressure [LVEDP] (in absence of mitral stenosis) assessed by heart catheterization
- PAH belonging to the Nice 2013 Updated Classification Group 1 (including participants with Down Syndrome) and of following etiologies: idiopathic PAH; heritable PAH; PAH associated with congenital heart disease (CHD); Drug or toxin induced PAH; PAH associated with HIV; PAH associated with connective tissue diseases (PAH-aCTD); and World health organization (WHO) Functional class I to III
- Females of childbearing potential must have a negative pregnancy test at Screening and at Baseline, and must agree to undertake monthly pregnancy tests, and to use a reliable method of contraception (if sexually active) up to the end of study (EOS)
Who cannot join
- Participants with PAH due to portal hypertension, schistosomiasis, or with pulmonary veno-occlusive disease and/or pulmonary capillary hemangiomatosis, and persistent pulmonary hypertension of the newborn
- Participants with PAH associated with Eisenmenger syndrome, or with moderate to large left-to-right shunts
- Participants receiving a combination of > 2 PAH-specific treatments at randomization.
- Treatment with intravenous (IV) or subcutaneous (SC) prostanoids within 4 weeks before randomization, unless given for vasoreactivity testing
- Hemoglobin or hematocrit <75 percent (%) of the lower limit of normal range
- Serum Aspartate aminotransferase (AST) and/or Alanine aminotransferase (ALT) greater than (>) 3 times the upper limit of normal range
Show all 12Show fewer
- Pregnancy (including family planning) or breastfeeding.
- Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol
- Severe hepatic impairment, for example Child-Pugh Class C
- Clinical signs of hypotension which in the investigator's judgment would preclude initiation of a PAH-specific therapy
- Severe renal insufficiency (estimated creatinine clearance <30 mL/min or serum creatinine >221 micro-moles per liter [micro-mol/L])
- Participants with known diagnosis of bronchopulmonary dysplasia
Trial locations and contacts
85 sites in 23 countries.
85 sites in 23 countries
United States20 sites
Childrens Hospital Colorado
Aurora, Colorado, 80045
Boston Children's Hospital
Boston, Massachusetts, 02115
University of Virginia Health System
Charlottesville, Virginia, 19803
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
University Hospitals Cleveland Medical Center, Rainbow Babies and Childrens Hospital
Cleveland, Ohio, 44106
Nationwide Children's Hospital
Columbus, Ohio, 43205
Detroit Medical Center
Detroit, Michigan, 48201
Duke University Medical Center
Durham, North Carolina, 27710
East Carolina University
Greenville, North Carolina, 27834
Riley Hospital For Children
Indianapolis, Indiana, 46202
Children's Heart Center
Las Vegas, Nevada, 89109
UCLA Children's Heart Center
Los Angeles, California, 90095
Childrens Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
Columbia University Medical Center - PIN
New York, New York, 10032
Phoenix Childrens Hospital
Phoenix, Arizona, 85016
Mayo Clinic - PPDS
Rochester, Minnesota, 55905
Primary Children's Medical Center
Salt Lake City, Utah, 84113
UCSF Medical Center
San Francisco, California, 94143-2202
Montefiore Medical Center
The Bronx, New York, 10467
Children's National Medical Center
Washington D.C., District of Columbia, 20010
Russia7 sites
Research Institute of Complex Cardiovascular Pathology
Kemerovo, 650002
GBUZ Children's Hospital named after Bashlyaeva Z.A. Moscow
Moscow, 125408
Russian National Research Medical University n.a. N.I.Pirogov
Moscow, 125412
Novosibirsk Research Institue of Blood Circulation Pathology n.a. E.N. Meshalkin
Novosibirsk, 630055
Saint Petersburg State Pediatric Medical Academy
Saint Petersburg, 194100
Clinical Hospital №1
Tyumen, 625023
Bashkiria State Medical University
Ufa, 450000
Spain7 sites
Hospital Universitario Vall d'Hebron - PPDS
Barcelona, 08035
