REPAIR: Right vEntricular Remodeling in Pulmonary ArterIal hypeRtension

NCT02310672 | Completed Phase 4 Results

• 1 other identifier: AC-055-403
• Study Type: interventional
• Target: 89
• Locations: 12 countries
• Sites: 41

Brief 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. 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.

Conditions

Pulmonary Arterial Hypertension

Keywords

Pulmonary Arterial Hypertension

Outcome Measures

Primary Outcomes (2)

• 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.

  Baseline and Week 26

• 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.

  Baseline and Week 26

Secondary Outcomes (6)

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

  Baseline to Week 26

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

  Baseline to Week 26

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

  Baseline to Week 26

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

  Baseline to Week 26

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

  Baseline to Week 26

Study Arms (1)

Macitentan

EXPERIMENTAL

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

Drug: Macitentan

Interventions

Macitentan DRUG

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

Also known as: ACT-064992

Macitentan

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• 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
• mmHg ≤ PCWP or LVEDP ≤ 15 mmHg and PVR ≥ 6WU (480 dyn.sec.cm-5)
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Actelion: lead

Study Sites (41)

Massachussetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Rudgers New Jersey Medical School

New Brunswick, New Jersey, 08901, United States

Location

Cornell University

New York, New York, 10065, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Texas Southwestern Medical

Dallas, Texas, 75390, United States

Location

St. Luke's Medical Center

Milwaukee, Wisconsin, 53215, United States

Location

The Prince Charles Hospital

Chermside, Queensland, 4032, Australia

Location

Hopital Gabriel Montpied

Clermont-Ferrand, 63003, France

Location

Hôpital Michallon

La Tronche, 38700, France

Location

"CHRU de Lille - Hôpital Albert Calmette "

Lille, 59037, France

Location

Hopital de Brabois

Nancy, 54511, France

Location

Hôpital Laennec

Nantes, 44093, France

Location

Hôpital Pasteur

Nice, 06002, France

Location

Hôpital Européen Georges-Pompidou

Paris, 75015, France

Location

Medizinische Klinik und Poliklinik II Universitätsklinik Bonn

Bonn, 53105, Germany

Location

Universitätsklinikum Köln Herzzentrum / Klinik III für Innere Medizin

Cologne, 50924, Germany

Location

Thoraxklinik am Universitätsklinikum Heidelberg

Heidelberg, 69126, Germany

Location

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

Mainz, 55131, Germany

Location

Grantham Hospital, Cardiac Medical Unit

Hong Kong, 999077, Hong Kong

Location

Queen Mary Hospital

Hong Kong, 999077, Hong Kong

Location

United Christian Hospital

Hong Kong, 999077, Hong Kong

Location

Pulmonology institute, Soroka Medical Center

Beersheba, 84101, Israel

Location

Shaare Zedek Medical Center

Jerusalem, 9103102, Israel

Location

Policlinico Sant'Orsola-Malpighi

Bologna, 40138, Italy

Location

Fondazione IRCCS Policlinico San Matteo Ambulatorio Scompenso Cardiaco e Trapianti

Pavia, 27100, Italy

Location

Hospital Pulau Pinang

George Town, 10990, Malaysia

Location

Institut Jantung Negara (National Heart Institute)

Kuala Lumpur, 50400, Malaysia

Location

VU University Medical Center (VUMC)

Amsterdam, 1081 HV, Netherlands

Location

Maastricht UMC+

Maastricht, 6229, Netherlands

Location

St. Antonius Ziekenhuis

Nieuwegein, 3435 CM, Netherlands

Location

Radboud UMC

Nijmegen, 6525 GA, Netherlands

Location

Erasmus University medical Center

Rotterdam, 3000 CA, Netherlands

Location

Russian Cardiology Scientific and Production Complex

Moscow, 121552, Russia

Location

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

Saint Petersburg, 197341, Russia

Location

National University Hospital - The Heart Institute - Cardiac Department

Singapore, 119228, Singapore

Location

National Heart Centre (NHC) Singapore

Singapore, 169609, Singapore

Location

Golden Jubilee National Hospital

Glasgow, G81 4DY, United Kingdom

Location

The Royal Free Hospital

London, NW3 2QG, United Kingdom

Location

"Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital"

Sheffield, S10 2JF, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 38348238 DERIVED

• 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.

  PMID: 38281309 DERIVED

• 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.

  PMID: 34801462 DERIVED

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

macitentan

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

Due to the open-label non-comparative design of study, it cannot be excluded that 6MWD and WHO FC could have been influenced by participants' knowledge that they did receive an active treatment whose efficacy had already been demonstrated.

Results Point of Contact

• Title: Director
• Organization: Actelion Pharmaceuticals Ltd

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Loïc Perchenet

  Actelion

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 4, 2014
• First Posted: December 8, 2014
• Study Start: June 1, 2015
• Primary Completion: September 10, 2019
• Study Completion: September 10, 2019
• Last Updated: March 30, 2025
• Results First Posted: September 24, 2020

Record last verified: 2025-03

Locations

FR (7); NL (5); US (8); SG (2); MY (2); AU (1); HK (3); IL (2); GB (3); DE (4); IT (2); RU (2)