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

• Register: ClinicalTrials.gov
• Last refreshed on: 1 February 2021
• Main ID: NCT02634203
• Date of registration: 08/12/2015
• Prospective Registration: Yes
• Primary sponsor: Assistance Publique - Hôpitaux de Paris
• Public title: Riociguat Versus Balloon Pulmonary Angioplasty in Non-operable Chronic thromboEmbolic Pulmonary Hypertension RACE
• Scientific title: Riociguat Versus Balloon Pulmonary Angioplasty in Non-operable Chronic thromboEmbolic Pulmonary Hypertension
• Date of first enrolment: January 19, 2016
• Target sample size: 105
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02634203
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: N/A

Countries of recruitment

France

Contacts

• Name: Xavier JAIS, MD, PhDI
• Affiliation: AP-HP, Bicêtre Hospital

Key inclusion & exclusion criteria

Inclusion Criteria:

- 18 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.

Exclusion Criteria:

- 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

Non-inclusion criteria related to treatment by riociguat:

- 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)

- NO donors (eg Nitrates)

- Strong multi pathway cytochrome P450 (CYP) and P-glycoprotein (P-gp) / breast cancer
resistance protein (BCRP) inhibitors such as azole antimycotics (e.g. ketoconazole,
itraconazole) or HIV protease inhibitors (e.g. ritonavir)

- Systolic blood pressure <95mmHg

- Patients with a history of life-threatening hemoptysis (>100 mL in 24 h) or who have
previously undergone bronchial arterial embolization for hemoptysis

Non-inclusion criteria related to BPA:

• Patients who could not remain in a supine position for at least 120 min for any reason.

Very distal CTEPH disease without stenosis, webs, or slits on CT scan and CTEPH disease
with predominant complete occlusions of segmental or sub- segmental arteries (defined by
the multidisciplinary meeting)



Age minimum: 18 Years
Age maximum: 80 Years
Gender: All

Health Condition(s) or Problem(s) studied

Chronic Thromboembolic Pulmonary Hypertension

Intervention(s)

Drug: Riociguat

Procedure: Balloon Pulmonary Angioplasty (BPA)

Primary Outcome(s)

Change from baseline in Pulmonary Vascular Resistance (PVR) [Time Frame: Baseline and at 26 weeks]

Secondary Outcome(s)

Change from Baseline in Borg dyspnea score (measured at the end of the 6MWD Test [Time Frame: Baseline and at 26 weeks]

Change from Baseline in 6 Minute Walking Distance (6MWD) [Time Frame: Baseline and at 26 weeks]

Change from baseline in NT PRO-BNP [Time Frame: 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 [Time Frame: Up to 26 weeks]

Change from Baseline in WHO (World Health Organization) functional class (FC) [Time Frame: Baseline and at 26 weeks]

Secondary ID(s)

AOM14123

2015-A00973-46

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Bayer