Riociguat Versus Balloon Pulmonary Angioplasty in Non-operable Chronic thromboEmbolic Pulmonary Hypertension

NCT02634203 | Completed DMC

• 2 other identifiers: AOM141232015-A00973-46
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 1

Brief Summary

"Chronic thromboembolic pulmonary hypertension (CTEPH) is a severe form of pulmonary hypertension characterized by obstruction of the pulmonary vasculature by residual organized thrombi, leading to increased pulmonary vascular resistance (PVR), progressive pulmonary hypertension, and right failure. In patients deemed operable, pulmonary endarterectomy (PEA) is the gold standard treatment and is the only potentially curative treatment. However, some patients are ineligible for surgery owing to occlusion of distal vessels. The best treatment option for these non-operable CTEPH patients is not yet established.

Conditions

Chronic Thromboembolic Pulmonary Hypertension

Keywords

Chronic Thromboembolic Pulmonary Hypertension; Balloon Pulmonary Angioplasty; Riociguat

Outcome Measures

Primary Outcomes (1)

• Change from baseline in Pulmonary Vascular Resistance (PVR)

  Pulmonary Vascular Resistance (PVR)

  Baseline and at 26 weeks

Secondary Outcomes (5)

• Change from Baseline in 6 Minute Walking Distance (6MWD)

  Baseline and at 26 weeks

• Change from Baseline in WHO (World Health Organization) functional class (FC)

  Baseline and at 26 weeks

• Change from baseline in NT PRO-BNP

  Baseline and at 26 weeks

• Change from Baseline in Borg dyspnea score (measured at the end of the 6MWD Test

  Baseline and at 26 weeks

• Time To Clinical Worsening defined by the occurence of - Death (all-cause mortality or Lung) - or Heart-lung transplantation - or Hospitalization due to persistent worsening of PH or - Start of PAH specific treatment

  Up to 26 weeks

Study Arms (2)

Balloon Pulmonary Angioplasty (BPA)

EXPERIMENTAL

Non-operable patients with CTEPH allocated to BPA arm

Procedure: Balloon Pulmonary Angioplasty (BPA)

Riociguat

ACTIVE COMPARATOR

Non-operable patients with CTEPH allocated to Riociguat arm

Drug: Riociguat

Interventions

Balloon Pulmonary Angioplasty (BPA) PROCEDURE

Balloon pulmonary angioplasty (BPA) will be done via femoral vein. 2 sessions will be performed during the same hospitalization following by additional sessions at an interval of 2-3 weeks until a mean PAP\< 30 mmHg is achieved A pulmonary angiography and a right heart catheterization will be performed at each BPA session

Balloon Pulmonary Angioplasty (BPA)

Riociguat DRUG

The starting dose will be 1 mg three times daily as recommended. The dose will be titrated every 2 weeks according to the peripheral systolic pressure. Dose should be increased by 0.5 mg three times daily every two weeks to a maximum of 2.5 mg three times daily, if systolic blood pressure is ≥95 mmHg and the patient has no signs or symptoms of hypotension.

Also known as: Medical therapy with Riociguat

Riociguat

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• to 80 years of age at Visit 1
• CTEPH patients considered as non-operable but eligible for balloon pulmonary angioplasty and riociguat by the multidisciplinary meeting, with pulmonary vascular resistance \> 320 dyn.sec.cm-5 and mean PAP \> 25 mmHg and PWP (Pulmonary capillary Wedge Pressure) ≤ 15 mmHg measured at least 3 months after start of full anticoagulation. If the patient is treated with new oral anticoagulants drugs, NOAC's, (rivaroxaban, apixaban, dabigatran), the treatment should be switched to Vitamin K antagonist (VKA).
• The diagnosis of CTEPH must have been established based on 2 of the 3 following methods before study entry: ventilation-perfusion scan, pulmonary angiography, spiral-CT scan.
• The diagnosis of inoperability must have been established based on spiral-CT scan and/or pulmonary angiography before study entry.
• Unspecific treatments which may also be used for the treatment of pulmonary hypertension (PH) such as oral anticoagulants, diuretics, digitalis, calcium channel blockers or oxygen supplementation are permitted. However treatment with anticoagulants must have been started at least 3 months before Visit 1.
• Specific PH treatments (bosentan, ambrisentan, macitentan, sildenafil, tadalafil, epoprostenol, treprostinil, iloprost) are not permitted at Visit 1.
• Patients who fulfill criteria for a supplemental long-term oxygen therapy (PaO2 \< 55 mmHg at rest) need to be supplied sufficiently before study entry. The amount of supplemental oxygen and the delivery method need to be stable for at least one month before Visit 1.
• Right-heart catheterization results for the definite diagnosis of PH must not be older than 6 weeks at Visit 1 (will be considered as baseline values), must have been measured after at least 3 months of full anticoagulation, and must have been measured in the participating center under standardized conditions.
• Women without childbearing potential defined as postmenopausal women aged 55 years or older, women with bilateral tubal ligation, women with bilateral ovarectomy, and women with hysterectomy can be included in the study. Women with childbearing potential can be included in the study only if a serological pregnancy test is negative and a combination of condoms with a safe and highly effective contraception method is used.
• Patients who are able to understand and follow instructions and who are able to participate in the study for the entire period.
• Patients must have given their written informed consent to participate in the study after having received adequate previous information and prior to any study-specific procedures.

You may not qualify if:

• Participation in another clinical trial during the preceding 3 months.
• Pregnant women, or breast feeding women, or women with childbearing potential not using a combination of condoms and a safe and highly effective contraception method (hormonal contraception with implants or oral contraceptives, intrauterine devices ).
• Patients with a medical disorder, condition, or history of such that would impair the patient's ability to participate or complete this study in the opinion of the investigator.
• Patients with underlying medical disorders and anticipated life expectancy below 2 years (eg active cancer disease with localized and/or metastasized tumor mass).
• Patients with a history of severe allergic-like reaction to intravascular administration of iodinated contrast media (including diffuse edema or facial edema with dyspnea, diffuse erythema with hypotension, laryngeal edema with stridor and/or hypoxia, bronchospasm, anaphylactic shock with hypotension and tachycardia)
• Significant obstructive or restrictive lung disease (forced expiratory volume \< 60% predicted and/or total lung capacity \< 70% predicted).
• Severe hepatic impairment (Child-Pugh C)
• Left heart failure with an ejection fraction less than 40%
• Severe proven or suspected coronary artery disease (symptomatic patients with Canadian Cardiovascular Society Angina Classification class 2-4, and/or requiring nitrates, and/or myocardial infarction within the last 3 months before Visit 1).
• Severe renal insufficiency (glomerular filtration rate ≤ 30mL/min eg calculated based on the Cockcroft formula).
• Patient not covered by social security service
• Patients with significant interstitial lung disease on High-resolution computed tomography (HRCT)
• Patients with hypersensitivity to riociguat or any of the excipients.
• Treatment with :
• PDE-5 Inhibitors (eg Sildenafil or Tadalafil)

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Bayer: collaborator

Study Sites (1)

AP-HP, Bicêtre Hospital

Le Kremlin-Bicêtre, 94275, France

Location

Related Publications (2)

• Gerges C, Jevnikar M, Brenot P, Savale L, Beurnier A, Bouvaist H, Sitbon O, Fadel E, Boucly A, Chemla D, Simonneau G, Humbert M, Montani D, Jais X; RACE Investigators. Effect of Balloon Pulmonary Angioplasty and Riociguat on Right Ventricular Afterload and Function in CTEPH: Insights From the RACE Trial. Circ Cardiovasc Interv. 2025 Feb;18(2):e014785. doi: 10.1161/CIRCINTERVENTIONS.124.014785. Epub 2025 Feb 18.

  PMID: 39965044 DERIVED

• Jais X, Brenot P, Bouvaist H, Jevnikar M, Canuet M, Chabanne C, Chaouat A, Cottin V, De Groote P, Favrolt N, Horeau-Langlard D, Magro P, Savale L, Prevot G, Renard S, Sitbon O, Parent F, Tresorier R, Tromeur C, Piedvache C, Grimaldi L, Fadel E, Montani D, Humbert M, Simonneau G. Balloon pulmonary angioplasty versus riociguat for the treatment of inoperable chronic thromboembolic pulmonary hypertension (RACE): a multicentre, phase 3, open-label, randomised controlled trial and ancillary follow-up study. Lancet Respir Med. 2022 Oct;10(10):961-971. doi: 10.1016/S2213-2600(22)00214-4. Epub 2022 Aug 1.

  PMID: 35926542 DERIVED

MeSH Terms

Interventions

riociguat

Study Officials

• Xavier JAIS, MD, PhDI

  AP-HP, Bicêtre Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2015
• First Posted: December 17, 2015
• Study Start: January 19, 2016
• Primary Completion: January 27, 2020
• Study Completion: January 27, 2020
• Last Updated: January 26, 2021

Record last verified: 2017-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)