In patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH), riociguat pretreatment may improve hemodynamics before the use of balloon pulmonary angioplasty (BPA). In particular, BPA does not replace medical treatment with riociguat in these patients. These were part of clinical trial results published in Respiratory Medicine The Lancet.
Recognizing the lack of randomized trials comparing the use of riociguat and BPA as treatment options for patients with inoperable CTEPH, researchers sought to assess the efficacy and safety of BPA versus riociguat in patients with this disease.
Researchers conducted a controlled, randomized, multicenter, open-label, parallel-group Phase 3 RACE trial (ClinicalTrials.gov identifier: NCT02634203) in 23 French centers with expertise in the treatment of PH. Between January 2016 and January 2019, the trial enrolled 105 treatment-naïve patients between the ages of 18 and 80, with newly diagnosed and inoperable CTEPH and a pulmonary vascular resistance (PVR) of more than 320 dyn/s/cm5. All patients were randomly assigned in a 1:1 ratio to BPA (n=52) or riociguat (n=53) via an online randomization system.
The primary endpoint of the study was the change in PVR at week 26, expressed as a percentage of baseline PVR in the intention-to-treat population. Tolerance analyzes were carried out in all patients who received at least 1 dose of riociguat or who underwent at least 1 session of BPA. All patients who completed the RACE trial continued in a 26-week ancillary follow-up study, during which symptomatic patients with a PVR greater than 320 dyn/s/cm5 showed that they benefited from riociguat as a supplement after BPA or from BPA as a supplement after riociguat treatment.
At 26 weeks, geometric mean PVR decreased to 39.9% (95% CI, 36.2% to 44.0%) of baseline PVR in the BPA arm from 66.7% (95% CI, 60.5% to 73.5%) of baseline PVR in the riociguat arm (ratio of geometric means, 0.60; 95% CI, 0.52-0.69; P <.0001>
Treatment-related serious adverse events (SAEs) were reported in 42% (22 of 52) of patients in the BPA group and 9% (5 of 53) of patients in the riociguat group. The most commonly reported SAEs included lung injury (35% of participants in the BPA arm) and severe hypotension with syncope (4% of patients in the riociguat arm). No treatment-related deaths were reported.
At week 52, a similar decrease in PVR was detected in patients treated with first-line riociguat or first-line BPA (ratio of geometric means, 0.91; 95% CI, 0.79-1 ,04). The incidence of BPA-associated SAEs was lower in patients who received riociguat pretreatment (14% versus 42%, respectively).
Limitations of the current analysis include: the lack of masking due to the comparison of oral therapy with an interventional approach involving the use of invasive procedures repeated over several weeks; sample size smaller than expected due to funding shortfall and study termination before reaching randomization target; exclusion of patients with persistent or recurrent PH after undergoing pulmonary endarterectomy.
“BPA should not be considered as a substitute for medical therapy in patients with inoperable CTEPH, but as a complementary treatment modality to be used in conjunction with medical therapy, particularly when patients present with severe hemodynamic impairment. associated with a higher risk of BPA-induced lung disease injury,” the study authors concluded. “Further studies are needed to explore the effects of sequential treatment with a combination of one or two drugs and BPA in patients with inoperable CTEPH,” they added.
Disclosure: Some of the study authors have disclosed affiliations with biotechnology, pharmaceutical and/or device companies. Please see the original citation for a full list of author disclosures.
Jaïs X, Brenot P, Bouvaist H, et al. Balloon lung angioplasty versus riociguat for the treatment of chronic inoperable thromboembolic pulmonary hypertension (RACE): a multicenter, phase 3, open-label, randomized, controlled trial and an ancillary follow-up study. Respir Med Lancet. Published online August 1, 2022. doi:10.1016/S2213-2600(22)00214-4