E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Isolated subsegmental pulmonary embolism |
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E.1.1.1 | Medical condition in easily understood language |
Small blood clots in the pulmonary arteries, so called isloated pulmonary embolism. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
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 overall objective of this trial will be to evaluate the efficacy and safety of clinical surveillance without anticoagulation in low-risk patients with isolated SSPE. Objective 1: To compare the frequency of symptomatic, recurrent venous thromboembolism (VTE) in low-risk patients with isolated SSPE randomized to receive clinical surveillance or anticoagulation. |
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E.2.2 | Secondary objectives of the trial |
Objective 2: To compare the frequency of clinically significant bleeding and all-cause mortality in low-risk patients with isolated SSPE randomized to receive clinical surveillance or anticoagulation. Objective 3: To compare health-related quality of life, functional status, and medical resource utilization in low-risk patients with isolated SSPE randomized to receive clinical surveillance or anticoagulation.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Informed Consent as documented by signature 2) Age ≥18 years 3) Objective diagnosis of symptomatic or asymptomatic isolated SSPE
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E.4 | Principal exclusion criteria |
1) Presence of leg deep vein thrombosis (DVT) or upper extremity DVT (subclavian vein or above) 2) Active cancer, defined as cancer treated with surgery, chemotherapy, radiotherapy, or palliative care during the last 6 months 3) ≥1 prior episode of unprovoked VTE (absence of a transient or permanent risk factor) 4) Clinical instability (systolic blood pressure <100 mm Hg or arterial oxygen saturation <92% at ambient air) at the time of presentation 5) Active bleeding or at high risk of bleeding 6) Severe renal failure (creatinine clearance <30ml/min) 7) Severe liver insufficiency (Child-Pugh B or C) 8) Concomitant use of strong CYP3A4 inhibitors or strong CYP3A4 inducers 9) Known hypersensitivity to rivaroxaban 10) Need for therapeutic anticoagulation for another reason 11) Therapeutic anticoagulation for >72 hours for any reason at the time of screening 12) Hospitalized for >72 hours prior to the diagnosis of isolated SSPE (hospital-acquired VTE) 13) Known pregnancy or breast feeding (pregnancy test to be performed for women of childbearing potential) 14) Lack of safe contraception in women of childbearing potential 15) Refusal or inability to provide informed consent 16) Prior enrolment in this trial
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome will be the proportion of recurrent, clinically symptomatic, objectively confirmed VTE within 90 days of randomization, defined as recurrent fatal or nonfatal pulmonary embolism (PE) or lower limb deep vein thrombosis (DVT; efficacy).
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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) |
The secondary outcomes will be the proportion of clinically significant bleeding and all-cause mortality at 90 days of randomization (safety). The ancillary outcomes will be health-related quality of life, functional status, and medical resource utilization at 90 days of randomization. In a post-hoc analysis, we will also assess radiological inter-observer agreement for SSPE. |
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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 | Yes |
E.6.5 | Efficacy | Yes |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Anticoagulation with Rivaroxaban |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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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Last visit of the last subject |
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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 | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |