Acute Pulmonary Embolism, intermediate high risk (visible impact on right ventricular structure and function, and biochemical markers og myocardial damage according to the European Society of Cardiology Guidelines) MedDRA version: 21.0 Level: PT Classification code 10037377 Term: Pulmonary embolism System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Trade Name: Actilyse
Product Name: Actilyse
Pharmaceutical Form: Powder and solvent for concentrate for solution for infusion
INN or Proposed INN: Alteplase
CAS Number: 105857-23-6
Other descriptive n
Sponsors
Copenhagen University Hospital Rigshospitalet
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Age = 18 years 2) Informed consent for trial participation 3) Intermediate high-risk PE according to ESC criteria 4) Thrombus visible in main, lobar or segmental pulmonary arteries on CT angiography 5) 14 days of symptoms or less 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 140 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 70
Exclusion criteria
Exclusion criteria: 1) Altered mental state (GCS 24 hour since CT angiography) 3) Females of child bearing potential, unless negative HCG test is present 4) Thrombolysis for PE within 14 days of randomization 5) Thrombus passing through patent Foramen Ovale (risk of paradoxical embolism) 6) Ongoing oral anticoagulation therapy (heparins, aspirin, antiplatelet therapy and NOAC allowed) 7) Comorbidity making 6 months survival unlikely 8) Absolute contraindications for thrombolysis a. Hemorrhagic stroke or stroke of unknown origin at any time b. Ischemic stroke in the preceding 6 months c. Central nervous system damage or neoplasms d. Recent major trauma/surgery/head injury in the preceding 3 weeks e. Gastrointestinal bleeding within the last month f. Known bleeding risk Relative contraindications do not preclude randomization. Relative contraindications include: Transient ischemic attack in the preceding 6 months, Oral anticoagulant therapy, Pregnancy, or within one week pPost partum, Non-compressible puncture site, Traumatic resuscitation, Refractory hypertension (systolic blood pressure >180 mm Hg), Advanced liver disease, Infective endocarditis, Active peptic ulcer
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the efficacy of low dose thrombolytics administered intravenously or via pulmonary artery catheter to usual care (including heparins) on segemental pulmonary perfusion using the MIller Score;Secondary Objective: Secondary outcomes: 1) Reduction in Miller Score comparing low dose rtPA by intravenous route and via USAT. 21) Reduction in D-dimer from baseline to 48-96h post intervention. 32) Incidence of TR gradient > 40 mmHg at 3 months follow-up echocardiography. 34) Relative reduction in TnI/T from baseline to 48-96 h post intervention. 45) Bleeding complications (major and minor bleeding complication according the TIMI classification). 56) Mortality in the three groups (log-rank) and hazard ratio in multivariable analysis using the UFH/LMWH as reference. 67) NT-pro-BNP at 3 months follow-up, 78) 6 minute walk distance at 3 months follow-up 89) Quality of life at 3 months follow-up comparing the three groups (SF-36 and 5Q-DL);Primary end point(s): CO-PRIMARY ENDPOINT •Reduction in modified Miller score (score of thrombus involvement and segmental flow)(13, 14)(13;14) comparing thrombolysis groups (combining groups with and without USAT) to heparin/LMWH groupgroup, p<0.01 (n=140 vs. n=70). •Reduction in modified Miller score (score of thrombus involvement and segmental flow)(13, 14) comparing thrombolysis administered by USAT or IV, p<0.04 (n=70 vs n=70) ;Timepoint(s) of evaluation of this end point: Primary endpoints are evaluated within 96 hours from randomization | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Reduction in modified Miller score (score of thrombus involvement and segmental flow)(13;14) comparing the group treated with thrombolysis without USAT to thrombolysis with USAT • Reduction in D-dimer from baseline to 48-96h post randomization • Incidence of TR gradient > 40 mmHg at 3 months follow-up echocardiography • Relative reduction in TnI/T from baseline to 48-96 h post intervention • Bleeding complications (major and minor bleeding complication according the TIMI classification) • Dyspnea index (Visual analog scale) after 48-96 h and after 3 months • Mortality in the three groups (log-rank), and hazard ratio in multivariable analysis using the UFH/LMWH as reference • Reduction in NT-pro-BNP at 48-96 hours and 3 months • 6MWD at 3 months comparing the three groups • Quality of life at 3 months follow-up comparing the three groups (SF-36 and 5Q-DL);Timepoint(s) of evaluation of this end point: Secondary endpoints are evaluated within 3 months from randomization | — |
Countries
Denmark
Contacts
Public ContactDepartment of Cardiology
Copenhagen University Hospital Rigshospitalet
Outcome results
None listed