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

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

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]

Study Overview

• Status: Unknown
• Conditions: Angiographically Confirmed Acute Massive Pulmonary Embolism Treated With Endovascular Mechanical Fragmentation and Thrombolytic Therapy
• Intervention / Treatment: Drug: Dabigatran Etexilate; Drug: Warfarin

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 4

Contacts and Locations

Study Locations

• Russian Federation
  • Novosibirsk, Russian Federation, 630055
    • Recruiting
    • Federal State Institution Academician E.N.Meshalkin Novosibirsk State Research Institute Of Circulation Pathology Rusmedtechnology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: group of dabigatran	Drug: Dabigatran Etexilate; 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.
Active Comparator: group of warfarin	Drug: Warfarin; 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.

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

Collaborators and Investigators

• Sponsor: Meshalkin Research Institute of Pathology of Circulation

Study record dates

Study Major Dates

• Study Start: October 1, 2016
• Primary Completion (Anticipated): June 1, 2018
• Study Completion (Anticipated): June 1, 2018

Study Registration Dates

• First Submitted: November 22, 2016
• First Submitted That Met QC Criteria: November 30, 2016
• First Posted (Estimate): December 1, 2016

Study Record Updates

• Last Update Posted (Estimate): December 20, 2016
• Last Update Submitted That Met QC Criteria: December 19, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Warfarin; Pulmonary Embolism; Dabigatran etexilate; Recurrence of DVT
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Embolism and Thrombosis; Embolism; Pulmonary Embolism; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Dabigatran; Warfarin
• Other Study ID Numbers: RE-SPIRE study

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO