I’m sure this saturating the medical airwaves this morning, but yesterday’s NEJM published a study which they succinctly summarize on Twitter as “In trial of 75 pts w/ acute ischemic #stroke, tenecteplase assoc w/ better reperfusion, clin outcomes than alteplase.”
Well, that’s very exciting! It’s still smashing a teacup with a sledgehammer, but it does appear to be a more functional sledgehammer. Particularly encouraging were the rates of sustained complete recanalization – which were 36% at 24 hours for alteplase and 58% for tenecteplase – and the rates of intracranial hemorrhage – which were 20% for alteplase and 6% for tenecteplase.
However, the enthusiasm promoted by NEJM, and likely the rest of the internet, should be tempered by the fact that there were only 25 patients in each arm, and there is enough clinical variability between groups that it is not yet practice changing. This was a phase 2B trial, and it is certainly reasonable evidence to proceed with a phase III trial.
Unfortunately, in a replay of prior literature, the authors are all affiliated with Boehringer Ingelheim, the manufacturer of tenecteplase.
“A Randomized Trial of Tenecteplase versus Alteplase for Acute Ischemic Stroke”
http://www.nejm.org/doi/full/10.1056/NEJMoa1109842
Addendum: As Andy Neil appropriately points out, tenecteplase has been studied before – 112 patients over several years, terminated early due to slow enrollment – without seeing a significant advantage.
While I'm conflicted by the ~1hr delay in treatment (vs. noncontrast CT) that CT perfusion studies cause; it seems that they could potentially sort out patients who might benefit most. Though, oddly enough, it appears that the investigators still went ahead and gave alteplase to the majority of patients with negative perfusion studies.
On a side-note, I'm actually surprised (especially with their 6hr treatment window inclusion criteria) that they were able to perform CTP/CTA and treat all but 3 patients in under 4.5hrs.
Regardless, it sounds like the CT perfusion criteria will be dropped for the Phase III trial.
While not statistically significant, I see the 44% proximal MCA occlusion in the alteplase group (vs 28% in pooled TNKase) as a pretty big confounder that they dismissed a bit too lightly.
While I'm conflicted by the ~1hr delay in treatment (vs. noncontrast CT) that CT perfusion studies cause; it seems that they could potentially sort out patients who might benefit most. Though, oddly enough, it appears that the investigators still went ahead and gave alteplase to the majority of patients with negative perfusion studies.
On a side-note, I'm actually surprised (especially with their 6hr treatment window inclusion criteria) that they were able to perform CTP/CTA and treat all but 3 patients in under 4.5hrs.
Regardless, it sounds like the CT perfusion criteria will be dropped for the Phase III trial.
While not statistically significant, I see the 44% proximal MCA occlusion in the alteplase group (vs 28% in pooled TNKase) as a pretty big confounder that they dismissed a bit too lightly.
It's clearly a phase IIB – if you look at their exclusion criteria, they went ahead with "standard treatment" for most, and this is sort of a group that fell out of that. It's not an isolated outcomes improvement – as far back as 2009 they've been looking at TNKase and observing that it results in much better sustained recanalization.
We'll see what Phase III shows – but I'll bet it's just a matter of time until it's finally good riddance to alteplase. Now, if we could just get dabigatran to go away….
It's clearly a phase IIB – if you look at their exclusion criteria, they went ahead with "standard treatment" for most, and this is sort of a group that fell out of that. It's not an isolated outcomes improvement – as far back as 2009 they've been looking at TNKase and observing that it results in much better sustained recanalization.
We'll see what Phase III shows – but I'll bet it's just a matter of time until it's finally good riddance to alteplase. Now, if we could just get dabigatran to go away….