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

Rigshospitalet

Status and phase: Active, not recruiting; Phase 3

Conditions: Pulmonary Embolism

Treatments: Drug: Alteplase 20 Mg Powder for Solution for Injection Vial; Device: Ultrasound assisted Thrombolysis

Study type: Interventional

Funder types: Other

Identifiers

NCT04088292

STRATIFY-1

Details and patient eligibility

About

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

Full 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

Enrollment: 210 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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210 participants in 3 patient groups

USAT + low dose thrombolysis

Active Comparator group

Description:

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

Treatment:

Device: Ultrasound assisted Thrombolysis

Drug: Alteplase 20 Mg Powder for Solution for Injection Vial

Low dose thrombolysis

Active Comparator group

Description:

Intravenous low dose thrombolysis (20 mg of rtPA, Alteplase) over 6 hours plus UFH or low molecular weight heparin (LMWH).

Treatment:

Drug: Alteplase 20 Mg Powder for Solution for Injection Vial

Heparin alone

No Intervention group

Description:

UFH or low molecular weight heparin (LMWH) only (with option for conventional thrombolysis according to local protocols for hemodynamic deterioration)