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

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ClinicalTrials.gov Identifier: NCT04088292
Recruitment Status : Recruiting
First Posted : September 12, 2019
Last Update Posted : November 18, 2023
Sponsor:
Collaborators:
Herlev and Gentofte Hospital
University Hospital Bispebjerg and Frederiksberg
Hillerod Hospital, Denmark
Copenhagen University Hospital, Hvidovre
Information provided by (Responsible Party):
Jesper Kjaergaard, Rigshospitalet, Denmark

Tracking Information
First Submitted Date  ICMJE September 9, 2019
First Posted Date  ICMJE September 12, 2019
Last Update Posted Date November 18, 2023
Actual Study Start Date  ICMJE June 6, 2019
Estimated Primary Completion Date June 5, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 11, 2019)
  • Reduction in Miller score comparing low dose thrombolysis and heparin alone groups [ Time Frame: 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 [ Time Frame: 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)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 11, 2019)
  • Incidence of bleeding complications [ Time Frame: Until hospital discharge, on average 1 week ]
    Bleeding complications (major and minor bleeding complication according the TIMI classification)
  • Length of stay of index admission [ Time Frame: End of study, expected to be 2 years ]
    Duration of index admission, including hospital based rehabilitation
  • Dyspnea index by visual analogue scale [ Time Frame: End of study, expected to be 2 years ]
    Dyspnea index (Visual analog scale) after 48-96 h and after 3 months
  • Change in oxygen supplement (FiO2) [ Time Frame: at 48 to 96 hours post randomization ]
    FiO2 (in %)
  • Mortality rate [ Time Frame: End of study, expected to be 2 years ]
    Mortality in the three groups (log-rank), and hazard ratio in multivariable analysis using the UFH/LMWH as reference
  • Reduction in D-dimer values [ Time Frame: at 48 to 96 hours post randomization ]
    Reduction in D-dimer from baseline to 48-96h post randomization
  • Incidence of Pulmonary Hypertension [ Time Frame: 3 months follow-up ]
    Incidence of TR gradient > 40 mmHg at 3 months follow-up echocardiography
  • Reduction in troponin levels [ Time Frame: at 48 to 96 hours post randomization ]
    Relative reduction in TnI/T from baseline to 48-96 h post intervention
  • Reduction in NT-pro-BNP levels [ Time Frame: 3 months follow-up ]
    Reduction in NT-pro-BNP at 48-96 hours and 3 months
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Low Dose Thrombolysis, Ultrasound Assisted Thrombolysis or Heparin for Intermediate High Risk Pulmonary Embolism
Official Title  ICMJE Low Dose Thrombolysis, Ultrasound Assisted Thrombolysis or Heparin for Intermediate High Risk Pulmonary Embolism
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
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Randomized clinical trial with 1:1:1 allocation to treatment strata
Masking: Single (Outcomes Assessor)
Masking Description:
Primary endpoint will be assessed by assessor blinded to the intervention
Primary Purpose: Treatment
Condition  ICMJE Pulmonary Embolism
Intervention  ICMJE
  • 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)
Study Arms  ICMJE
  • Active Comparator: USAT + low dose thrombolysis
    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
    Interventions:
    • Drug: Alteplase 20 Mg Powder for Solution for Injection Vial
    • Device: Ultrasound assisted Thrombolysis
  • Active Comparator: Low dose thrombolysis
    Intravenous low dose thrombolysis (20 mg of rtPA, Alteplase) over 6 hours plus UFH or low molecular weight heparin (LMWH).
    Intervention: Drug: Alteplase 20 Mg Powder for Solution for Injection Vial
  • No Intervention: Heparin alone
    UFH or low molecular weight heparin (LMWH) only (with option for conventional thrombolysis according to local protocols for hemodynamic deterioration)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 11, 2019)		 210
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 31, 2024
Estimated Primary Completion Date June 5, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jesper Kjærgaard, MD PhD DMSc +45 35450969 jesper.kjaergaard.05@regionh.dk
Contact: Lia Bang, MD PhD +45 35453545 lia.evi.bang@regionh.dk
Listed Location Countries  ICMJE Denmark
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04088292
Other Study ID Numbers  ICMJE STRATIFY-1
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Plan Description: Main trial database
Current Responsible Party Jesper Kjaergaard, Rigshospitalet, Denmark
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Rigshospitalet, Denmark
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE
  • Herlev and Gentofte Hospital
  • University Hospital Bispebjerg and Frederiksberg
  • Hillerod Hospital, Denmark
  • Copenhagen University Hospital, Hvidovre
Investigators  ICMJE Not Provided
PRS Account Rigshospitalet, Denmark
Verification Date November 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP