Feasibility of an Ambulance-Based Stroke Trial, and Safety of Glyceryl Trinitrate in Ultra-Acute Stroke

Abstract

Background and Purpose— The practicalities of doing ambulance-based trials where paramedics perform all aspects of a clinical trial involving patients with ultra-acute stroke have not been assessed. Methods— We performed a randomized controlled trial with screening, consent, randomization, and treatment performed by paramedics prior to hospitalization. Patients with probable ultra-acute stroke (<4 hours) and systolic blood pressure (SBP) >140 mm Hg were randomized to transdermal glyceryl trinitrate (GTN; 5 mg/24 hours) or none (blinding under gauze dressing) for 7 days with the first dose given by paramedics. The primary outcome was SBP at 2 hours. Results— Of a planned 80 patients, 41 (25 GTN, 16 no GTN) were enrolled >22 months with median age [interquartile range] 79 [16] years; men 22 (54%); SBP 168 [46]; final diagnosis: stroke 33 (80%) and transient ischemic attack 3 (7%). Time to randomization was 55 [75] minutes. After treatment with GTN versus no GTN, SBP at 2 hours was 153 [31] versus 174 [27] mm Hg, respectively, with difference −18 [30] mm Hg ( P =0.030). GTN improved functional outcome with a shift in the modified Rankin Scale by 1 [3] point ( P =0.040). The rates of death, 4 (16%) versus 6 (38%; P =0.15), and serious adverse events, 14 (56%) versus 10 (63%; P =0.75), did not differ between GTN and no GTN. Conclusions— Paramedics can successfully enroll patients with ultra-acute stroke into an ambulance-based trial. GTN reduces SBP at 2 hours and seems to be safe in ultra-acute stroke. A larger trial is needed to assess whether GTN improves functional outcome. Clinical Trial Registration— URL: http://www.controlled-trials.com/ISRCTN66434824/66434824 . Unique identifier: 66434824.