ISC 2024 | ZODIAC trial results: conclusive evidence for head positioning in stroke care

So ZODIAC was a study of zero-degree head positioning and large vessel occlusion acute ischemic stroke patients that still had viable brain and therefore were candidates for thrombectomy. This is a question that’s never been answered before. We did not see ZODIAC as a treatment for stroke and I really want to underline that, because there’s others in the past that have tried to do large treatment trials where they looked at outcomes at three months. This is not the case in ZODIAC. We have always seen this as a rescue procedure or a rescue maneuver, if you would, that can salvage brain and hopefully keep it somewhat perfused until patients can get into thrombectomy.

Oftentimes, there’s significant delays to access the procedure. For example, if the patient arrives in a hospital that is not capable of performing thrombectomy, then they require transport and transfer into a larger center. And so we started actually looking at this back in the early 2000s and we have about 20 years of pilot data on this that have shown everything from increased mean flow velocities of 20%, increased blood flow in the brain when you go from 30-degrees down to zero-degrees, clinical improvement in patients, as well as some good safety data that shows that the procedure is safe. And because this is a trial that just looked at whether we could make a difference prior to thrombectomy, large artery occlusion strokes are highly disabled, they’re always kept nil per os and so, therefore, we really weren’t concerned about aspiration, for example. However, we did measure that as a safety outcome. So that is the background to the study.

In terms of methods, we were actually supposed to be enrolling about 182 patients over the five-year period. Of course, we were challenged, as were many other investigators, with Covid. So enrollment was a bit difficult during that time. We also had three planned pre-specified interim analyses. On the second interim analysis, the Data and Safety Monitoring board shut us down for superior efficacy in the zero-degree arm. So the trial was halted on November 1st. But our main outcome, the primary outcome for this study was that patients would have improved clinically on the NIH stroke scale or remained perfectly stable without any fluctuation in the NIH stroke scale if they were at zero-degrees compared to 30-degrees. And we actually found that that was very much the case. In fact, one of every two patients enrolled in the 30-degree arm did have worsening of neurologic function, whereas the patients in the zero-degree arm remained very stable and or improved in that pre-thrombectomy period.

I think that they should. I’ve had some people say, oh, should we do it again in a larger trial? And I have to say that I think it would be a bit unethical actually, to randomize patients to 30-degree heads up, given the fact that the number needed to harm in that group was 1.88. So, again, every other patient deteriorated significantly. And that’s very, very concerning. So I do see this as quite informative to practice. And, you know, on top of our results, I’d like to add that, hey, it’s a free intervention, right? It doesn’t cost us any money to do this and the safety was remarkably good. We actually had no patients with hospital acquired pneumonias using the accepted evidence based definition here in the states. We did see, however, again, the worsening of four or more points in the 30-degree group. So the number needed to harm to worsen four or more points on the NIH stroke scale was 2.48, or round that up to 2.5. So every two and a half patients that you sit up, one is going to worsen four or more points. So again, I think it’s a bit unethical to consider perhaps doing more heads up research in the future. And we also had a significantly higher number of deaths in the 30-degree arm and that was all cause death over a 90 day period. So I do think this should inform practice. Again, it’s simple, doesn’t cost us money and once we know that we have a large vessel occlusion stroke with viable brain, put the head of the bed down.