Boehringer Ingelheim and Genentech, Inc., announced that they plan to test the single-bolus thrombolytic TNKase/Metalyse (Tenecteplase) in combination with percutaneous coronary intervention (PCI, also known as primary angioplasty) as a potential treatment regimen for acute myocardial infarction (AMI).

The 4,000-patient trial, ASSENT 4 PCI (Assessment of the Safety and Efficacy of a New Treatment Strategy for Acute Myocardial Infarction) has two arms: half the patients enrolled will receive a drug regimen consisting of a full-dose, single bolus of TNKase/Metalyse plus unfractionated heparin followed by immediate PCI. The other 50 per cent of patients will receive immediate PCI alone.

The study will be carried out at approximately 350 enrolling sites internationally. Its purpose is to investigate whether patients who arrive at the catheterization laboratory with a fully or partially opened artery as a result of lytic therapy have better outcomes than those who do not receive the lytic regimen before PCI. The primary endpoint of ASSENT 4 PCI is a composite of death or cardiogenic shock or congestive heart failure within 90 days.

"Until now, clinicians treating heart attack patients have tended to choose either a thrombolytic agent or PCI," observed prof. Frans Van de Werf, University Hospital Gasthuisberg, Leuven, Belgium, and chairman of the ASSENT 4 PCI trial. "However, the two therapeutic modalities may prove to be complementary. It is our goal to determine whether patients who undergo PCI with an artery that is already opened [via thrombolysis] can be discharged from the hospital with a smaller infarct and better left ventricular function and a more favorable clinical outcome," prof. Van de Werf added.

The rationale of the trial was further explained by trial co-chairman Allan M. Ross, MD, George Washington University, Washington, DC "PCI is a fine treatment modality - when performed within 60 to 90 minutes of the patient's arrival at hospital. But few hospitals around the world can perform PCI within that time period on a 24-hour-a-day, 7-day-a-week basis. This means that many patients may not derive the full benefit of the intervention. In ASSENT 4 PCI, we are examining whether AMI patients facing a delay prior to PCI may be better served by receiving a bolus thrombolytic plus heparin, which can be given immediately, followed by PCI when it becomes possible," said Dr. Ross.

Time is muscle when treating AMI. When a blood clot in an artery nearly or completely stops blood flow to the heart, cells in the heart muscle begin to die. The sooner patients receive treatment, the sooner blood flow can be restored, often saving a life or significantly decreasing irreversible damage to the muscle.

ASSENT 4 PCI will enroll patients for whom PCI is the planned therapeutic option but only where patients expected arrival to the catheterization lab is longer than 60 minutes and less than 3 hours, either because the hospital is not capable of immediately mobilizing the PCI team and gaining access to the catheterization lab, or because patient transfer is required in order to provide PCI. The ASSENT 4 PCI trial is expected to enroll the first patient within the next month.

TNKase/Metalyse (Tenecteplase) is the only thrombolytic that can be administered over five seconds in a single dose, offering physicians the fastest administration of a thrombolytic to date in the treatment of heart attack. Tenecteplase works by stimulating the body's own clot-dissolving mechanism by activating plasminogen, a naturally occurring substance secreted by endothelial cells in response to injury to the artery walls that contributes to clot formation. When Tenecteplase activates plasminogen, it converts into plasmin, which breaks down the fibrin mesh that binds the clot together. The clot is then dissolved, restoring blood flow to the heart.

All thrombolytic agents increase the risk of bleeding, including intracranial bleeding, and should be used only in eligible patients. In addition, thrombolytic therapy increases the risk of stroke, including hemorrhagic stroke, in elderly patients.

Genentech markets Tenecteplase (TNKase) in the United States. Boehringer Ingelheim markets Tenecteplase worldwide, with the exception of the U.S., Canada, and Japan, under the trade name Metalyse.