Boehringer Ingelheim terminates phase III study of Metalyse® in out of hospital cardiac arrest

Data analysis shows lack of benefit over placebo

Ingelheim/Germany, 25 July 2006 - Boehringer Ingelheim confirmed today that the TROICA trial, a randomized, double-blind, placebo-controlled Phase III clinical study of the single-bolus thrombolytic Metalyse® (tenecteplase) to assess the efficacy and safety of pre-hospital thrombolytic therapy in cardiac arrest of presumed cardiac origin, had been terminated. The decision was taken on 15 July, following the recommendation of an independent Data Safety Monitoring Board (DSMB).

Enrollment into the trial had been suspended on 23 March following a preliminary data analysis showing that the probability the study would demonstrate superiority of tenecteplase over placebo was very low. Further analysis of the data confirmed that view, and has led to the decision to terminate the trial. The study was not suspended for safety reasons.

With an estimated mortality rate of up to 90%, cardiac arrest is a challenging field for which there is currently no specific approved medication. Early animal and human data suggesting that lytic therapy might prove beneficial had provided the rationale for this exploratory trial.

The decision to terminate the TROICA trial has no implication on the registered indication of Metalyse® for ST elevation acute myocardial infarction.

Further information on the TROICA trial will be communicated at the annual meeting of the European Society of Cardiology/World Congress of Cardiology in September.

About the Study
The TROICA (Thrombolysis In Cardiac Arrest) study enrolled patients suffering from out-of-hospital cardiac arrest of presumed cardiac origin and without restoration of spontaneous circulation (ROSC). The patients received tenecteplase or matching placebo immediately after randomization (= as soon as possible after insertion of the IV line) and after first vasopressor injection within the standardized advanced cardiac life support (ACLS) and cardio pulmonary resuscitation-(CPR) procedures. These procedures were continued until the patients arrive at a cardiac or intensive care unit. The primary endpoint of the trial was the 30-day survival rate and the co-primary endpoint was hospital admission. At the time the trial was suspended, 1,050 of the 1,300 planned patients had been enrolled.

About Tenecteplase
Tenecteplase is a single-bolus thrombolytic agent approved by the European Commission in February 2001 for the treatment of acute myocardial infarction (AMI). Tenecteplase is the first “clot-buster” that can be administered over five seconds in a single bolus dose in the treatment of a heart attack. Tenecteplase is a bioengineered variant of Actilyse® (Alteplase, recombinant), which is a recombinant DNA-derived version of naturally occurring tissue plasminogen activator (t-PA). It is constructed with amino acid substitutions at three sites (the letters T, N and K represent the three regions changed from the natural t-PA protein).

Safety Information
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.

About Cardiac Arrest
Sudden cardiac arrest is a sudden, complete loss of heart function in which little or no blood is being pumped to the rest of the body. Most episodes are caused by the rapid and/ or chaotic activity of the heart known as ventricular tachycardia or fibrillation. Acute myocardial infarction and massive pulmonary embolism are the underlying causes of out-of-hospital cardiac arrest in 50-70% of patients. Unexpected cardiac arrest continues to be an important cause of death in the industrialised world. Unfortunately only a small proportion of out-of-hospital sudden cardiac arrest (SCA) patients survive to hospital discharge.

About Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 143 affiliates in 47 countries and almost 37,500 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.

In 2005, Boehringer Ingelheim posted net sales of 9.5 billion euro while spending almost one fifth of net sales in its largest business segment Prescription Medicines on research and development.

Contact Information

Ute E. Schmidt

Boehringer Ingelheim GmbH

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