Low Dose Thrombolysis, Ultrasound Assisted Thrombolysis or Heparin for Intermediate High Risk Pulmonary Embolism

Pulmonary Embolism Clinical Trial

— STRATIFY  

Official title:

Low Dose Thrombolysis, Ultrasound Assisted Thrombolysis or Heparin for Intermediate High Risk Pulmonary Embolism

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04088292
• Other study ID #: STRATIFY-1
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 6, 2019
• Est. completion date: October 31, 2024

Study information

• Verified date: June 2024
• Source: Rigshospitalet, Denmark
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Open label clinical randomized trial comparing three strategies for managing acute intermediate-high risk pulmonary embolism

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 210
• Est. completion date: October 31, 2024
• Est. primary completion date: June 5, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Embolism
• Pulmonary Embolism

Intervention

Drug:
• Alteplase 20 Mg Powder for Solution for Injection Vial
Low dose alteplase delivered IV or bu Ultrasound Assisted Thrombolysis device

Device:
• Ultrasound assisted Thrombolysis
Ultrasound assisted thrombolysis (USAT)

Locations

Country	Name	City	State
Denmark	Copenhagen University Hospital Bispebjerg Hospital	Bispebjerg
Denmark	Copenhagen University Hospital Rigshospitalet	Copenhagen
Denmark	Copenhagen University Hospital Gentofte	Gentofte	Capital Region
Denmark	Copenhagen University Hospital, Herlev Gentofte Hospital	Herlev

Sponsors (5)

Lead Sponsor	Collaborator
Rigshospitalet, Denmark	Copenhagen University Hospital, Hvidovre, Herlev and Gentofte Hospital, Hillerod Hospital, Denmark, University Hospital Bispebjerg and Frederiksberg

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Reduction in Miller score comparing low dose thrombolysis and heparin alone groups	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)	at 48 to 96 hours post randomization
Primary	Reduction i Miller score comparing low dose thrombolysis by iv and by USATgroups	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)	at 48 to 96 hours post randomization
Secondary	Incidence of bleeding complications	Bleeding complications (major and minor bleeding complication according the TIMI classification)	Until hospital discharge, on average 1 week
Secondary	Length of stay of index admission	Duration of index admission, including hospital based rehabilitation	End of study, expected to be 5 years
Secondary	Dyspnea index by visual analogue scale	Dyspnea index (Visual analog scale) after 48-96 h and after 3 months	End of study, expected to be 5 years
Secondary	Change in oxygen supplement (FiO2)	FiO2 (in %)	at 48 to 96 hours post randomization
Secondary	Mortality rate	Mortality in the three groups (log-rank), and hazard ratio in multivariable analysis using the UFH/LMWH as reference	End of study, expected to be 5 years
Secondary	Incidence of Pulmonary Hypertension	Incidence of TR gradient > 40 mmHg at 3 months follow-up echocardiography	3 months follow-up
Secondary	6 minute walk distance af follow-up	6 minute walk distance at 3 months follow-up visit	3 months follow-up
Secondary	Health related Quality of Life (PEmb-QoL)	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	3 months follow-up
Secondary	Health related Quality of Life (EQ-5D-5L)	5Q-5D-5L (EuroQoL 5 dimension, 5 level questionnaire, ranging from -0.59 to 1, where 1 is the best possible health state)	3 months follow-up