PEITHO Pulmonary Embolism Thrombolysis Study

Study Overview
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Brief Summary
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Heparin is the reference therapy for most patients with pulmonary embolism. Some patients with sub-massive pulmonary embolism defined by normal blood pressure and dysfunction of the right ventricle have a higher mortality risk. It has been suggested that thrombolytic treatment, a drug that dissolves blood clots more rapidly, may reduce the mortality in those patients. The studies reported to date were unable to confirm or refute this hypothesis because the number of patients included in those studies is too low. The aim of the study is to compare thrombolytic treatment with heparin (which is the reference therapy for pulmonary embolism) in a large group of patients with sub-massive pulmonary embolism.

Detailed Description
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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

Official Title
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Comparison Trial Evaluating Efficacy and Safety of Single i.v. Bolus Tenecteplase Plus Standard Anticoagulation as Compared With Standard Anticoagulation in Normotensive Patients

Conditions
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Pulmonary Embolism

Intervention / Treatment
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* Drug: placebo ( group B)
* Drug: tenecteplase (group A)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or older Acute PE (first symptoms occurring 15 days or less before randomisation) confirmed by lung scan, or a positive spiral computed tomogram, or a positive pulmonary angiogram Right ventricular dysfunction confirmed by echocardiography or spiral computed tomography of the chest and a positive troponin I or T test Exclusion criteria: Haemodynamic collapse at presentation as defined above Known significant bleeding risk Administration of thrombolytic agents within the previous 4 days Vena cava filter insertion or pulmonary thrombectomy within the previous 4 days Uncontrolled hypertension defined as systolic BP >180 mm Hg and/or diastolic BP >110 mm Hg at randomisation Treatment with an investigational drug under another study protocol in the previous 7 days or greater, according to local requirements Previous enrolment in this study Known hypersensitivity to tenecteplase, alteplase, unfractionated heparin, or to any of the excipients Pregnancy, lactation or parturition within the previous 30 days. Women of childbearing age must have a negative pregnancy test or use a medically accepted method of birth control Known coagulation disorder (including vitamin K antagonists) Any other condition that the investigator feels would place the patient at increased risk if the investigational therapy is initiated

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: group A<br>tenecteplase (group A) | Drug: tenecteplase (group A)<br>* tenecteplase (group A)<br>|
| Placebo Comparator: group B<br>placebo ( group B) | Drug: placebo ( group B)<br>* placebo ( group B)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical composite endpoint of all-cause mortality or haemodynamic collapse within 7 days |  | Day 7 | 
| 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 |  | Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death within 7 days |  | Day 7 | 
| Haemodynamic collapse within 7 days |  | Day 7 | 
| Confirmed symptomatic pulmonary embolism recurrence within 7 days |  | Day 7 | 
| Death within 30 days |  | Day 30 | 
| Total strokes (intra cranial haemorrhage or ischaemic stroke) within 7 days |  | Day 7 | 
| Major bleeding (other intracranial haemorrhage or ischaemic stroke) |  | Day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pulmonary embolism, Heparin, Thrombolytic therapy, Bleeding