Low Molecular Weight Heparin for 72 Hours Followed by Dabigatran for Acute Intermediate-Risk Pulmonary Embolism.

Study Overview
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Brief Summary
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This prospective, multicenter, multinational, phase IV, interventional single-armed (management) trial will focus on the safety, efficacy and cost-effectiveness of a new oral anticoagulant in the treatment of patients with acute intermediate-risk PE based on validated imaging (echocardiographic or CT angiographic) and laboratory biomarker (circulating levels of cardiac troponins and natriuretic peptides) parameters and their combinations.

Official Title
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Safety and Efficacy of Low Molecular Weight Heparin for 72 Hours Followed by Dabigatran for the Treatment of Acute Intermediate-Risk Pulmonary Embolism

Conditions
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Pulmonary Embolism

Intervention / Treatment
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* Drug: Dabigatran


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years Objectively confirmed diagnosis of acute PE by multidetector CT angiography, ventilation/perfusion lung scan, or selective invasive pulmonary angiography, according to established diagnostic criteria, with or without symptomatic deep vein thrombosis Absence of hemodynamic collapse, or decompensation, at presentation; Hemodynamic collapse or decompensation Intermediate-risk category of PE severity indicated by a positive (score ≥1) simplified pulmonary embolism severity index (sPESI), in combination with the presence of at least one of the following criteria at presentation: At least one sign of RV pressure overload/dysfunction on CT angiography or echocardiography Signs of myocardial injury as indicated by elevated troponin levels Signs of (RV) failure as indicated by NT-proBNP levels >600 pg/ml at baseline. Ability of the subject to understand the character and individual consequences of the clinical trial; signed and dated informed consent of the subject available before the start of any specific trial procedures Exclusion Criteria: Pregnancy (a negative serum or urine pregnancy test should be available for women of child-bearing potential before study inclusion) or lactation Women of childbearing potential who do not practice a medically accepted highly effective contraception during the trial and one month beyond History of hypersensitivity to the investigational medicinal product or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product Participation in another clinical trial during the present clinical trial or within the last three months Medical or psychological condition that would not permit completion of the trial or signing of informed consent Use of a fibrinolytic agent, surgical thrombectomy, interventional (catheter-directed) thrombus aspiration or lysis, or use of a cava filter to treat the index episode of PE Treatment with any therapeutically dosed anticoagulant for more than 48 hours prior to enrolment Need for long-term treatment with a low molecular weight heparin, vitamin K antagonists or NOAC, for an indication other than the index PE episode, or for antiplatelet agents except acetylsalicylic acid at a dosage ≤100 mg/day; Active bleeding or known significant bleeding risk (e.g., gastrointestinal ulcer, malignant neoplasms, injuries or recent surgeries of the brain, spinal cord or eyes, recent intracranial bleedings, known or suspected esophagus varices, aneurysms or intraspinal or intracranial vascular abnormalities) Artificial heart valves requiring treatment with an anticoagulant Renal insufficiency with estimated creatinine clearance <30 ml/min/1.73m2 Chronic liver disease with aminotransferase levels two times or more above the local upper limit of normal range Concomitant administration of strong inhibitors of P-glycoprotein like ketoconazole, cyclosporin, itraconazole or dronedarone Unwillingness or inability to adhere to treatment or to the follow-up visits Life expectancy less than 6 months

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dabigatran treatment<br>Low molecular weight heparin for 72 hours followed by 6 months of dabigatran | Drug: Dabigatran<br>* Low molecular weight heparin for 72 hours followed by 6 months of dabigatran<br>* Other names: Pradaxa;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of symptomatic venous thromboembolism (VTE) or pulmonary embolism (PE) related death (yes/no) |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recovery of right ventricle (RV) function |  | 6±1 days or upon discharge (whichever comes first), 6 months | 
| Temporal pattern of changes in NT-proBNP (N-terminal prohormone of brain natriuretic peptide) levels |  | 6±1 days or upon discharge (whichever comes first), 6 months | 
| Death from any cause |  | 30 days | 
| Pulmonary embolism (PE) related death, or PE-related or hemodynamic collapse or decompensation |  | 30 days | 
| Overall duration of hospital stay |  | 6 months | 
| Major bleeding |  | 6 months | 
| Clinically relevant bleeding |  | 6 months | 
| Serious adverse events (SAE) |  | 72 hours, 30 days, 6 months |