C.H. Regional Reina Sofia
Córdoba, 14004
Hospital General Universitario Gregorio Marañon
Madrid, 28009
Hospital Universitario Ramon y Cajal
Madrid, 28034
Hospital Universitario 12 de Octubre
Madrid, 28041
Hospital Universitario La Paz
Madrid, 28046
Hospital Universitari i Politecnic La Fe de Valencia
Valencia, 46026
Mexico5 sites
CICUM San Miguel
Guadalajara, 44160
Operadora de Hospitales Angeles SA de CV Hospital Angeles Lomas
México, 52763
Instituto Nacional de Pediatría
Mexico City, 04530
Instituto Nacional de Cardiologia Dr. Ignacio Chavez
Mexico City, 14080
Unidad de Investigación Clínica En Medicina SC
Monterrey, 64716
China4 sites
Beijing Anzhen Hospital of The Capital University of Medical Sciences
Beijing, 100029
Qingdao Women and Children's Hospital
Qingdao, 26600
Childrens Hospital of Shanghai
Shanghai, 200062
Shanghai Children's Medical Center
Shanghai, 200127
France4 sites
Hôpital de la Timone Enfants
Marseille, 13385
Groupe Hospitalier Necker Enfants Malades
Paris, 75743
Hôpital Haut-Lévêque - Hôpital cardiologique
Pessac, 33604
Hôpital Des Enfants
Toulouse, 31059
Portugal4 sites
Centro Hospitalar de Lisboa Ocidental, EPE - Hospital de Santa Cruz
Carnaxide, 2790-134
Centro Hospitalar E Universitário de Coimbra EPE
Coimbra, 3000-075
Hospital Santa Marta
Lisbon, 1169-024
Centro Hospitalar de Sao Joao EPE
Porto, 4200-319
Vietnam4 sites
Hanoi Heart Hospital
Hanoi, 100000
Hanoi Medical University Hospital
Hanoi, 100000
Children's Hospital 1
Ho Chi Minh City, 700000
Tam Duc Hospital
Ho Chi Minh City, 700000
Australia3 sites
Royal Children's Hospital Melbourne - PIN
Parkville, 3052
Lady Cilento Children's Hospital
South Brisbane, 4101
Children's Hospital at Westmead
Westmead, 2145
Austria3 sites
Medizinische Universität Graz
Graz, 8036
Landes Frauen Und Kinderklinik Linz
Linz, 4020
Medizinische Universitat Wien
Linz, 4020
Israel3 sites
Rambam Medical Center - PPDS
Haifa, 31096
Schneider Children's Medical Center of Israel - PIN
Petah Tikva, 49100
Chaim Sheba Medical Center
Ramat Gan, 52621
Poland3 sites
Szpital Kliniczny im. Karola Jonschera Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu
Poznan, 60-572
Instytut Pomnik - Centrum Zdrowia Dziecka
Warsaw, 04-730
Wojewodzki Szpital Specjalistyczny we Wroclawiu Osrodek Badawczo-Rozwojowy
Wroclaw, 51-124
Ukraine3 sites
MI Dnipropetrovsk Specialized Clin. Med. Center of Mother and Child n.a. prof. M.F. Rudnev of DRC
Dnipro, 49000
Municipal Institution of Health Care Regional Children's Clinical Hospital
Kharkiv, 61093
MI Scientific Practical Medical Center for Children Cardiology and Cardiosurgery of MOH of Ukraine
Kyiv, 04050
Colombia2 sites
Fundacion Santa Fe de Bogota
Bogotá, 220246
Centro Medico Imbanaco de Cali SA
Cali, 760042
Malaysia2 sites
Institut Jantung Negara
Kuala Lumpur, 50400
University Malaya Medical Centre
Kuala Lumpur, 59100
Philippines2 sites
Makati Medical Center
Makati City, 1229
Philippine Heart Center
Quezon City, 0850
South Africa2 sites
University of The Free State
Bloemfontein, 9300
Inkosi Albert Luthuli Central Hospital
Durban, 4001
South Korea2 sites
Seoul National University Hospital
Seoul, 03080
Severance Hospital Yonsei University Health System - PPDS
Seoul, 03722
Brazil1 site
Irmandade Da Santa Casa de Misericórdia de São Paulo
São Paulo, 01221-020
Thailand1 site
Maharaj Nakorn Chiang Mai Chiang Mai University
Chiang Mai, 50200
About this study
Official title: A Multicenter, Open-label, Randomized, Study With Single-arm Extension Period to Assess the Pharmacokinetics, Safety and Efficacy of Macitentan Versus Standard of Care in Children With Pulmonary Arterial Hypertension
This is a prospective, multicenter, open-label, randomized, controlled, parallel Phase 3 study with an open-label single-arm extension period to evaluate pharmacokinetics (PK), safety and efficacy of macitentan in children with pulmonary arterial hypertension (PAH).
