Tenecteplase in other conditions*

The Pulmonary EmbolIsm THrOmbolysis (PEITHO) study is a collaborative effort of physicians involved in the treatment of patients suffering from acute pulmonary embolism. It was initiated and is sponsored (as an Investigator-Initiated Study) by the Clinical Research Delegation at Assistance Publique-Hôpitaux de Paris (AP-HP), which is a non-profit organisation.

The primary objective of the PEITHO study is to demonstrate the clinical benefits of thrombolysis with tenecteplase over placebo in normotensive patients with acute pulmonary embolism and right ventricular dysfunction.

The secondary objective is to assess the safety after administration of tenecteplase in normotensive patients with acute pulmonary embolism and with echocardiographic and laboratory evidence of right ventricular dysfunction.

Study design

The PEITHO study is a prospective, randomised, double-blind, placebo-controlled, international, multi-centre, parallel-group comparison trial evaluating the efficacy and safety of single IV bolus tenecteplase plus standard anticoagulation therapy compared with standard anticoagulation therapy in normotensive patients with acute pulmonary embolism and right ventricular dysfunction, based on echocardiographic and laboratory evidence.

The primary endpoint is a composite of all-cause mortality or haemodynamic collapse within 7 days of randomisation.

Secondary endpoints include death within 7 days, haemodynamic collapse within 7 days, confirmed symptomatic pulmonary embolism recurrence within 7 days, and death within 30 days.

Approximately 1000 patients were enrolled between 2007 and 2012.

Results can be found in Meyer G, et al. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med. 2014 Apr 10;370(15):1402-1411.

PEITHO: Study design

PEITHO  Study  design  PEITHO study included haemodynamically stable patients with PE randomised into either placebo or tenecteplase treatment arm.

References:

  1. The PEITHO Steering Committee. Single-bolus tenecteplase plus heparin compared with heparin alone for normotensive patients with acute pulmonary embolism who have evidence of right ventricular dysfunction and myocardial injury: rationale and design of the Pulmonary Embolism Thrombolysis (PEITHO) trial. Am Heart J 2012;163:33-38(e31).

Approximately 70% of people that have an out-of-hospital cardiac arrest have underlying acute myocardial infarction or pulmonary embolism. Therefore, thrombolysis during cardiopulmonary resuscitation may improve survival.

The Thrombolysis in Cardiac Arrest (TROICA) trial was a prospective double-blind, randomised, placebo-controlled trial in 66 European emergency medical-service systems that compared thrombolysis with tenecteplase with placebo during cardiopulmonary resuscitation.

Study design

The TROICA study randomly assigned 1,050 adult patients with witnessed out-of-hospital cardiac arrest of presumed cardiac origin and with initiation of basic or advanced life support within 10 minutes after collapse, to receive tenecteplase or placebo during cardiopulmonary resuscitation. Adjunctive heparin or aspirin was not used.

The primary endpoint was survival at 30 days.

Secondary endpoints included hospital admission, return of spontaneous circulation, 24-h survival, survival to hospital discharge, and neurologic outcome of surviving patients.

Results

After a blinded review of data from the first 443 patients, the TROICA Data and Safety Monitoring Board recommended discontinuation of enrolment of asystolic patients because of low survival. The trial was stopped prematurely for futility after 1,050 patients had been enrolled.

The 30-day clinical outcomes do not support use of tenecteplase over placebo for patients with out-of-hospital cardiac arrest. There was no significant difference in the primary endpoint of 30-day survival between the tenecteplase and placebo groups (14.7% versus 17.0%; p=0.36; relative risk 0.87; 95% confidence interval [CI] 0.65 to 1.15). Similarly, there were no significant differences in any of the secondary endpoints between groups. There were more intracranial haemorrhages in the tenecteplase group (2.7% versus 0.4%; p=0.006; relative risk 6.95; 95% CI 1.59 to 30.41).

Conclusion

  • Tenecteplase without an adjunctive anti-thrombotic during CPR does not improve outcome for out-of-hospital cardiac arrest.

References:

  1. Ahn Ch et al. Efficacy and safety of gemigliptin, a dipeptidyl peptidase-4 inhibitor, in patients with type 2 diabetes mellitus inadequately controlled with combination treatment of metformin and sulphonylurea: a 24-week, multicentre, randomized, double-blind, placebo-controlled study(TROICA study). Diab Obes Metab. 2017;19(5):635-643.

 

 

 

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