Pradaxa or Warfarin for Prevention of Recurrent VTE in Patients With Angiographically Confirmed Acute Massive Pulmonary Embolism undergoIng Endovascular Mechanical Fragmentation and Thrombolytic Therapy

Study Overview
=================
Brief Summary
-----------------
A prospective randomised controlled study to evaluate outcomes of the treatment with pradaxa or warfarin for prevention of recurrent DVT in patients with angiographically confirmed acute massive pulmonary embolism undergoIng endovascular mechanical fragmentation and thrombolytic therapy. [RE-SPIRE study]

Official Title
-----------------
A Prospective Randomised Controlled Study to Evaluate Outcomes of the Treatment With Pradaxa or Warfarin for Prevention of Recurrent VTE in Patients With Angiographically Confirmed Acute Massive Pulmonary Embolism Undergoing Endovascular Mechanical Fragmentation and Thrombolytic Therapy

Conditions
-----------------
Angiographically Confirmed Acute Massive Pulmonary Embolism Treated With Endovascular Mechanical Fragmentation and Thrombolytic Therapy

Intervention / Treatment
-----------------
* Drug: Dabigatran Etexilate
* Drug: Warfarin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men and women aged > 18 years Angiographically confirmed acute massive pulmonary embolism with involvement of Central pulmonary arteries. endovascular mechanical thrombus fragmentation + thrombolytic therapy (using recombinant tissue activator of plasminogen), performed for treatment of the above-mentioned pulmonary embolism in less than 48 hours before randomization. The patient should be randomized no earlier than 24 hours after procedures endovascular mechanical thrombus fragmentation + thrombolytic therapy Written informed consent signed by patient. Exclusion Criteria: Signs of hemodynamic instability (i.e. systolic blood pressure <100 mm Hg.St. or episode of systolic blood pressure fall for ≥40 mm Hg. / or heart rate > 110 lasting more than 15 min) or need for ventilatory support within 12 hours prior to randomisation. The indication for oral anticoagulation, associated with others disease. malignant neoplasm of any location Contraindications to warfarin or pradaxa according to Russian Instructions for medical use of these drugs Indications for concomitant treatment with antiplatelet agents Any stroke within 6 months before randomization Intracranial hemorrhage in anamnesis Active bleeding, bleeding diathesis. Clinically significant bleeding within the last 30 days. Trauma or extensive surgery within 1 month before randomization or surgery planned in the next 6 months after randomization. Intracranial pathology: tumor, arteriovenous fistula or aneurysm. Gastrointestinal bleeding in the previous 3 months. Gastric ulcer or duodenal ulcer with clinical manifestations or endoscopically identified acute ulcer without signs of scarring during previous 30 days. Uncontrolled hypertension (systolic blood pressure> 180 mm Hg. and / or diastolic blood pressure> 100 mm.hg in patients receiving antihypertensive drugs). Pregnancy, lactation. Life expectancy <6 months. Clinically significant liver disease. Creatinine clearance (estimated by Cockcroft-Gault) <30 ml / min. hemoglobin level <90 g/l), thrombocytopenia <100x10^9 / L. Patients who, in the opinion of the researcher, are not suitable for inclusion in the study, for example, due to the low likelihood of doctor's recommendations following. Long-term use of NSAIDs Current participation in another clinical study. Allergic to contrast substance or radioisotope drugs used in procedures to assess endpoints of the study, which according to researchers, may be a contraindication to the implementation of these research methods.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: group of dabigatran<br> | Drug: Dabigatran Etexilate<br>* All patients in this group continue to receive unfractionated heparin for 5-7 days, and then transferred to the drug Pradaxa dose of 150 mg 2 times a day. Pradaxa administration continued until the end of the treatment period. The treatment period starts on the day of randomization and lasts for 6 months.<br>|
| Active Comparator: group of warfarin<br> | Drug: Warfarin<br>* all patients continue to receive unfractionated heparin intravenously and at the same time (from the date of randomization) start warfarin, accompanied by regular measurement of the INR every day or every other day. As soon as INR reaches the range of 2.0 to 3.0, the administration of the unfractionated heparin should be discontinued. Further measurements of INR should be performed once a month during outpatient visits. The patient continues to receive warfarin under the control of the INR till the end of the treatment period. The treatment period starts on the day of randomization and lasts for 6 months.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| recurrent PE | according to Echocardiogram, scintigraphy of the lungs | 6 month | 
| death |  | 6 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| hemorrhagic complications | according to the ISTH criteria | 6 month | 
| postembolic residual pulmonary hypertension | according to scintigraphy of the lungs | 6 month | 
| recurrent deep vein thrombosis | according to ultrasound of the deep veins | 3 month | 
| recurrent deep vein thrombosis | according to ultrasound of the deep veins | 6 month | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Dabigatran etexilate, Recurrence of DVT, Pulmonary Embolism, Warfarin