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

NCT04088292 | Active Not Recruiting Phase 3 DMC FDA Drug FDA Device

• 1 other identifier: STRATIFY-1
• Study Type: interventional
• Target: 210
• Locations: 1 country
• Sites: 4

Brief Summary

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

Conditions

Pulmonary Embolism

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (9)

• Incidence of bleeding complications

  Until hospital discharge, on average 1 week

• Length of stay of index admission

  End of study, expected to be 5 years

• Dyspnea index by visual analogue scale

  End of study, expected to be 5 years

• Change in oxygen supplement (FiO2)

  at 48 to 96 hours post randomization

• Mortality rate

  End of study, expected to be 5 years

Study Arms (3)

USAT + low dose thrombolysis

ACTIVE COMPARATOR

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

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

Low dose thrombolysis

ACTIVE COMPARATOR

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

Drug: Alteplase 20 Mg Powder for Solution for Injection Vial

Heparin alone

NO INTERVENTION

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

Interventions

Alteplase 20 Mg Powder for Solution for Injection Vial DRUG

Low dose alteplase delivered IV or bu Ultrasound Assisted Thrombolysis device

Low dose thrombolysis; USAT + low dose thrombolysis

Ultrasound assisted Thrombolysis DEVICE

Ultrasound assisted thrombolysis (USAT)

USAT + low dose thrombolysis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Informed consent for trial participation
• Intermediate high-risk PE according to ESC criteria
• Thrombus visible in main, lobar or segmental pulmonary arteries on CT angiography
• days of symptoms or less

You may not qualify if:

• Altered mental state (GCS \< 14)
• No qualifying CT angiography performed (\> 24 hour since CT angiography)
• Females of child bearing potential, unless negative HCG test is present
• Thrombolysis for PE within 14 days of randomization
• Thrombus passing through patent Foramen Ovale (risk of paradoxical embolism)
• Ongoing oral anticoagulation therapy (heparins, aspirin, antiplatelet therapy and NOAC allowed)
• Comorbidity making 6 months survival unlikely
• Absolute contraindications for thrombolysis
• Hemorrhagic stroke or stroke of unknown origin at any time
• Ischemic stroke in the preceding 6 months
• Central nervous system damage or neoplasms
• Recent major trauma/surgery/head injury in the preceding 3 weeks
• Gastrointestinal bleeding within the last month
• Known bleeding risk

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead
• Herlev and Gentofte Hospital: collaborator
• University Hospital Bispebjerg and Frederiksberg: collaborator
• Hillerod Hospital, Denmark: collaborator
• Copenhagen University Hospital, Hvidovre: collaborator

Study Sites (4)

Copenhagen University Hospital Gentofte

Gentofte Municipality, Capital Region, 2900, Denmark

Location

Copenhagen University Hospital Bispebjerg Hospital

Bispebjerg, DK2400, Denmark

Location

Copenhagen University Hospital Rigshospitalet

Copenhagen, DK2100, Denmark

Location

Copenhagen University Hospital, Herlev Gentofte Hospital

Herlev, DK2730, Denmark

Location

Related Publications (2)

• Kjaergaard J, Bang LE, Sonne-Holm E, Wiberg S, Holmvang L, Lassen JF, Sorensen R, Hofsten DE, Ulriksen PS, Jawad S, Palm P, Soe C, Ersboll MK, Boesgaard S, Moller JE, Thune JJ, Hassager C, Tilsted HH, Lonborg J, Egstrup M, Kristiansen OP, Seven E, Lindholm MG, Eskesen K, Fano S, Carlsen J. Randomized trial of low-dose -, ultrasound assisted thrombolysis or heparin for pulmonary embolism. Cardiovasc Res. 2026 Jan 29:cvag038. doi: 10.1093/cvr/cvag038. Online ahead of print.

  PMID: 41610160 DERIVED

• Kjaergaard J, Carlsen J, Sonne-Holm E, Wiberg S, Holmvang L, Lassen JF, Sorensen R, Hofsten D, Ulriksen PS, Jawad S, Palm P, Thune JJ, Hassager C, Kristiansen OP, Eskesen K, Fano S, Bang LE. A randomized trial of low-dose thrombolysis, ultrasound-assisted thrombolysis, or heparin for intermediate-high risk pulmonary embolism-the STRATIFY trial: design and statistical analysis plan. Trials. 2024 Dec 28;25(1):853. doi: 10.1186/s13063-024-08688-4.

  PMID: 39732696 DERIVED

MeSH Terms

Conditions

Pulmonary Embolism

Interventions

Tissue Plasminogen Activator; Powders; Solutions

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Embolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Biological Factors; Dosage Forms; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Primary endpoint will be assessed by assessor blinded to the intervention
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Sponsor, Primary investigator

Model Details: Randomized clinical trial with 1:1:1 allocation to treatment strata

Study Record Dates

• First Submitted: September 9, 2019
• First Posted: September 12, 2019
• Study Start: June 6, 2019
• Primary Completion: June 5, 2024
• Study Completion: November 30, 2024
• Last Updated: November 15, 2024

Record last verified: 2024-11

Locations

DK (4)