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.
Journal
The Lancet. Respiratory medicine
ISSN: 2213-2619
Titre abrégé: Lancet Respir Med
Pays: England
ID NLM: 101605555
Informations de publication
Date de publication:
Oct 2022
Oct 2022
Historique:
received:
23
01
2022
revised:
12
05
2022
accepted:
19
05
2022
pubmed:
5
8
2022
medline:
5
10
2022
entrez:
4
8
2022
Statut:
ppublish
Résumé
Riociguat and balloon pulmonary angioplasty (BPA) are treatment options for inoperable chronic thromboembolic pulmonary hypertension (CTEPH). However, randomised controlled trials comparing these treatments are lacking. We aimed to evaluate the efficacy and safety of BPA versus riociguat in patients with inoperable CTEPH. In this phase 3, multicentre, open-label, parallel-group, randomised controlled trial done in 23 French centres of expertise for pulmonary hypertension, we enrolled treatment-naive patients aged 18-80 years with newly diagnosed, inoperable CTEPH and pulmonary vascular resistance of more than 320 dyn·s/cm Between Jan 19, 2016, and Jan 18, 2019, 105 patients were randomly assigned to riociguat (n=53) or BPA (n=52). At week 26, the geometric mean pulmonary vascular resistance decreased to 39·9% (95% CI 36·2-44·0) of baseline pulmonary vascular resistance in the BPA group and 66·7% (60·5-73·5) of baseline pulmonary vascular resistance in the riociguat group (ratio of geometric means 0·60, 95% CI 0·52-0·69; p<0·0001). Treatment-related serious adverse events occurred in 22 (42%) of 52 patients in the BPA group and five (9%) of 53 patients in the riociguat group. The most frequent treatment-related serious adverse events were lung injury (18 [35%] of 52 patients) in the BPA group and severe hypotension with syncope (two [4%] of 53 patients) in the riociguat group. There were no treatment-related deaths. At week 52, a similar reduction in pulmonary vascular resistance was observed 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-related serious adverse events was lower in patients who were pretreated with riociguat (five [14%] of 36 patients vs 22 [42%] of 52 patients). At week 26, pulmonary vascular resistance reduction was more pronounced with BPA than with riociguat, but treatment-related serious adverse events were more common with BPA. The finding of fewer BPA-related serious adverse events among patients who were pretreated with riociguat in the follow-up study compared with those who received BPA as first-line treatment points to the potential benefits of a multimodality approach to treatment in patients with inoperable CTEPH. Further studies are needed to explore the effects of sequential treatment combining one or two medications and BPA in patients with inoperable CTEPH. Programme Hospitalier de Recherche Clinique of the French Ministry of Health and Bayer HealthCare. For the French translation of the abstract see Supplementary Materials section.
Sections du résumé
BACKGROUND
Riociguat and balloon pulmonary angioplasty (BPA) are treatment options for inoperable chronic thromboembolic pulmonary hypertension (CTEPH). However, randomised controlled trials comparing these treatments are lacking. We aimed to evaluate the efficacy and safety of BPA versus riociguat in patients with inoperable CTEPH.
METHODS
In this phase 3, multicentre, open-label, parallel-group, randomised controlled trial done in 23 French centres of expertise for pulmonary hypertension, we enrolled treatment-naive patients aged 18-80 years with newly diagnosed, inoperable CTEPH and pulmonary vascular resistance of more than 320 dyn·s/cm
FINDINGS
Between Jan 19, 2016, and Jan 18, 2019, 105 patients were randomly assigned to riociguat (n=53) or BPA (n=52). At week 26, the geometric mean pulmonary vascular resistance decreased to 39·9% (95% CI 36·2-44·0) of baseline pulmonary vascular resistance in the BPA group and 66·7% (60·5-73·5) of baseline pulmonary vascular resistance in the riociguat group (ratio of geometric means 0·60, 95% CI 0·52-0·69; p<0·0001). Treatment-related serious adverse events occurred in 22 (42%) of 52 patients in the BPA group and five (9%) of 53 patients in the riociguat group. The most frequent treatment-related serious adverse events were lung injury (18 [35%] of 52 patients) in the BPA group and severe hypotension with syncope (two [4%] of 53 patients) in the riociguat group. There were no treatment-related deaths. At week 52, a similar reduction in pulmonary vascular resistance was observed 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-related serious adverse events was lower in patients who were pretreated with riociguat (five [14%] of 36 patients vs 22 [42%] of 52 patients).
