Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare but severe complication of acute pulmonary embolism, characterized by persistent obstruction of the pulmonary arteries by organized thrombi and secondary microvasculopathy. International guidelines recommend a multimodal approach combining pulmonary endarterectomy (PEA), balloon pulmonary angioplasty (BPA), and medical treatment with riociguat, to address the full spectrum of CTEPH lesions. BPA and riociguat are recommended for symptomatic patients with inoperable CTEPH or persistent pulmonary hypertension after PEA. Riociguat is administered before BPA to reduce periprocedural complications by improving pulmonary hemodynamics. While this pre-BPA strategy is well established, post-BPA management is poorly studied, especially in patients achieving therapeutic goals, defined as WHO functional class I or II and near-normal resting pulmonary hemodynamics (70 to 80% of cases). In such cases, riociguat monotherapy is often continued long-term, despite its cost, burden, and potential side effects, which may negatively impact patients' quality of life. Retrospective single-center studies suggest that discontinuation of medical treatment does not lead to significant clinical deterioration. Therefore, we propose conducting a multicenter trial using a PROBE (prospective, randomized, open-label, blinded endpoint) design and a Bayesian approach to test if stopping riociguat monotherapy after successful BPA is associated with an acceptably low risk of clinical worsening over a follow-up period of at least one year compared to continuation. The trial will also assess the cost-effectiveness of riociguat discontinuation.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
150
Discontinuation of riociguat after randomization
CHU Angers
Angers, France
Hôpital Haut Levêque
Bordeaux, France
Hôpital de la Cavale blanche
Brest, France
CHU Caen
Caen, France
Hôpital Gabriel Montpied
Clermont-Ferrand, France
CHU Dijon Bourgogne
Dijon, France
CHU Grenoble Alpes
Grenoble, France
Hôpital Bicêtre
Le Kremlin-Bicêtre, France
Institut Cœur-Poumon
Lille, France
Hôpital de la Timone
Marseille, France
...and 12 more locations
To evaluate whether the discontinuation of riociguat monotherapy after successful BPA in CTEPH patients is associated with an acceptably low risk of clinical worsening compared to continuation
Clinical worsening which is the composite of : * death due to any cause, * hospitalisation due to worsening including : a) documented right heart failure, b) need for lung transplantation, c) need for intraveinous diuretics/inotropic support or d) need for parental prostanoids * decline in 6 minutes walk distance by 15% from baseline, combined with WHO functional class III or IV
Time frame: At the longest follow-up, minimum 12 months
To compare the effect of discontinuation versus continuation of riociguat monotherapy on 6-minute walk distance (6MWD)
Change from baseline in 6-minute walk distance (6MWD)
Time frame: Month 3, 6, 12 and every 6 months with maximum of 48 months
To compare the effect of discontinuation versus continuation of riociguat monotherapy on WHO functionnal class
Change from baseline in WHO functionnal class
Time frame: Month 3, 6, 12 and every 6 months with maximum of 48 months
To compare the effect of discontinuation versus continuation of riociguat monotherapy on WHO functionnal class
Change from baseline in Borg dyspnea
Time frame: Month 3, 6, 12 and every 6 months with maximum of 48 months
To compare the effect of discontinuation versus continuation of riociguat monotherapy on other clinical measures of pulmonary hypertension
Change from baseline in N-terminal pro-brain natriuretic peptide (NT-proBNP) levels
Time frame: Month 3, 6, 12 and every 6 months with maximum of 48 months
To compare the effect of discontinuation versus continuation of riociguat monotherapy on pulmonary vascular resistance (PVR)
Change from baseline in Pulmonary vascular resistance (PVR)
Time frame: Month 12
To compare the effect of discontinuation versus continuation of riociguat monotherapy on hemodynamic parameters :
Change from baseline in Right atrial pressure
Time frame: Month 12
To compare the effect of discontinuation versus continuation of riociguat monotherapy on hemodynamic parameters
Change from baseline in Mean pulmonary arterial pressure (mPAP)
Time frame: Month 12
To compare the effect of discontinuation versus continuation of riociguat monotherapy on hemodynamic parameters
Change from baseline in Cardiac output
Time frame: Month 12
To compare the effect of discontinuation versus continuation of riociguat monotherapy on quality of life
Change from baseline in EQ-5D-5L questionnaire
Time frame: Month 3, 6, 12 and every 6 months with maximum of 48 months
To compare the effect of discontinuation versus continuation of riociguat monotherapy on quality of life
Change from baseline in EmPHasis-10 questionnaire (scale from 0 (best) to 5 (worst)
Time frame: Month 3, 6, 12 and every 6 months with maximum of 48 months
To assess the health economic impact of riociguat discontinuation
Incremental cost-effectiveness ratio (ICER), defined as the difference in in quality-adjusted life years (QALYS), for the strategy of riociguat monotherapy discontinuation from the perspective of the French public health system
Time frame: At the longest follow-up, minimum 12 months
To assess treatment burden
Change from baseline in Treatment burden questionnaire
Time frame: Month 12
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