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Rationale: Glyceryl trinitrate, a nitric oxide donor, is a candidate treatment for acute stroke; it lowers blood pressure, does not alter cerebral blood flow or platelet function and is neuroprotective in experimental stroke. The ongoing rapid intervention with glyceryl trinitrate in hypertensive stroke trial-2 trial aims to assess the safety and efficacy of paramedic-delivered glyceryl trinitrate in patients with ultra-acute stroke. Aims and design: The rapid intervention with glyceryl trinitrate in hypertensive stroke trial-2 trial is a multicentre UK-based prospective randomised sham-controlled outcome-blinded parallel-group trial in patients with presumed stroke who present to the ambulance service following a 999 emergency call. The primary outcome is the modified Rankin scale measured by central telephone follow-up at 90 days. Results This paper describes the statistical analysis plan for the rapid intervention with glyceryl trinitrate in hypertensive stroke trial-2 trial and was developed prior to unblinding to treatment allocation. The statistical analysis plan includes details of methods for analyses and unpopulated tables and figures to be included in the primary and other secondary publications. Discussion Statistical analysis plan details what analyses will be done prior to unblinding to treatment allocation to avoid bias in the findings. Rapid intervention with glyceryl trinitrate in hypertensive stroke trial-2 trial will determine whether glyceryl trinitrate administered ultra-acutely can improve outcome after stroke. The rapid intervention with glyceryl trinitrate in hypertensive stroke trial-2 trial is registered as ISRCTN26986053.

Stroke represents a global challenge and is a leading cause of permanent disability worldwide. Despite much effort, translation of research findings to clinical benefit has not yet been successful. Failure of neuroprotection trials is considered, in part, due to the low quality of preclinical studies, low level of reproducibility across different laboratories and that stroke co-morbidities have not been fully considered in experimental models. More rigorous testing of new drug candidates in different experimental models of stroke and initiation of preclinical cross-laboratory studies have been suggested as ways to improve translation. However, to our knowledge, no drugs currently in clinical stroke trials have been investigated in preclinical cross-laboratory studies. The cytokine interleukin 1 (IL-1) is a key mediator of neuronal injury and the naturally occurring IL-1 receptor antagonist (IL-1Ra) has been reported as beneficial in experimental studies of stroke. In the present paper, we report on a preclinical cross-laboratory stroke trial designed to investigate the efficacy of IL-1Ra in different research laboratories across Europe. Our results strongly support the therapeutic potential of IL-1Ra in experimental stroke and provide further evidence that IL-1Ra should be evaluated in more extensive clinical stroke trials.

Background: Intravenous thrombolysis is one of few evidence-based treatments for acute stroke. Treatment uptake is low outside major stroke care centres. There is a need for greater understanding of barriers encountered by clinicians when seeking to increase thrombolysis rates. Aim: The aim of this study is to describe physicians’ and nurses’ perceptions regarding thrombolysis for acute stroke at hospitals in the earlier stages of thrombolysis implementation. Methods: A cross-sectional paper survey completed by physicians’ and nurses’ was distributed to 1127 staff at stroke care units, emergency departments or equivalent stroke care facilities at 19 Australian hospitals, as part of a cluster randomised controlled trial for thrombolysis implementation and systems improvement. Results: Of 1127 potential participants, 503 (148 physicians and 355 nurses) completed surveys (45% response rate). Over 90% agreed that thrombolysis improved the odds of independent survival. However, 42% to 58% agreed that there were limitations in the evidence base. A small proportion of staff indicated deficits in technical competencies. Interactive or competency-based training was reported by less than two-thirds of the sample. Challenges such as quick bed availability were identified. Emergency department physicians were less positive towards the treatment compared with nurses (p Conclusion: Australian hospitals seeking to address barriers to stroke thrombolysis implementation may benefit from the availability of interactive and competency-based training, staff performance feedback, support to make beds available quickly and bypass arrangements to quickly deliver acute stroke patients to appropriate facilities.