Safety and Efficacy of Heparin for 72 Hours Followed by Dabigatran for the Treatment of Acute Pulmonary Embolism.

Phase 1

• Conditions: Acute Intermediate-Risk Pulmonary Embolism; MedDRA version: 20.0Level: HLTClassification code 10037379Term: Pulmonary embolism and thrombosisSystem Organ Class: 100000004866; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2015-001830-12-IT
• Lead Sponsor: IVERSITY MEDICAL SCHOOL OF THE JOHANNES GUTENBERG UNIVERSITY MAINZ

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-02-16
• Last Update Posted: 5 April 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 530

Inclusion Criteria

1) Age =18 years;
2) Objectively confirmed diagnosis of acute PE by multidetector CT angiography, ventilation/perfusion lung scan, or selective invasive pulmonary angiography, according to established diagnostic criteria;
3) Absence of hemodynamic collapse/decompensation at presentation;
4) Intermediate-risk category of PE severity indicated by the presence of at least one of the following a, b, or c criteria:a) At least one sign of RV pressure overload/dysfunction on CT angiography or echocardiography:
a1) on CT angiography, RV pressure overload/dysfunction is defined as RV/LV end-diastolic diameter ratio >1.0; or
a2) on echocardiography, RV pressure overload/dysfunction is defined by the presence of at least one of the following findings:
• RV/LV end-diastolic diameter ratio >1.0 (apical or subcostal 4-chamber view);
• RV end-diastolic diameter >30 mm (parasternal long-axis or short-axis view);
• RV free wall hypokinesis (any view);
• Tricuspid regurgitant jet velocity >2.6 m/s from the apical or subcostal 4-chamber view, or the parasternal short-axis view;
• Absence of inspiratory collapse of the inferior vena cava.
b) Signs of myocardial injury as indicated by elevated troponin levels:
• Troponin elevation is defined as an abnormal result of any validated troponin test based on the reference values determined by the local Department of Clinical Chemistry at each participating site;
c) Signs of (RV) failure as indicated by NT-proBNP levels >600 pg/ml
5) Signed and dated informed consent of the subject available.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 500
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 200

Exclusion Criteria

1) Pregnancy or women of childbearing potential who do not practice a medically accepted highly effective contraception during the trial and one month beyond;
2) 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;
3) Need for long-term treatment with a low molecular weight heparin, a vitamin K antagonists, or a new oral anticoagulant (rivaroxaban, dabigatran, apixaban or edoxaban), for an indication other than the index PE episode; or for antiplatelet agents except a etylsalicylic acid at a dosage =100 mg/day;
4) Active bleeding or known significant bleeding risk;
5) Renal insufficiency with estimated creatinine clearance <30 ml/min/1.73m2;
6) Non-compliance or inability to adhere to treatment or to the follow-up visits;
7) Life expectancy less than 6 months.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective is to determine whether treatment of acute intermediate-risk PE (as defined by the inclusion and exclusion criteria) with parenteral anticoagulation for at least 72 hours after diagnosis, followed by dabigatran over 6 months, is effective and safe.;Secondary Objective: The secondary objective is to assess the recovery of right ventricular function over the first 6¿1 days of treatment, or upon discharge, and to evaluate its importance for the 6-months prognosis of patients with intermediate-risk PE.;Primary end point(s): The primary outcome is whether symptomatic VTE or EP-related death occurs within the first 6 months of anticoagulant therapy (yes/no(. Symptomatic VTE or EP-related death are defined in chapter 2.2 of the Protocol;Timepoint(s) of evaluation of this end point: 6 months after anticoagulation therapy

Secondary Outcome Measures

Name	Time	Method
Timepoint(s) of evaluation of this end point: 30 days, 6 months after PE diagnosis;Secondary end point(s): 1) Recovery or RV function at 6¿1 days after PE diagnosis or upon discharge (wichever comes first) and at 6-month follow-up, as assessed by echocardiography;<br>2) Course of NT-proBNP levels during follow-up (measurement at baseline, 6¿1 days or at discharge, and 6-month follow-up);<br>3) Death from any cause, or hemodynamic collapse or decompensation, within the first 30 days;<br>4) PE-related death, or PE-related hemodynamic collapse or decompensation, within the forst 30 days;<br>5) Overall duration of hospital stay (index event and repeated hospitalizations due to PE [index or recurrent event] or to a bleeding event) within 6 months;<br>6) Death from any cause within 6 months.