by Martha Kerr

Tenecteplase (TNK), a new, modified form of tissue plasminogen activator (tPA), is faster, more effective, safer and easier to administer than alteplase (Activase, Genentech Inc., South San Francisco, CA), the only currently approved form of tPA.

Those findings come from the Spanish TNK-TPA Reperfusion Stroke Study, and were presented by Dr. Carlos A. Molina of Hospital Vall d'Hebron in Barcelona during the American Stroke Association's International Stroke Conference 2008.

The study involved 122 consecutive patients with acute ischemic strokes due to middle cerebral artery (MCA) occlusion and eligible for thrombolytic therapy. All patients had a diffusion-weighted/perfusion-weighted (DWI/PWI) MRI mismatch of more than 20 per cent of the DWI lesion, indicating a large area of ischemia surrounding the infarcted penumbra of the lesion.

Patients were randomized to a 0.4 mg/kg bolus of tenecteplase or standard tPA (0.9 mg/kg, with the first ten per cent given as a bolus and the remainder in a one-hour infusion). One-third of patients received tenecteplase and two-thirds received standard tPA.

Complete recanalization at two hours occurred in 42.4 per cent of the tenecteplase group and in 33.4 per cent of standard tPA-treated patients. Some degree of MCA recanalization at two hours took place in 69 per cent of the tenecteplase group and 53 per cent of the standard tPA group.

The beginning of recanalization occurred at 19 minutes in the tenecteplase group and 24 minutes with standard tPA, which was not a statistical difference. However, the difference in recanalization rates at two hours did reach statistical significance.

"There is a modest advantage (with tenecteplase) over standard tPA in opening blood vessels," Dr. Molina told Reuters Health.

Asymptomatic intracranial hemorrhage was seen on CT at 24-36 hours in 28 per cent and 21 per cent of the tenecteplase and alteplase groups, respectively.

NIHSS scores at 24 hours had improved by more than four points in 63 per cent of the tenecteplase-treated patients and in 51 per cent of alteplase-treated patients. Clinical recovery was 2.5-fold greater with the newer modified form of tPA than standard tPA.

Functional independence at three months occurred in 66 per cent of tenecteplase-treated and 52 per cent of standard tPA-treated patients, Dr. Molina reported.

Tenecteplase has a longer half-life and it is easier to administer than standard tPA, the Spanish investigator noted. These phase 2 results "merit direct, randomized phase 3 trials," Dr. Molina said.


Source: Reuters