Randomized clinical trials provide the most reliable evidence to guide the management of stroke and threatened stroke and reflect the interests of the stroke research community. The spectrum of phase III randomized clinical trials in stroke has not been previously characterized.
Phase III stroke randomized clinical trials published between 2012 and 2014 were identified by search of the Cochrane Central Register of Controlled Trials supplemented by recent publications known to the co-authors.
Thirty-four randomized clinical trials were included involving 85 770 participants: 20 acute stroke randomized clinical trials (32 590 patients), 11 stroke prevention randomized clinical trials (28 964 patients), and three randomized clinical trials in which stroke was a major component of a composite primary outcome involving nonstroke patients (24 216 patients). Twenty-two (65%) trials were international, and eight (24%) were industry sponsored. Drugs were tested in 21 (62%) randomized clinical trials, with devices ( n = 9), surgery ( n = 3), and diet ( n = 1) in the remainder. Thirteen (38%) randomized clinical trials were stopped early: seven for futility, three for efficacy, two for harm, and one for budget/administrative reasons. Overall, the results of seven (21%) randomized clinical trials were positive, five (15%) equivocal, 18 (53%) negative, and four (12%) inconclusive. Considering positive and definitively negative randomized clinical trials testing currently used interventions, 11 (32%) randomized clinical trials have direct implications for clinical management.
The diversity of interventions, high-quality, and worldwide origins of recently published phase III randomized clinical trials reflects a vibrant international stroke research community. The current generation of stroke randomized clinical trials provides important guidance for stroke prevention and acute stroke care.