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.
1. Signed informed consent and willingness to accept either discontinuation or continuation of riociguat monotherapy
2. Age ≥18 years
WHO FC I or II
Pulmonary vascular resistance (PVR) < 3 Wood units
1. Background treatment with any PH-targeted therapy other than riociguat, (e.g., any endothelin receptor antagonist (ERA), phosphodiesterase-5 inhibitor (PDE-5i), parenteral prostanoids, prostacyclin receptor agonist)
2. Post-capillary pulmonary hypertension, defined as pulmonary artery wedge pressure (PAWP) > 15 mmHg
FEV₁ < 60% predicted, with FEV₁/FVC < 65%
and/or total lung capacity (TLC) < 60% predicted
Parallel
Discontinuation of riociguat
DrugDiscontinuation of riociguat after randomization
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
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)
To compare the effect of discontinuation versus continuation of riociguat monotherapy on WHO functionnal class
Change from baseline in WHO functionnal class
To compare the effect of discontinuation versus continuation of riociguat monotherapy on WHO functionnal class
Change from baseline in Borg dyspnea
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
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