- Conditions
- Pulmonary Arterial Hypertension
- Being tested
- Macitentan, Standard-of-care
- Medical subject headings
- Pulmonary Arterial Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MacitentanDrug
Also called ACT-064992
Dispersible tablet; Oral use
Standard-of-careOther
Standard-of-care as per site's clinical practice which may comprise treatment with PAH non-specific treatment and/or up to two PAH-specific medications excluding macitentan and IV/SC prostanoids.
| Study group | Role | What they receive |
|---|---|---|
| Macitentan | Experimental | Macitentan is administered once daily via oral route. Children less than (<) 2 years old (y.o.) will be assigned as a cohort to the macitentan group without randomization. The dose will be adjusted to the participant's age (for those < 2 y.o.) or to the participant's body weight (for those greater than or equal to (>=) 2 y.o.). single-arm extension period (SAEP) will start at end of core period (EOCP) visit and ends at end of study (EOS) visit. Receives: Drug: Macitentan |
| Standard-of-care | Other | Standard-of-care as per site's clinical practice which may comprise treatment with pulmonary arterial hypertension (PAH) non-specific treatment and/or up to two PAH-specific medications excluding macitentan and intravenous/subcutaneous (IV/SC) prostanoids. Receives: Other: Standard-of-care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Participants >=2 Years of Age: Observed Steady-State Trough (Pre-dose) Plasma Concentration of Macitentan and Aprocitentan (Active Metabolite) at Week 12 Based on Body Weight
Observed steady-state trough (pre-dose) plasma concentration of macitentan and aprocitentan (active metabolite) at Week 12 based on body weight were reported. This outcome measure was planned to be analyzed for specified arms only.
Measured: Pre-dose at Week 12
Participants >=2 Years of Age: Observed Steady-State Trough (Pre-dose) Plasma Concentration of Macitentan and Aprocitentan (Active Metabolite) at Week 12 Based on Age Group
Observed steady-state trough (pre-dose) plasma concentration of macitentan and aprocitentan (active metabolite) at Week 12 based on age group were reported. This outcome measure was planned to be analyzed for specified arms only.
Measured: Pre-dose at Week 12
Participants <2 Years of Age: Observed Steady-State Trough (Pre-dose) Plasma Concentration of Macitentan and Aprocitentan (Active Metabolite) at Week 4
Observed steady-state trough (pre-dose) plasma concentration of macitentan and aprocitentan (active metabolite) at Week 4 were reported. This outcome measure was planned to be analyzed for specified arms only.
Measured: Pre-dose at Week 4
Participants From China With >=12 to <18 Years of Age: Observed Steady-State Trough (Pre-dose) Plasma Concentration of Macitentan and Aprocitentan (Active Metabolite) at Week 12
Observed steady-state trough (pre-dose) plasma concentration of macitentan and aprocitentan (active metabolite) at Week 12 were reported.
