ASSENT-1

ASSENT-1 (Assessment of the Safety and Efficacy of a New Thrombolytic) was a phase II randomised, open label, multicentre trial of TNK in AMI. A large cohort of 3235 AMI patients who presented within 12 hours of symptom onset in order to identify an appropriate dose of tenecteplase received a single bolus over 10 seconds for testing in a large mortality trial. 1705 patients received 30 mg, 1457 received 40 mg. Only 73 patients received 50 mg, because this dose was replaced by 40 mg along with reduced-dose heparin protocol when an increased incidence of stroke was observed in the concurrently running TIMI 10B study. It is conceivable that the increased stroke incidence with 50 mg in TIMI 10B was due to chance, as no ASSENT-1 patient receiving 50 mg experienced a stroke and the stroke pattern in ASSENT-1 didn’t display a dose-event relationship.

The graphic shows the major clinical outcomes recorded at 30 days for the total study population. In general, survival rates and net clinical benefit (survival without stroke) were high, especially in patients treated within 6 hours. No striking differences were found between the 30 mg and 40 mg tenecteplase groups with the exception of a higher incidence of reinfarction in the 30 mg group.

The total stroke rate (1.5%) at 30 days was similar to that observed in other trials of thrombolytic therapy, as was the overall safety profile.

There was a non significant trend towards lower rates of intracranial haemorrhage among those patients treated within 6 hours after symptom onset and among those treated after heparin doses were lowered and titration of heparin was started at 6 hours.

ASSENT-1 protocol design

 

ASSENT-1: Major clinical outcomes at 30 days

 

Incidence of stroke at 30 days

 

Subgroup analysis of ICH