PEITHO Pulmonary Embolism Thrombolysis Study

• Clinical composite endpoint of all-cause mortality or haemodynamic collapse within 7 days [ Time Frame: Day 7 ] [ Designated as safety issue: Yes ]
  
• Haemodynamic collapse is defined as: need for cardiopulmonary resuscitation; or systolic blood pressure < 90 mm Hg for at least 15 min or drop of syst [ Time Frame: Day 7 ] [ Designated as safety issue: Yes ]
  

• Death within 7 days [ Time Frame: Day 7 ] [ Designated as safety issue: Yes ]
  
• Haemodynamic collapse within 7 days [ Time Frame: Day 7 ] [ Designated as safety issue: Yes ]
  
• Confirmed symptomatic pulmonary embolism recurrence within 7 days [ Time Frame: Day 7 ] [ Designated as safety issue: Yes ]
  
• Death within 30 days [ Time Frame: Day 30 ] [ Designated as safety issue: Yes ]
  
• Total strokes (intra cranial haemorrhage or ischaemic stroke) within 7 days [ Time Frame: Day 7 ] [ Designated as safety issue: Yes ]
  
• Major bleeding (other intracranial haemorrhage or ischaemic stroke) [ Time Frame: Day 7 ] [ Designated as safety issue: Yes ]
  

A prospective, randomized, double-blind, placebo-controlled, international, multicentre, parallel-group comparison trial evaluating the efficacy and safety of single i.v. bolus tenecteplase plus standard anticoagulation as compared with standard anticoagulation in normotensive patients with acute pulmonary embolism and with echocardiographic and laboratory evidence of right ventricular dysfunction.Patients suffering from acute pulmonary embolism (first symptoms occurring within 15 days) confirmed by lung scanning or a positive spiral computed tomogram, or a positive pulmonary angiogram, presenting with right ventricular dysfunction on echocardiography and tested troponin I or T positive will be included in the study if they have no exclusion criteria.Patients in the investigational group will receive: Ø Tenecteplase as a single body-weight (known or estimated) adjusted IV bolus administered over 5 - 10 seconds not later than 30 minutes after randomization, and not later than 2 hours after the diagnosis of RV dysfunction Weight (kg) Dose in mg Dose in units Dose in ml<60 30 mg 6000 U 6 ml>60 to <70 35 mg 7000 U 7 ml>70 to <80 40 mg 8000 U 8 ml>80 to <90 45 mg 9000 U 9 ml>90 50 mg 10000 U 10 mlØ and: concomitant therapy-Unfractionated heparin at a dose of 80 IUxKg-1 as an intravenous bolus, followed by an infusion of 18 IUxKg-1xh-1, to be administered immediately after randomization in all patients for at least 48 hours following randomization. Beyond this period, intravenous UFH may be substituted with subcutaneous heparin (LMWH) treatment. The bolus will be omitted when heparin was started before randomisation.Patients in the control group will receive Ø placebo as a single body-weight (known or estimated) adjusted IV bolus administered over 5 - 10 seconds not later than 30 minutes after randomization, and not later than 2 hours after the diagnosis of RV dysfunction. Weight (kg) Dose in ml<60 6 ml>60 to <70 7 ml>70 to <80 8 ml>80 to <90 9 ml>90 10 mlØ and concomitant therapy with Unfractionated heparin