February 14, 2007 (San Francisco) — A new pilot study shows that getting acute stroke patients out of bed and engaging them in exercise therapy within 24 hours of symptom onset is a feasible and safe form of rehabilitation.

The results of A Very Early Rehabilitation Trial (AVERT), a single-blind, randomized controlled trial, presented here at the American Stroke Association International Conference on Stroke 2007, showed an absolute 9% difference in outcomes in stroke patients who engaged in early, intensive rehabilitation compared with those who did not.

"At this point, all we can say from these results is that there was a 9% trend toward benefit. Nonetheless, this is encouraging and warrants a larger trial to determine efficacy," principal investigator Julie Bernhardt, PhD, from the University of Melbourne, Australia, told Medscape.

"We believe early intensive exercise therapy has the potential to reduce the burden of stroke and offer hope to the 80% of patients who are not suitable candidates for or who do not have access to clot-busting drugs," she added.

Danger Concern?

According to Dr. Bernhardt, very early mobilization (VEM), with an emphasis on mobility training, has not been tested before in high-quality clinical trials. This is likely due to concern among neurologists and other healthcare providers that it may be dangerous.

"There is indirect evidence that if we move rehabilitation into the very early time period there can be positive benefit for stroke patients. But what we don't really have a clear picture of is whether very early rehabilitation is safe, feasible, or effective," she said.

To test their hypothesis that a very early rehabilitation protocol emphasizing early mobilization was both safe and feasible, the investigators randomized 71 acute stroke patients. Of these, 38 individuals received VEM and 33 received standard care. Patients were treated for 14 days or until discharge, whichever was shorter.

Inclusion criteria were broad, said Dr. Bernhardt, including all individuals older than 18 years with confirmed stroke, either first or recurrent, admitted to the hospital within 24 hours of symptom onset.

Lost Opportunity

Exclusion criteria included moderate and severe premorbid disability or patients who were too ill with other conditions or with stroke to be able to participate. However, she added, the major reason for exclusion was that patients did not get to the hospital within the 24-hour time frame.

Patients were well matched according to age, sex, first stroke status, and type of stroke. Those randomized to VEM received their first intervention within 24 hours of stroke symptom onset, which was delivered by a nurse and physical therapist team. The intervention continued for 14 days or until discharge, whichever was shorter.

Although the investigators aimed to recruit equal numbers of patients across the stroke severity spectrum, they were not able to achieve this. However, Dr. Bernhardt pointed out that more than 55% of patients included in the study had moderate to severe stroke.

The study's primary safety outcome was death at 3 months following stroke, and the feasibility end point was the total dose of mobilization that could be delivered.

Secondary outcomes included serious adverse events at 14 days. "We were particularly interested in looking at fall rates and whether or not patients experienced any significant drop in blood pressure that may have prevented them from participating," said Dr. Bernhardt.

In addition, patients were asked about the perceived exertion after each intervention.

Excessive Exertion

At 3-month follow-up, there were 3 deaths in the standard-care group and 8 in the early-intervention group, a risk difference of 12% and an overall death rate of 15.5%. However, said Dr. Bernhardt, it is important to point out that those who died were older — between age 65 and 92 — and had a median National Institutes of Health Stroke Score of 22.

"These patients were at the severe end of the stroke spectrum, 8 of them had a total anterior circulatory infarct, so they were pretty ill, older, and generally a much more severely affected group," she said.

Dr. Bernhardt added that the low death rate in the standard-care group was something of an anomaly and added that the overall death rate of 15.5% is in line with research from the Northeast Melbourne Stroke Incidence Study Data of hospitalized stroke patients, where the overall death rate was 23.1%.

Secondary outcomes were similar between the 2 groups. In the standard-care group, the fall rate was 22.8%, vs 19.7% for the VEM group. None of the patients in either group was unable to mobilize due to a drop in blood pressure.

Interestingly, said Dr. Bernhardt, even though patients in the VEM group received twice as much therapy as the standard-care individuals, their perception of excessive exertion was 8.2%, vs 10.4% for their counterparts who received standard care.

Largest-Ever Rehab Trial

The next phase of AVERT, said Dr. Bernhardt, is a large multicenter randomized clinical trial that will include more than 2000 patients at more than 10 centers across Australia and possibly Europe and North America.

The trial, which will conclude in 2010, will be the largest-ever stroke rehabilitation trial and will look at efficacy and the cost-effectiveness of what Dr. Bernhardt said is "a practical and simple intervention."

"Clinical trials to test these types of rehabilitation interventions are urgently needed. We hope to prove that early intensive exercise therapy should be a routine part of early stroke care for the 700,000 patients who will have a stroke within the next year," she said.

International Stroke Conference 2007: Abstract 86.