The RIGHT-2 trial shows the limitations of a prehospital enrollment model, wrote Karen C. Johnston, MD, professor of neurology at the University of Virginia in Charlottesville, and Valerie L. Durkalski-Mauldin, PhD, professor of medicine at Medical University of South Carolina in Charleston, in an editorial accompanying the RIGHT-2 trial results. The rate of nonstroke diagnoses was so high that it would have reduced the study’s power to assess the efficacy of glyceryl trinitrate (GTN), had the investigators not increased the sample size and changed the statistical analysis plan.

“Future prehospital trials need to consider the implications of enrolling, yet excluding, stroke mimics in the primary analysis,” said Dr. Johnston and Dr. Durkalski-Mauldin. Using telemedicine in the ambulance to facilitate direct contact between the stroke provider and the patient and emergency medical services provider could reduce the enrollment of patients with stroke mimics in clinical trials, they added. “Improved tools to exclude stroke mimics in the field have been difficult to develop and validate. The absence of imaging in most ambulances will continue to limit field personnel from definitively determining ischemic stroke from intracerebral hemorrhage, which will limit hyperacute trials to interventions presumed safe in both populations.”

In addition, the blood pressure reduction that GTN provided might not be clinically relevant, said Dr. Johnston and Dr. Durkalski-Mauldin. “The RIGHT-2 investigators report no difference in blood pressure at day 3 or day 4 of treatment, which might have been related to the very low adherence to study protocol by day 4.

“Regardless of these limitations, RIGHT-2 has provided high-level evidence that GTN given within 4 hours of onset does not significantly improve outcome in hyperacute patients presenting with possible stroke,” the authors concluded (Lancet. 2019 Feb 6. doi: 10.1016/

S0140-6736(19)30276-4). Dr. Johnston and Dr. Durkalski-Mauldin declared no conflicts of interest.