{"id":42178,"date":"2014-03-17T15:25:40","date_gmt":"2014-03-17T19:25:40","guid":{"rendered":"http:\/\/blogs.nejm.org\/cardioexchange\/?post_type=news&p=42178"},"modified":"2014-03-17T15:25:40","modified_gmt":"2014-03-17T19:25:40","slug":"phase-4-actelion-study-misses-primary-endpoint","status":"publish","type":"post","link":"https:\/\/blogs.nejm.org\/cardioexchange\/2014\/03\/17\/phase-4-actelion-study-misses-primary-endpoint\/","title":{"rendered":"Phase 4 Actelion Study Misses Primary Endpoint"},"content":{"rendered":"

Actelion\u00a0announced<\/a>\u00a0today that a phase 4 study with its blockbuster drug bosentan (Tracleer) had failed to meet its primary endpoint.<\/p>\n

The\u00a0COMPASS-2<\/a>\u00a0trial was a\u00a0prospective, randomized, double-blind, placebo-controlled trial\u00a0evaluating the effect of bosentan on the time to first confirmed event in patients with symptomatic pulmonary arterial hypertension (PAH) already receiving treatment with sildenafil.<\/p>\n

According to the company, a 17% risk reduction in the primary endpoint of the time to first event did not reach statistical significance (p=0.25).\u00a0Actelion\u00a0reported that an exploratory analysis showed a significant increase in the 6-minute walking distance in the combination group and “and\u00a0a placebo-corrected incidence of 15.4%” in elevated liver enzymes over 23 months of treatment.<\/p>\n

\n

The press release quoted the University of Michigan’s Vallerie McLaughlin, chair of the trial’s steering committee: “While the observed risk reduction of 17% did not reach statistical significance, I am convinced that this study provides important information for the scientific community and we are committed to perform all the necessary analyses to fully understand the outcome of the study.”<\/p>\n

The company said that the full results of the study will be presented at future congresses and in peer-reviewed publications.<\/p>\n

John Ryan, a pulmonary hypertension expert at the\u00a0University of Utah, offered the following perspective:<\/p>\n

\n

“The COMPASS-2 trial assessed the efficacy of a common\u00a0clinical practice, namely the addition of bosentan (an endothelia receptor\u00a0antagonist, ERA) to patients with pulmonary arterial hypertension (PAH)\u00a0already\u00a0taking sildenafil (phosphodiesterase 5 inhibitor, PDE5i). The safety and\u00a0benefit\u00a0(or otherwise) of this combination therapy has been largely unknown. But\u00a0because\u00a0this disease process can advance so rapidly with a limited life\u00a0expectancy, if\u00a0patients are deemed to be failing monotherapy with clinical deterioration,\u00a0most\u00a0PAH providers are aggressive in adding on a second agent. Therefore the\u00a0COMPASS-2 trial represents a marked advance in our knowledge of the merits\u00a0of\u00a0dual therapy. Looking forward, it will be important to perform similar\u00a0combination trials with the other classes of agents available, especially\u00a0ERAs\u00a0and the new soluble guanylate cyclase stimulators (riociguat being the\u00a0only currently\u00a0available agent).”<\/p>\n<\/blockquote>\n

\n<\/div>\n","protected":false},"excerpt":{"rendered":"

Actelion\u00a0announced\u00a0today that a phase 4 study with its blockbuster drug bosentan (Tracleer) had failed to meet its primary endpoint. The\u00a0COMPASS-2\u00a0trial was a\u00a0prospective, randomized, double-blind, placebo-controlled trial\u00a0evaluating the effect of bosentan on the time to first confirmed event in patients with symptomatic pulmonary arterial hypertension (PAH) already receiving treatment with sildenafil. According to the company, a […]<\/p>\n","protected":false},"author":196,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1,14,7],"tags":[1776,2027,1744,1787],"class_list":["post-42178","post","type-post","status-publish","format-standard","hentry","category-general","category-heart-failure","category-prevention","tag-actelion","tag-bosentan","tag-pulmonary-arterial-hypertension","tag-pulmonary-hypertension"],"_links":{"self":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/posts\/42178","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/users\/196"}],"replies":[{"embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/comments?post=42178"}],"version-history":[{"count":0,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/posts\/42178\/revisions"}],"wp:attachment":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/media?parent=42178"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/categories?post=42178"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/tags?post=42178"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}