CREST-2 reaches a surgical milestone

The Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial (CREST-2) includes two concurrently running two-arm trials assessing intensive medical management (IMM) with or without carotid revascularization for the prevention of stroke.1 One trial tests endarterectomy vs IMM; the other tests stenting vs IMM. Each trial had an original recruitment target of 1240 patients with ≥70% asymptomatic carotid stenosis, randomized 1:1 in each arm. CREST-2 reached an important milestone on September 29, 2023, when the endarterectomy trial achieved its prespecified sample size. This goal was achieved with extensive commitment and adaptations, innovative screening strategies, and despite the COVID-19 pandemic, which at one point suspended new enrollments.2 The National Institute of Neurological Disorders and Stroke (NINDS) provides CREST-2 with direct support and guidance as well as indirect support through access to the central Institutional Review Board of the NINDS StrokeNet clinical trial network. Most surgical trials never achieve their recruitment goals. Of 2542 surgical randomized controlled trials (RCTs) initiated between 2010 and 2014, only 45.9% achieved target enrollment, and only 14.6% achieved target enrollment on time.3 The Stent-Supported Percutaneous-Angioplasty of the Carotid Artery vs Endarterectomy-2 (SPACE-2) was the first sizable RCT with a medical-management group to conclude in more than two decades.4 Unfortunately, SPACE-2 closed enrollment prematurely because of a low enrollment rate, thereby compromising power. SPACE-2 investigators candidly attributed their recruitment challenges to an environment where all hospitals (including academic centers) are "expected to maintain annual performance targets," to "lack of incentives," and to "lack of academic self-awareness."5 The stakes are high in RCTs, because a positive finding may be missed for failure to recruit an adequate number of patients. CREST-2 surgeon investigators demonstrated exceptional dedication by completing enrollment in the endarterectomy trial and deserve credit (Supplementary Material, online only).