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Pulmonary Arterial HypertensionPhase 4REPAIRNCT02310672

REPAIR: Right vEntricular Remodeling in Pulmonary ArterIal hypeRtension

A Phase 4 study testing Macitentan in people with Pulmonary Arterial Hypertension, run by Actelion at 41 sites in 12 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The study evaluates the effect of macitentan on right ventricular and hemodynamic properties in patients with symptomatic pulmonary arterial hypertension. Patients are treated with macitentan for 1 year. Patients undergo right heart catheterization (RHC) at baseline and Week 26. Read more about this study

Who is it for?
Ages 18 to 64 years
Conditions the study is for
Pulmonary Arterial Hypertension
What is being tested?
Macitentan
Could I receive a placebo?
No, everyone receives an active treatment
How many people
89 participants
Where
41 sitesin 12 countries
Study dates
1 Jun 2015to 10 Sep 2019
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 to 64 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Signed informed consent prior to any study-mandated procedure
  • Symptomatic pulmonary arterial hypertension (PAH)
  • World Health Organization (WHO) Functional Class (FC) I to III
  • PAH etiology belonging to one of the following groups according to Nice classification:
  • Idiopathic PAH
  • Heritable PAH
Show all 21Show fewer
  • Drug- and toxin-induced PAH
  • PAH associated with congenital heart diseases: only simple (atrial septal defect, ventricular septal defect, patent ductus arteriosus) congenital systemic to pulmonary shunts at least 2 year post surgical repair
  • Hemodynamic diagnosis of PAH confirmed by right heart catheterization (RHC) during screening showing:
  • mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg and
  • PCWP (pulmonary capillary wedge pressure) or left ventricular end diastolic pressure (LVEDP) ≤ 12 mmHg and pulmonary vascular resistance (PVR) ≥ 4 Wood Units (WU) (320 dyn.sec.cm-5) or
  • 12 mmHg ≤ PCWP or LVEDP ≤ 15 mmHg and PVR ≥ 6WU (480 dyn.sec.cm-5)
  • 6-minute walk distance (6MWD) ≥ 150 m during screening
  • For patients treated with oral diuretics, treatment dose must have been stable at least 1 month prior to RHC during the screening period
  • For patients treated with phosphodiesterase type-5 (PDE-5) inhibitors, treatment dose must have been stable at least 3 months prior to RHC during the screening period
  • For patients treated with beta blockers, treatment dose must have been stable at least 1 month prior to the RHC during the screening period
  • Men or women ≥18 and < 65 years
  • Women of childbearing potential (defined in protocol) must:
  • Have a negative serum pregnancy test during screening and a negative urine pregnancy test on Day 1, and
  • Agree to use reliable methods of contraception (defined in protocol) from screening up to 30 days after study treatment discontinuation, and
  • Agree to perform monthly pregnancy tests up to 30 days after study treatment discontinuation

