Tenecteplase outperforms alteplase in selected stroke patients
MedWire News: Tenecteplase produces better early outcomes than alteplase in patients with stroke who have salvageable brain tissue on computed tomography (CT), show results from a randomized trial.
Tenecteplase is a genetically engineered mutant tissue plasminogen activator, which can be used at a lower dose than alteplase, the standard thrombolytic drug used in stroke patients.
"In addition, because of its different molecular structure, and pharmacodynamic profile, you get more drug into the clot earlier, consequently with more rapid clot lysis," lead researcher Mark Parsons (John Hunter Hospital-Hunter Medical Research Institute, Newcastle, New South Wales, Australia) told MedWire News.
As reported in the New England Journal of Medicine, Parsons and colleagues compared the efficacy of tenecteplase and alteplase in 75 stroke patients. "We 'cherry picked' this group using advanced CT imaging," explained Parsons. "We wanted patients with the most potential to gain from early and effective reperfusion."
All patients had evidence of vessel occlusion on computed tomography (CT) angiography and had a lesion on CT perfusion at least 20% larger than the infarct core, in other words, they had a significant amount of at-risk tissue around a smaller core of permanent damage.
Such patients can have a "Lazarus-like" recovery with prompt recanalization, said Parsons.
Indeed, 64% of the patients randomly assigned to receive tenecteplase (0.10 or 0.25 mg/kg) improved by at least 8 points on the National Institutes of Health Stroke Scale (NIHSS) within 24 hours, compared with 36% of those given alteplase (0.9 mg/kg), which was a significant difference.
The primary imaging endpoint was the percentage of the perfusion lesion that was reperfused at 24 hours, and this was significantly greater in the pooled tenecteplase groups than the alteplase group, at 79.3% versus 55.4%.
Likewise, the primary clinical endpoint of the extent of improvement on the NIHSS at 24 hours was 8 points in the tenecteplase groups versus 3 points in the alteplase group.
Stroke thrombolysis trials commonly assess 3-month outcomes, but Parsons said: "Because this was a phase II study we chose the primary endpoints based on prior work that suggested these were the most sensitive for response to thrombolysis."
And 3-month outcomes were also generally better in the tenecteplase than alteplase groups, with the difference in the proportion of patients with excellent or good functional outcomes (modified Rankin Scale 0-2) achieving significance, at 72% versus 44%.
Safety outcomes did not significantly differ between treatments, but tended to be less common in the tenecteplase than alteplase groups. For example, symptomatic intracranial hematoma occurred in 4% versus 12%, respectively.
The greatest efficacy relative to alteplase occurred with the highest dose of tenecteplase, making this the dose of choice for a larger, phase III trial.
Parsons commented that a phase III study would necessarily involve less highly selected stroke patients, who would benefit less from treatment, whether with tenecteplase or alteplase.
"The challenge is to work out where we should draw the line using advanced CT selection - the balance between generalisabilty versus futile treatment and yet another negative stroke study," he said.
"Our philosophy is that we should more rationally select patients for acute stroke therapy using advanced imaging and not include all comers just so we can generalise the result to all stroke patients. We might discard a very effective treatment if we all include all patients and get a negative result."
MedWire (www.medwire-news.md) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2012
By Eleanor McDermid