Measured: Pre-dose at Week 12
Secondary outcomes (19)
Time to the First Clinical Event Committee (CEC)-Confirmed Disease Progression Event
Measured: Baseline (Day 1) up to end of core study period (EOCP; up to 7.08 years)
Time to First CEC-confirmed Hospitalization for PAH
Measured: Baseline (Day 1) up to EOCP (up to 7.08 years)
Time to CEC-confirmed Death Due to PAH
Measured: Baseline (Day 1) up to EOCP (up to 7.08 years)
Time to Death (All Causes)
Measured: Baseline (Day 1) up to 7.26 years
Percentage of Participants With World Health Organization (WHO) Functional Class (FC) I or II Versus III or IV
Measured: At Weeks 12 and 24
Change From Baseline in N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) at Weeks 12 and 24
Measured: Baseline (Day 1), Weeks 12 and 24
Change From Baseline in Mean Daily Time Spent in Moderate to Vigorous Physical Activity as Measured by Accelerometry at Week 48
Measured: Baseline (Day 1), Week 48
Change From Baseline in Body Surface Area (BSA) Normalized Tricuspid Annular Plane Systolic Excursion (TAPSE) Measured by Echocardiography at Week 24
Measured: Baseline (Day 1), Week 24
Change From Baseline in Left Ventricular Eccentricity Index (LVEI) Measured by Echocardiography at Week 24
Measured: Baseline (Day 1), Week 24
Change From Baseline in Quality of Life Measured by Pediatric Quality of Life Inventory Version 4.0 (PedsQL 4.0) Generic Core Scales Short Form (SF-15)
Measured: Baseline (Day 1), Week 24
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Measured: Baseline (Day 1) up to 7.26 years
Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs)
Measured: Baseline (Day 1) up to 7.26 years
Number of Participants With AEs Leading to Premature Discontinuation of Macitentan or Standard of Care (SoC)
Measured: Baseline (Day 1) up to 7.26 years
Number of Participants With AEs of Special Interest
Measured: Baseline (Day 1) up to 7.26 years
Number of Participants With Marked Laboratory Abnormalities
Measured: Baseline (Day 1) up to 7.26 years
Change From Baseline in Selected Laboratory Parameters
Measured: Baseline (Day 1) up to 7.26 years
Change From Baseline in Vital Signs (Blood Pressure, Heart Rate)
Measured: Baseline (Day 1) up to 7.26 years
Change From Baseline in Growth Variable
Measured: Baseline (Day 1) up to 7.26 years
Change From Baseline in Sexual Maturation Measured by Tanner Stage
Measured: Baseline (Day 1) up to 7.26 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2016 (estimated)
- Study start24 Oct 2017
- Primary completion28 Aug 2024
- Study completion27 Nov 2025
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 (1)Papers the sponsor has linked to this study.
- Other trials for Pulmonary Arterial 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 165 participants (actual)
Sponsor and investigators
- Lead sponsor
- Actelion
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02932410
- Sponsor's protocol ID
- AC-055-312
- Acronym
- TOMORROW
- Status last verified
- Mar 2026
- First submitted
- 12 Oct 2016
- Last updated
- 13 Mar 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Berger RMF, Dunbar Ivy D, Borissoff JI, Cerovic S, Csonka D, Remenova T, Richard D, Villeneuve M, Beghetti M. Macitentan in Pediatric Pulmonary Arterial Hypertension (TOMORROW): A Randomized Clinical Trial. J Pediatr. 2026 Jun;293:115057. doi: 10.1016/j.jpeds.2026.115057. Epub 2026 Mar 6.
PubMed 41796854
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Open-label, Randomized, Study With Single-arm Extension Period to Assess the Pharmacokinetics, Safety and Efficacy of Macitentan Versus Standard of Care in Children With Pulmonary Arterial Hypertension
- ClinicalTrials.gov ID
- NCT02932410
- Acronym / sponsor ID
- TOMORROW / AC-055-312
- Conditions
- Pulmonary Arterial Hypertension
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 165 participants (actual)
- Lead sponsor
- ActelionIndustry (pharma, biotech, devices)
- Study start
- 24 Oct 2017 (actual)
- Primary completion
- 28 Aug 2024 (actual)
- Study completion
- 27 Nov 2025 (actual)
- First posted
- 13 Oct 2016 (estimated)
- Results
- Posted 12 Sep 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a prospective, multicenter, open-label, randomized, controlled, parallel Phase 3 study with an open-label single-arm extension period to evaluate pharmacokinetics (PK), safety and efficacy of macitentan in children with pulmonary arterial hypertension (PAH).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Macitentan | Experimental | Drug: MacitentanMacitentan is administered once daily via oral route. Children less than (<) 2 years old (y.o.) will be assigned as a cohort to the macitentan group without randomization. The dose will be adjusted to the participant's age (for those < 2 y.o.) or to the participant's body weight (for those greater than or equal to (>=) 2 y.o.). single-arm extension period (SAEP) will start at end of core period (EOCP) visit and ends at end of study (EOS) visit. |
