These study subjects were randomly assigned to receive high-dose riociguat capped at 2.5 mg three times daily (254 patients), low-dose riociguat capped at 1.5 mg three times daily (63 patients), or placebo (126 patients) for 12 weeks. The analysis of data from the low-dose group was considered exploratory and was reported separately.
The primary endpoint – change from baseline in 6-minute walk distance – increased by a mean of 30 m in the high-dose group but decreased by a mean of 6 m in the placebo group in the intention-to-treat analysis. The results were similar in the per-protocol analysis, the investigators reported (N. Engl. J. Med. 2013 July 25 [doi: 10.1056/NEJMoa1209655]).
This treatment benefit was consistent across several subgroups of patients. In addition, the active drug significantly decreased pulmonary vascular resistance, improved mean pulmonary artery pressure and cardiac output, lengthened the interval to clinical worsening, improved NT-proBNP levels, improved WHO functional class, and improved scores on the Borg dyspnea scale.
In exploratory analyses, riociguat did not improve scores on one measure of QOL but did so on a disease-specific QOL tool.
Drug-related serious adverse events occurred in 1.4 % of patients receiving high-dose riociguat and 1% of those receiving placebo. A total of 3% of patients in the riociguat group and 7% of those in the placebo group discontinued the study drug because of adverse events.
Serious or drug-related adverse events in both groups included increased hepatic enzyme levels, acute renal failure, syncope, esophageal pain and swelling, supraventricular tachycardia, hypotension, generalized edema, hypoxemia, dyspnea, and worsening of pulmonary hypertension. There were two deaths in the riociguat group and three in the placebo group, none of which were considered to be related to the study drug.
A total of 396 of the subjects in the PATENT-1 study elected to enroll in an extended study of the long-term safety and efficacy of riociguat (the PATENT-2 clinical trial). An exploratory analysis of data from the first 12 weeks of that study showed a further mean increase of 53 m in 6-minute walk distance with high-dose riociguat.
CHEST-1 and PATENT-1 were funded by Bayer HealthCare. Dr. Ghofrani reported ties to Actelion, Bayer, and other companies. His associates reported ties to numerous industry sources.