Nancy A. Melville

October 27, 2014

BALTIMORE, Maryland — The use of intravenous thrombolysis in the treatment of stroke in patients who wake up with symptoms and therefore cannot identify the time of onset appears safe and feasible, preliminary findings suggest.

Patients with "wake-up stroke" — representing as many as 15% to 25% of all strokes — typically do not qualify for acute thrombolytic treatment because of the simple inability to know when the symptoms truly started.

"Many neurologists have had the frustrating experience of having a patient that meets all criteria for IV tPA [intravenous tissue plasminogen activator] but cannot be treated because they woke up with symptoms," lead author Victor C. Urrutia, MD, director of the Comprehensive Stroke Center at The Johns Hopkins Hospital in Baltimore, Maryland, told Medscape Medical News.

A previous trial, Abciximab in Emergency Stroke Treatment Trial-II (AbESTT), that investigated use of abciximab to treat stroke in wake-up patients, showed higher rates of bleeding that actually halted the trial, as well as poorer outcomes. However, various subsequent studies have shown that treatment of wake-up stroke did not increase the risk for hemorrhage. Furthermore, Dr Urrutia speculates that stroke symptoms in fact likely usually begin close to the time of awakening.

"My hypothesis is that wake-up stroke patients most likely have a time of onset [of] when they wake up with stroke symptoms or within a brief timeframe from waking up," he said.

"This is supported by the imaging studies and circadian rhythm studies and the comparison with patients that meet criteria for tPA," he added. "Therefore, treatment with IV tPA should be safe and effective, if done within the accepted time window and meeting all other criteria for standard treatment."

Preliminary findings from the Safety of Intravenous ThromboLytics in Stroke ON Awakening (SAIL-ON) trial, were presented here at the American Neurological Association (ANA) 2014 Annual Meeting. The study was funded by Genentech.


Dr Urrutia and his colleagues presented preliminary data on treatment within 4.5 hours of waking up for the first 10 of a planned 20 patients with wake-up stroke.

The open-label study has a primary outcome of symptomatic intracerebral hemorrhage (ICH) within the first 36 hours of standard IV tPA treatment, using noncontrast computed tomography as the brain imaging modality.

Secondary outcomes include measures of stroke impairment, including National Institutes of Health Stroke Scale (NIHSS) score at 24 hours and function at 90 days.

Patients had a mean age of 66 and average NIHSS score of 7 (range, 4 to 11). The average amount of time from wake-up to the administration of IV tPA was 194.4 minutes (range, 120 to 270 minutes), and the average period from the last time the patient was seen to be normal to the administration of IV tPA was 589.7 minutes (range, 360 to 870 minutes).

At 90-day follow-up, the patients had a mean modified Rankin scale score of 1 (range, 0 to 5) and no patient had a symptomatic intracerebral hemorrhage in the first 36 hours. One patient had an asymptomatic ICH.

Dr Urrutia noted that the number of patients in the study is currently up to 14 and there have still been no reports of symptomatic ICH.

"[The results] are reassuring, and align well with the background data that supports our hypothesis," Dr Urrutia said.

In addition to some retrospective studies also suggesting no increases in symptomatic ICH with wake-up stroke, several studies have shown, through imaging of patients with a known time of onset in wake-up stroke, circadian variations associated with symptom onset (Todo et al, 2006; Huisa et al, 2010).

Research is meanwhile continuing, with several other prospective clinical trials looking at various approaches to wake-up stroke, all motivated by the potential benefits to patients, Dr Urrutia said.

"If treatment with IV tPA is proven to be safe and effective in wake up strokes, it would bring significant benefit by expanding the patients that can be treated," he said.

"Currently, it is estimated that only 4% of all strokes are treated with IV tPA. If wake-up stroke patients could be treated, the impact would be significant."

The study was supported by Genentech. Dr Urrutia has disclosed no relevant financial relationships.

American Neurological Association (ANA) 2014 Annual Meeting. Abstract M1224. Presented October 13, 2014


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