| Standard-of-care | Other | Other: Standard-of-careStandard-of-care as per site's clinical practice which may comprise treatment with pulmonary arterial hypertension (PAH) non-specific treatment and/or up to two PAH-specific medications excluding macitentan and intravenous/subcutaneous (IV/SC) prostanoids. |
Who may qualify
- Ages
- 1 month to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Signed informed consent by the parent(s) or legally designated representative and assent from developmentally capable children prior to initiation of any study-mandated procedure
- Males or females between greater than or equal to (>=) 1 month and less than (<) 18 years of age
- Participants with body weight >= 3.5 kilograms (kg) at randomization
- Pulmonary arterial hypertension (PAH) diagnosis confirmed by historical RHC (mPAP greater than or equal to [>=] 25 millimeters of mercury [mmHg], and Pulmonary artery wedge pressure [PAWP] less than or equal to [<=] 15 mmHg, and Pulmonary vascular resistance index [PVRi] greater than [>] 3 WU × m2), where in the absence of pulmonary vein obstruction and/or significant lung disease PAWP can be replaced by Left atrium pressure [LAP] or Left ventricular end diastolic pressure [LVEDP] (in absence of mitral stenosis) assessed by heart catheterization
- PAH belonging to the Nice 2013 Updated Classification Group 1 (including participants with Down Syndrome) and of following etiologies: idiopathic PAH; heritable PAH; PAH associated with congenital heart disease (CHD); Drug or toxin induced PAH; PAH associated with HIV; PAH associated with connective tissue diseases (PAH-aCTD); and World health organization (WHO) Functional class I to III
Key exclusion criteria (12 listed)
- Participants with PAH due to portal hypertension, schistosomiasis, or with pulmonary veno-occlusive disease and/or pulmonary capillary hemangiomatosis, and persistent pulmonary hypertension of the newborn
- Participants with PAH associated with Eisenmenger syndrome, or with moderate to large left-to-right shunts
- Participants receiving a combination of > 2 PAH-specific treatments at randomization.
- Treatment with intravenous (IV) or subcutaneous (SC) prostanoids within 4 weeks before randomization, unless given for vasoreactivity testing
- Hemoglobin or hematocrit <75 percent (%) of the lower limit of normal range
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-064992Dispersible tablet; Oral use | Drug | Macitentan |
| Standard-of-careStandard-of-care as per site's clinical practice which may comprise treatment with PAH non-specific treatment and/or up to two PAH-specific medications excluding macitentan and IV/SC prostanoids. | Other | Standard-of-care |
Primary outcome
Participants >=2 Years of Age: Observed Steady-State Trough (Pre-dose) Plasma Concentration of Macitentan and Aprocitentan (Active Metabolite) at Week 12 Based on Body Weight
Time frame: Pre-dose at Week 12
Observed steady-state trough (pre-dose) plasma concentration of macitentan and aprocitentan (active metabolite) at Week 12 based on body weight were reported. This outcome measure was planned to be analyzed for specified arms only.
Participants >=2 Years of Age: Observed Steady-State Trough (Pre-dose) Plasma Concentration of Macitentan and Aprocitentan (Active Metabolite) at Week 12 Based on Age Group
Time frame: Pre-dose at Week 12
Observed steady-state trough (pre-dose) plasma concentration of macitentan and aprocitentan (active metabolite) at Week 12 based on age group were reported. This outcome measure was planned to be analyzed for specified arms only.
Participants <2 Years of Age: Observed Steady-State Trough (Pre-dose) Plasma Concentration of Macitentan and Aprocitentan (Active Metabolite) at Week 4
Time frame: Pre-dose at Week 4
Observed steady-state trough (pre-dose) plasma concentration of macitentan and aprocitentan (active metabolite) at Week 4 were reported. This outcome measure was planned to be analyzed for specified arms only.
Participants From China With >=12 to <18 Years of Age: Observed Steady-State Trough (Pre-dose) Plasma Concentration of Macitentan and Aprocitentan (Active Metabolite) at Week 12
Time frame: Pre-dose at Week 12
Observed steady-state trough (pre-dose) plasma concentration of macitentan and aprocitentan (active metabolite) at Week 12 were reported.