Who cannot join

  • Body weight < 40 kg
  • Body mass index (BMI) > 35kg/m2. For patients with 30kg/m2 < BMI < 35kg/m2, an eligibility form will be submitted to a Steering Committee member who will reserve the right to exclude the patient.
  • Pregnancy, breastfeeding or intention to become pregnant during the study
  • Recently started (< 8 weeks prior to informed consent signature) or planned cardio-pulmonary rehabilitation program
  • Known concomitant life-threatening disease with a life expectancy < 12 months
  • Any condition likely to affect protocol or treatment compliance
Show all 38Show fewer
  • Hospitalization for PAH within 3 months prior to informed consent signature
  • Left atrial volume indexed for body surface area ≥ 43mL/m2 by echocardiography or cardiac MRI
  • Valvular disease grade 2 or higher
  • History of pulmonary embolism or deep vein thrombosis
  • Documented moderate to severe chronic obstructive pulmonary disease
  • Documented moderate to severe restrictive lung disease
  • Historical evidence of significant coronary artery disease established by:
  • History of myocardial infarction or
  • More than 50% stenosis in a coronary artery (by percutaneous coronary intervention or angiography) or
  • Elevation of the ST segment on electrocardiogram or
  • History of coronary artery bypass grafting or
  • Stable angina
  • Diabetes mellitus
  • Moderate to severe renal insufficiency (calculated creatinine clearance < 60 mL/min/1.73 m2)
  • Cancer
  • Systolic blood pressure < 90 mmHg
  • Severe hepatic impairment (with or without cirrhosis) according to National Cancer Institute organ dysfunction working group criteria, defined as total bilirubin > 3 × upper limit of the normal range (ULN) accompanied by an aspartate aminotransferase (AST) elevation > ULN at Screening.
  • Hemoglobin < 100g/L
  • AST and/or alanine aminotransferase (ALT) > 3× ULN
  • Need for dialysis
  • Responders to acute vasoreactivity test based on medical history
  • Prior use of endothelin receptor antagonists (ERAs), stimulators of soluble guanylate cyclase or prostacyclin or prostacyclin analogues
  • Treatment with strong inducers of cytochrome P450 isozyme 3A4 (CYP3A4) within 4 weeks prior to study treatment initiation (e.g., carbamazepine, rifampicin, rifabutin, phenytoin and St. John's Wort)
  • Treatment with strong inhibitors of CYP3A4 within 4 weeks prior to study treatment initiation (e.g., ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, nefazodone, ritonavir, and saquinavir)
  • Treatment with another investigational drug (planned, or taken within the 3 months prior to study treatment initiation).
  • Hypersensitivity to any ERA or any excipients of the formulation of macitentan (lactose, magnesium stearate, microcrystalline cellulose, povidone, sodium starch glycolate, polyvinyl alcohol, polysorbate, titanium dioxide, talc, xanthan gum, and lecithin soya)
  • Claustrophobia
  • Permanent cardiac pacemaker, automatic internal cardioverter
  • Metallic implant (e.g., defibrillator, neurostimulator, hearing aid, permanent use of infusion device)
  • Atrial fibrillation, multiple premature ventricular or atrial contractions, or any other condition that would interfere with proper cardiac gating during MRI.
  • For patients enrolling in the metabolism sub-study only: glucose intolerance
  • For patients enrolling in the biopsy sub-study only: PAH etiology belonging to Nice classification 1.4.4: PAH associated with congenital heart diseases

Trial locations and contacts

41 sites in 12 countries.

41 sites in 12 countries

United States8 sites

  • Massachussetts General Hospital

    Boston, Massachusetts, 02114

  • University of Texas Southwestern Medical

    Dallas, Texas, 75390

  • St. Luke's Medical Center

    Milwaukee, Wisconsin, 53215

  • University of Minnesota

    Minneapolis, Minnesota, 55455

  • Rudgers New Jersey Medical School

    New Brunswick, New Jersey, 08901

  • Cornell University

    New York, New York, 10065

  • University of Pittsburgh Medical Center

    Pittsburgh, Pennsylvania, 15213

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

France7 sites

  • Hopital Gabriel Montpied

    Clermont-Ferrand, 63003

  • Hôpital Michallon

    La Tronche, 38700

  • "CHRU de Lille - Hôpital Albert Calmette "

    Lille, 59037

  • Hopital de Brabois

    Nancy, 54511

  • Hôpital Laennec

    Nantes, 44093

  • Hôpital Pasteur

    Nice, 06002

  • Hôpital Européen Georges-Pompidou

    Paris, 75015

Other trials in France

Netherlands5 sites

  • VU University Medical Center (VUMC)

    Amsterdam, 1081 HV

  • Maastricht UMC+

    Maastricht, 6229

  • St. Antonius Ziekenhuis

    Nieuwegein, 3435 CM

  • Radboud UMC

    Nijmegen, 6525 GA

  • Erasmus University medical Center

    Rotterdam, 3000 CA

Other trials in Netherlands

Germany4 sites

  • Medizinische Klinik und Poliklinik II Universitätsklinik Bonn

    Bonn, 53105

  • Universitätsklinikum Köln Herzzentrum / Klinik III für Innere Medizin

    Cologne, 50924

  • Thoraxklinik am Universitätsklinikum Heidelberg

    Heidelberg, 69126

  • Universitätsmedizin der Johannes Gutenberg-Universität Mainz Centrum für Thrombose und Hämostase

