E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
acute intermediate-risk of pulmonary embolism |
acute intermediate-risk of pulmonary embolism |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10014521 |
E.1.2 | Term | Embolism pulmonary |
E.1.2 | System Organ Class | 100000015973 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary outcome is whether symptomatic Venous thromboembolism or Pulmonary Embolism-related death occurs within the first 6 months of anticoagulation therapy (yes/no). Symptomatic VTE and PE-related death |
The primary outcome is whether symptomatic Venous thromboembolism or Pulmonary Embolism-related death occurs within the first 6 months of anticoagulation therapy (yes/no). Symptomatic VTE and PE-related death |
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E.2.2 | Secondary objectives of the trial |
1) Recovery of RV function at 6±1 days after PE diagnosis or upon discharge (whichever comes first) and at 6-month follow-up, as assessed by echocardiography; 2) Course of NT-proBNP levels during follow-up (measurement at baseline, 6±1 days or at discharge, and 6-month follow-up); 3) Death from any cause, or hemodynamic collapse or decompensation, within the first 30 days; 4) PE-related death, or PE-related hemodynamic collapse or decompensation, within the first 30 days; 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; 6) Death from any cause within 6 months.
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1) Recovery of RV function at 6±1 days after PE diagnosis or upon discharge (whichever comes first) and at 6-month follow-up, as assessed by echocardiography; 2) Course of NT-proBNP levels during follow-up (measurement at baseline, 6±1 days or at discharge, and 6-month follow-up); 3) Death from any cause, or hemodynamic collapse or decompensation, within the first 30 days; 4) PE-related death, or PE-related hemodynamic collapse or decompensation, within the first 30 days; 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; 6) Death from any cause within 6 months.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 (8,23): 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.
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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 (8,23): 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.
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E.4 | Principal 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 VTE; or for antiplatelet agents except acetylsalicylic 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. |
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 VTE; or for antiplatelet agents except acetylsalicylic 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome is whether symptomatic Venous thromboembolism or Pulmonary Embolism--related death occurs within the first 6 months of anticoagulation therapy (yes/no). |
The primary outcome is whether symptomatic Venous thromboembolism or Pulmonary Embolism--related death occurs within the first 6 months of anticoagulation therapy (yes/no). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1) Recovery of RV function at 6±1 days or upon discharge (whichever comes first) and at 6-month follow-up, as assessed by echocardiography; RV recovery 2) Temporal pattern of changes in NT-proBNP levels during follow-up (measurement at baseline, 6±1 days or at discharge, and at 6 months) 3) Death from any cause, or hemodynamic collapse or decompensation, within the first 30 days; |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |