Pulmonary Embolism
Conditions
Brief summary
Open label clinical randomized trial comparing three strategies for managing acute intermediate-high risk pulmonary embolism
Detailed description
Trial acronym: STRATIFY Background: Intermediate-high risk pulmonary embolism (PE) is associated with a significant risk of death or hemodynamic deterioration. The optimal treatment strategy should balance efficacy in reducing thrombus burden and hemodynamic compromise with risk of complications, in particular bleeding. Previous studies have investigated conventional high-dose, short term thrombolysis by (rtPA), finding a reduction in risk hemodynamic deterioration, but no reduction in mortality and a substantial increase in significant bleeding complications. Catheter based techniques and low dose thrombolysis may offer lower risk of complication with reasonable efficacy. Such studies have not been performed in RCTs with a reasonable sample size, and no study have compared low dose intravenous thrombolysis and catheter based techniques. The current trial addresses this paucity of data by randomizing patients to one of three treatment modalities: Intervention: 1:1:1 randomization, stratified for site to * UltraSound Assisted Thrombolysis (USAT) with low dose thrombolysis (20 mg of rtPA, Alteplase) over 6 hours plus unfractionated heparin (UFH) or low molecular weight heparin (LMWH) within 12 hours of randomization * Intravenous low dose thrombolysis (20 mg of rtPA, Alteplase) over 6 hours plus UFH or low molecular weight heparin (LMWH). * UFH or low molecular weight heparin (LMWH) only (with option for conventional thrombolysis according to local protocols for hemodynamic deterioration) Design: Regional collaborative, randomized trial with 1:1:1 allocation of 210 patients with acute intermediate-high risk PE with no absolute contraindications to thrombolysis
Interventions
DRUGAlteplase 20 Mg Powder for Solution for Injection Vial
Low dose alteplase delivered IV or bu Ultrasound Assisted Thrombolysis device
Ultrasound assisted thrombolysis (USAT)
Sponsors
Herlev and Gentofte Hospital
University Hospital Bispebjerg and Frederiksberg
Hillerod Hospital, Denmark
Copenhagen University Hospital, Hvidovre
Rigshospitalet, Denmark
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Primary endpoint will be assessed by assessor blinded to the intervention
Intervention model description
Randomized clinical trial with 1:1:1 allocation to treatment strata
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Exclusion criteria
1. Altered mental state (GCS \< 14) 2. No qualifying CT angiography performed (\> 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 1. Hemorrhagic stroke or stroke of unknown origin at any time 2. Ischemic stroke in the preceding 6 months 3. Central nervous system damage or neoplasms 4. Recent major trauma/surgery/head injury in the preceding 3 weeks 5. Gastrointestinal bleeding within the last month 6. Known bleeding risk
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reduction in Miller score comparing low dose thrombolysis and heparin alone groups | at 48 to 96 hours post randomization | Reduction in Miller Score and on follow-up (48-96 h) CT pulmonary Angiography comparing low-dose rtPA (±USAT) to UFH/LMWH group (p\<0.01, N=210) |
| Reduction i Miller score comparing low dose thrombolysis by iv and by USATgroups | at 48 to 96 hours post randomization | reduction in Miller Score and on follow-up (48-96 h) CT pulmonary Angiography comparing low-dose rtPA by USAT to iv, p\<0.04, N=140) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dyspnea index by visual analogue scale | End of study, expected to be 5 years | Dyspnea index (Visual analog scale) after 48-96 h and after 3 months |
| Change in oxygen supplement (FiO2) | at 48 to 96 hours post randomization | FiO2 (in %) |
| Mortality rate | End of study, expected to be 5 years | Mortality in the three groups (log-rank), and hazard ratio in multivariable analysis using the UFH/LMWH as reference |
| Incidence of bleeding complications | Until hospital discharge, on average 1 week | Bleeding complications (major and minor bleeding complication according the TIMI classification) |
| 6 minute walk distance af follow-up | 3 months follow-up | 6 minute walk distance at 3 months follow-up visit |
| Health related Quality of Life (PEmb-QoL) | 3 months follow-up | Health related Quality of Life at 3 months follow-up using PEmb-QoL (Pulmonary Embolism Quality of Life) ranging from 0 to 100, higher score indicating worse Quality of Life |
| Health related Quality of Life (EQ-5D-5L) | 3 months follow-up | 5Q-5D-5L (EuroQoL 5 dimension, 5 level questionnaire, ranging from -0.59 to 1, where 1 is the best possible health state) |
| Incidence of Pulmonary Hypertension | 3 months follow-up | Incidence of TR gradient \> 40 mmHg at 3 months follow-up echocardiography |
| Length of stay of index admission | End of study, expected to be 5 years | Duration of index admission, including hospital based rehabilitation |
Countries
Denmark
Outcome results
None listed