    Mainz, 55131

Other trials in Germany

Hong Kong3 sites

  • Grantham Hospital, Cardiac Medical Unit

    Hong Kong, 999077

  • Queen Mary Hospital

    Hong Kong, 999077

  • United Christian Hospital

    Hong Kong, 999077

Other trials in Hong Kong

United Kingdom3 sites

  • Golden Jubilee National Hospital

    Glasgow, G81 4DY

  • The Royal Free Hospital

    London, NW3 2QG

  • "Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital"

    Sheffield, S10 2JF

Other trials in United Kingdom

Israel2 sites

  • Pulmonology institute, Soroka Medical Center

    Beersheba, 84101

  • Shaare Zedek Medical Center

    Jerusalem, 9103102

Other trials in Israel

Italy2 sites

  • Policlinico Sant'Orsola-Malpighi

    Bologna, 40138

  • Fondazione IRCCS Policlinico San Matteo Ambulatorio Scompenso Cardiaco e Trapianti

    Pavia, 27100

Other trials in Italy

Malaysia2 sites

  • Hospital Pulau Pinang

    George Town, 10990

  • Institut Jantung Negara (National Heart Institute)

    Kuala Lumpur, 50400

Other trials in Malaysia

Russia2 sites

  • Russian Cardiology Scientific and Production Complex

    Moscow, 121552

  • Almazov Federal North-West Medical Research Centre of Department of Health

    Saint Petersburg, 197341

Other trials in Russia

Singapore2 sites

  • National University Hospital - The Heart Institute - Cardiac Department

    Singapore, 119228

  • National Heart Centre (NHC) Singapore

    Singapore, 169609

Other trials in Singapore

Australia1 site

  • The Prince Charles Hospital

    Chermside, Queensland, 4032

Other trials in Australia

About this study

Official title: A Prospective, Multicenter, Single-arm, Open-label, Phase 4 Study to Evaluate the Effects of Macitentan on Right vEntricular Remodeling in Pulmonary ArterIal hypeRtension Assessed by Cardiac Magnetic Resonance Imaging

The study evaluates the effect of macitentan on right ventricular and hemodynamic properties in patients with symptomatic pulmonary arterial hypertension. Patients are treated with macitentan for 1 year. Patients undergo right heart catheterization (RHC) at baseline and Week 26. They also undergo cardiac magnetic resonance imaging (MRI) at baseline, Week 26 and Week 52. Safety is monitored throughout the study. The study has three stub-studies. Each patient can participate in no sub-study or in one sub-study. The sub-studies are: (1) metabolism sub-study (with PET-MR scans); (2) biopsy sub-study (biopsies taken during the RHC); (3) Echo sub-study.

Being tested
Macitentan
Keywords
Pulmonary Arterial Hypertension
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

    All patients take open-label macitentan 10mg o.d.

Study groups in NCT02310672
Study groupRoleWhat they receive
MacitentanExperimentalAll patients take open-label macitentan 10mg o.d.
Receives: Drug: Macitentan

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change From Baseline in Right Ventricular Stroke Volume (RVSV) to Week 26

    Change from baseline in RVSV assessed by cardiac magnetic resonance imaging (MRI) from pulmonary artery flow was reported at Week 26. Primary analysis were based on interim results as pre-planned and the primary outcome measures data table reported is finalized as is.

    Measured: Baseline and Week 26

  2. Ratio of Week 26 to Baseline Pulmonary Vascular Resistance (PVR)

    Ratio of Week 26 to baseline PVR as assessed by RHC was reported. PVR represents the resistance against which the right ventricle needs to pump. PVR is determined by right heart catheterization (RHC). PVR was calculated as 80*(Mean pulmonary arterial pressure [mPAP] -[Pulmonary capillary wedge pressure {PCWP} or Left ventricular end diastolic pressure {LVEDP} if PCWP not available/cardiac output [CO]). Primary analysis were based on interim results as pre-planned and the primary outcome measures data table reported is finalized as is.

    Measured: Baseline and Week 26

Secondary outcomes (6)

  1. Change From Baseline in Right Ventricular End Diastolic Volume (RVEDV) to Week 26

    Change from baseline to Week 26 in RVEDV assessed by cardiac MRI was reported.

    Measured: Baseline to Week 26

  2. Change From Baseline in Right Ventricular End Systolic Volume (RVESV) to Week 26

    Change from baseline to Week 26 in RVESV assessed by cardiac MRI was reported.

    Measured: Baseline to Week 26

  3. Change From Baseline in Right Ventricular Ejection Fraction (RVEF) to Week 26 (% Blood Volume)

    Change from baseline to Week 26 in RVEF based on pulmonary artery flow assessed by cardiac MRI was reported.

    Measured: Baseline to Week 26

  4. Change From Baseline in Right Ventricle (RV) Mass to Week 26

    Change from baseline to Week 26 in RV mass assessed by cardiac MRI was reported.

    Measured: Baseline to Week 26

  5. Change From Baseline in Six-minutes Walk Distance (6MWD) to Week 26

    6MWD is a non-encouraged test performed in a 30 meter (m) long flat corridor, where the participant is instructed to walk as far as possible, back and forth around two cones, with the permission to slow down, rest, or stop if needed. This test is used to assess exercise capacity. The test was performed about 30 minutes after study drug administration. Any increase in the walk distance was considered improvement from baseline.

    Measured: Baseline to Week 26

  6. Change From Baseline in World Health Organization Functional Class (WHO FC) to Week 26

    WHO FC is a classification which reflects disease severity based on symptoms. WHO Functional Classification of pulmonary hypertension comprises of Class I (participants with pulmonary hypertension but without resulting limitation of physical activity), II (participants with pulmonary hypertension resulting in slight limitation of physical activity), III (participants with pulmonary hypertension resulting in marked limitation of physical activity) and IV (participants with pulmonary hypertension with inability to carry out any physical activity without symptoms). Changes from baseline to Week 26 included: improvement (change from a higher to a lower FC), worsening (change from a lower to a higher FC) or unchanged/stable (same FC at baseline and at the post-baseline time point).

    Measured: Baseline to Week 26

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Dec 2014 (estimated)
  2. Study start1 Jun 2015
  3. Primary completion10 Sep 2019
  4. Study completion10 Sep 2019

Resources

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
89 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02310672
Sponsor's protocol ID
AC-055-403
Acronym
REPAIR
Status last verified
Mar 2025
First submitted
4 Dec 2014
Last updated
30 Mar 2025
Data monitoring committee
No

Publications

  • Kiely DG, Channick R, Flores D, Galie N, MacDonald G, Marcus JT, Mitchell L, Peacock A, Rosenkranz S, Tawakol A, Torbicki A, Vonk Noordegraaf A, Swift AJ. Comparison of cardiac magnetic resonance imaging, functional and haemodynamic variables in pulmonary arterial hypertension: insights from REPAIR. ERJ Open Res. 2024 Feb 12;10(1):00547-2023. doi: 10.1183/23120541.00547-2023. eCollection 2024 Jan.

    PubMed 38348238

  • Torbicki A, Channick R, Galie N, Kiely DG, Moceri P, Peacock A, Swift AJ, Tawakol A, Vonk Noordegraaf A, Flores D, Martin N, Rosenkranz S. Effect of Macitentan in Pulmonary Arterial Hypertension and the Relationship Between Echocardiography and cMRI Variables: REPAIR Echocardiography Sub-study Results. Cardiol Ther. 2024 Mar;13(1):173-190. doi: 10.1007/s40119-023-00345-2. Epub 2024 Jan 28.

    PubMed 38281309

  • Vonk Noordegraaf A, Channick R, Cottreel E, Kiely DG, Marcus JT, Martin N, Moiseeva O, Peacock A, Swift AJ, Tawakol A, Torbicki A, Rosenkranz S, Galie N. The REPAIR Study: Effects of Macitentan on RV Structure and Function in Pulmonary Arterial Hypertension. JACC Cardiovasc Imaging. 2022 Feb;15(2):240-253. doi: 10.1016/j.jcmg.2021.07.027. Epub 2021 Nov 17.

    PubMed 34801462

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Macitentan in people with Pulmonary Arterial Hypertension, run by Actelion at 41 sites in 12 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 21 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: 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 41 sites in United States, France, Netherlands, Germany, Hong Kong and 7 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 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 24 Sep 2020). 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?

Change From Baseline in Right Ventricular Stroke Volume (RVSV) to Week 26 (time frame: Baseline and Week 26). The study lists 2 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 NCT02310672, which also lists 3 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.

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