INTERPRETATION
At week 26, pulmonary vascular resistance reduction was more pronounced with BPA than with riociguat, but treatment-related serious adverse events were more common with BPA. The finding of fewer BPA-related serious adverse events among patients who were pretreated with riociguat in the follow-up study compared with those who received BPA as first-line treatment points to the potential benefits of a multimodality approach to treatment in patients with inoperable CTEPH. Further studies are needed to explore the effects of sequential treatment combining one or two medications and BPA in patients with inoperable CTEPH.
FUNDING
Programme Hospitalier de Recherche Clinique of the French Ministry of Health and Bayer HealthCare.
TRANSLATION
For the French translation of the abstract see Supplementary Materials section.
Identifiants
pubmed: 35926542
pii: S2213-2600(22)00214-4
doi: 10.1016/S2213-2600(22)00214-4
pii:
doi:
Substances chimiques
Pyrazoles
0
Pyrimidines
0
riociguat
RU3FE2Y4XI
Banques de données
ClinicalTrials.gov
['NCT02634203']
Types de publication
Clinical Trial, Phase III
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
961-971Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2022 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests XJ, PB, HB, MJ, LS, OS, FP, CP, LG, EF, DM, MH, and GS report grants from the French Ministry of Health and Bayer HealthCare, during the conduct of the study. XJ reports grants from Acceleron, Janssen, and Merck Sharp & Dohme (MSD); personal fees from Janssen and MSD; and non-financial support from Janssen, outside of this study. MC reports personal fees from Menarini, and non-financial support from France Oxygène and Actelion, outside of this study. AC reports grants from Actelion and GlaxoSmithKline; personal fees from MSD, Chiesi, and GlaxoSmithKline; and non-financial support from Asten Santé, Johnson & Johnson, Chiesi, and Boehringer Ingelheim, outside of this study. VC reports grants from Boehringer Ingelheim; personal fees from Boehringer Ingelheim, Roche, Galapagos, Galecto, Shionogi, Fibrogen, RedX, Promedior, Celgene, Bristol Myers Squibb, and PureTech; and non-financial support from Boehringer Ingelheim and Roche, outside of this study. PDG reports personal fees from Bayer HealthCare and MSD, outside of this study. LS reports grants from Janssen, MSD, and GlaxoSmithKline; personal fees from Janssen and MSD; and non-financial support from Janssen, outside of this study. OS reports grants from GlaxoSmithKline, Acceleron, Janssen, and MSD; and personal fees from Gossamer Bio, Janssen, AOP Orphan, Ferrer, Acceleron, and MSD, outside of this study. FP reports grants from Acceleron, MSD, and Janssen; personal fees from MSD and Bayer HealthCare; and non-financial support from Bayer HealthCare, outside of this study. CT reports personal fees from Bayer HealthCare, Janssen, and GlaxoSmithKline; and non-financial support from Orkyn and Bayer HealthCare, outside of this study. EF reports personal fees from MSD, outside of this study. DM reports grants from Acceleron, Janssen, and MSD; and personal fees from Acceleron, Bayer HealthCare, Janssen, and MSD, outside of this study. MH reports grants from the French National Research Agency, Acceleron, Janssen, and MSD; and personal fees from Acceleron, Janssen, MSD, and United Therapeutics, outside of this study. GS reports personal fees from Acceleron, Janssen, MSD, and Bayer HealthCare, outside of this study. All other authors declare no competing interests.