Thursday 27 August 2015

MR CLEAN: A Randomized Trial of Interventional Stroke therapy (or rescue therapy for highly selected stroke patients after getting tPA)

As a medical community, we are clearly focused on trying to do something to help those with acute ischemic stroke. There is no doubt that this is a common and devastating disease but an effective up ED treatment to benefit the majority of patients has met with failure.

This is not for lack of trying.

Thrombolysis clearly has mixed reviews and is only indicated in a very small percentage of patients. Prior interventional trials published in 2013 were negative. But times change and perhaps technology improves. So along comes Mr Clean.

This was an RCT performed in 16 centres in the Netherlands comparing interventional treatment to “usual care.” But to be clear from the beginning, usual care meant tPA the vast majority of times. Patients were enrolled within 6 hours of onset of symptoms and had to have a proximal clot demonstrated by formal imaging.

90% of all the patients got tPA at a median time of about 90 minutes from stroke onset before they were randomized in to the study. In fact, the median time to randomization was 200 minutes. Therefore this study really was looking at interventional therapy as a rescue option after tPA. Do you think they would have proceeded with interventional therapy if the patient was demonstrating significant early improvement in the ED? Of course not. This was a sicker and highly selected group of patients that did quite poorly in the end.

The primary outcome measure was looking at the odds ratio in an ordinal shift analysis of the modified Rankin score at 90 days. You got that? This type of analysis has been all the rage in the stroke literature recently as it provides some statistical efficiency to find differences. The only challenge is most clinicians have no idea how to interpret this result. How do we translate this outcome measure in to a meaningful one that we can use when engaging in informed decision making? But to be fair, they did report simpler secondary outcome measures.

The results? It seemed to work as in this highly selected patient population in these motivated study centres. The odds ratio for the primary outcome was 1.67 (95% CI 1.21 to 2.30). Who really knows what that means?  There was an absolute difference of 13.5% in the rate of functional independence (mRs 0 to 2) in favour of the intervention 32.6% vs. 19.1%. So, a number needed to treat of about 7.

What should we take home from this? Interventional therapy might work in a few highly selected patients with proximal clots that fail thrombolysis. Of course the patient must present to an experienced centre that provides this high level of service. One might be tempted to extrapolate these results to other patient populations. But caution should certainly be in order as prior studies of less selected patients have not met with positive results. Beware indication creep.

In the end, this really will not help many patients. On average, this study enrolled about 10 patients per year per centre (500 patients over 3 years in 16 centres). Should we be focusing huge amounts of time, effort and money to benefit so few patients? Should we be focusing efforts elsewhere? Who knows?

Berkhemer OA, Fransen PSS, Beumer D, et al. A Randomized Trial of Intraarterial Treatment for Acute Ischemic Stroke. N Engl J Med 2015;372:11-20.

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