19 secondary outcomes
Time to the First Clinical Event Committee (CEC)-Confirmed Disease Progression Event
Time frame: Baseline (Day 1) up to end of core study period (EOCP; up to 7.08 years)
Time to First CEC-confirmed Hospitalization for PAH
Time frame: Baseline (Day 1) up to EOCP (up to 7.08 years)
Time to CEC-confirmed Death Due to PAH
Time frame: Baseline (Day 1) up to EOCP (up to 7.08 years)
Time to Death (All Causes)
Time frame: Baseline (Day 1) up to 7.26 years
Percentage of Participants With World Health Organization (WHO) Functional Class (FC) I or II Versus III or IV
Time frame: At Weeks 12 and 24
Change From Baseline in N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) at Weeks 12 and 24
Time frame: Baseline (Day 1), Weeks 12 and 24
Change From Baseline in Mean Daily Time Spent in Moderate to Vigorous Physical Activity as Measured by Accelerometry at Week 48
Time frame: Baseline (Day 1), Week 48
Change From Baseline in Body Surface Area (BSA) Normalized Tricuspid Annular Plane Systolic Excursion (TAPSE) Measured by Echocardiography at Week 24
Time frame: Baseline (Day 1), Week 24
Change From Baseline in Left Ventricular Eccentricity Index (LVEI) Measured by Echocardiography at Week 24
Time frame: Baseline (Day 1), Week 24
Change From Baseline in Quality of Life Measured by Pediatric Quality of Life Inventory Version 4.0 (PedsQL 4.0) Generic Core Scales Short Form (SF-15)
Time frame: Baseline (Day 1), Week 24
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time frame: Baseline (Day 1) up to 7.26 years
Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs)
Time frame: Baseline (Day 1) up to 7.26 years
Number of Participants With AEs Leading to Premature Discontinuation of Macitentan or Standard of Care (SoC)
Time frame: Baseline (Day 1) up to 7.26 years
Number of Participants With AEs of Special Interest
Time frame: Baseline (Day 1) up to 7.26 years
Number of Participants With Marked Laboratory Abnormalities
Time frame: Baseline (Day 1) up to 7.26 years
Change From Baseline in Selected Laboratory Parameters
Time frame: Baseline (Day 1) up to 7.26 years
Change From Baseline in Vital Signs (Blood Pressure, Heart Rate)
Time frame: Baseline (Day 1) up to 7.26 years
Change From Baseline in Growth Variable
Time frame: Baseline (Day 1) up to 7.26 years
Change From Baseline in Sexual Maturation Measured by Tanner Stage
Time frame: Baseline (Day 1) up to 7.26 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41796854Berger RMF, Dunbar Ivy D, Borissoff JI, Cerovic S, Csonka D, Remenova T, Richard D, Villeneuve M, Beghetti M. Macitentan in Pediatric Pulmonary Arterial Hypertension (TOMORROW): A Randomized Clinical Trial. J Pediatr. 2026 Jun;293:115057. doi: 10.1016/j.jpeds.2026.115057. Epub 2026 Mar 6.
Related trials for Pulmonary Arterial Hypertension
RecruitingObservational study
Asthma and Primary Arterial Hypertension: an Inflammatory Link?
Asthma Bronchial
RecruitingPhase 1/2
HS235 Study in Overweight and Obese Participants With Combined Pre and Post-Capillary Pulmonary Hypertension Due to Heart Failure With Preserved Ejection Fraction
Pulmonary Hypertension, Heart Failure With Preserved Ejection Fraction
RecruitingPhase 2
Spironolactone for Pulmonary Arterial Hypertension
Pulmonary Arterial Hypertension
RecruitingPhase 1/2
A Study of HS235 for Treatment of Pulmonary Arterial Hypertension (PAH) in Adults
Pulmonary Arterial Hypertension
Active, not recruitingPhase 1
Study of Intravenous ZMA001 in Healthy Subjects
Pulmonary Arterial Hypertension PAH
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.
85 sites in 23 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Macitentan and Standard-of-care in people with Pulmonary Arterial Hypertension, run by Actelion at 85 sites in 23 countries.
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 6 inclusion and 12 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: finished, as of the sponsor's last update on 13 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 85 sites in United States, Russia, Spain, Mexico, China and 18 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. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 12 Sep 2025). 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?
Participants >=2 Years of Age: Observed Steady-State Trough (Pre-dose) Plasma Concentration of Macitentan and Aprocitentan (Active Metabolite) at Week 12 Based on Body Weight (time frame: Pre-dose at Week 12). The study lists 4 primary outcomes in all. 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 NCT02932410, which also lists 1 linked publication.
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 13 Mar 2026.