CHEST-1
Trial question
What is the role of riociguat, a sGC stimulator, in patients with chronic thromboembolic pulmonary hypertension?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
66.0% female
34.0% male
N = 261
261 patients (172 female, 89 male).
Inclusion criteria: patients with inoperable chronic thromboembolic pulmonary hypertension, or persistent or recurrent pulmonary hypertension after pulmonary endarterectomy.
Key exclusion criteria: receipt of an endothelin-receptor antagonist, prostacyclin analog, phosphodiesterase type 5 inhibitor, or nitric oxide donor within the 3 months before study entry.
Interventions
N=173 riociguat (an oral dose of 1-2.5 mg TID for 16 weeks).
N=88 placebo (matching placebo TID for 16 weeks).
Primary outcome
Improvement in 6-minute walk distance at week 16
39 m
-6 m
39.0 m
29.3 m
19.5 m
9.8 m
0.0 m
-9.8 m
Riociguat
Placebo
Significant
increase ▲
Significantly greater improvement in 6-minute walk distance at week 16 (39 m vs. -6 m; MD 46, 95% CI 25 to 67).
Secondary outcomes
Significantly greater decrease of pulmonary vascular resistance at week 16 (-226 dyn•s/cm⁵ vs. 23 dyn•s/cm⁵; MD -246, 95% CI -303 to -190).
No significant difference in reduction in NT-proBNP level at week 16 (291 pg/mL vs. -76 pg/mL; MD 444, 95% CI -45 to 843).
Significant increase in QoL as measured by the EuroQol-5D questionnaire (0.06 vs. -0.08; MD 0.13, 95% CI 0.06 to 0.21).
Safety outcomes
No significant differences in clinical worsening, RV failure, syncope, other adverse events.
Conclusion
In patients with inoperable chronic thromboembolic pulmonary hypertension, or persistent or recurrent pulmonary hypertension after pulmonary endarterectomy, riociguat was superior to placebo with respect to improvement in 6-minute walk distance at week 16.
Reference
Hossein-Ardeschir Ghofrani, Andrea M D'Armini, Friedrich Grimminger et al. Riociguat for the treatment of chronic thromboembolic pulmonary hypertension. N Engl J Med. 2013 Jul 25;369(4):319-29.
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