The classic website will no longer be available as of June 25, 2024. Please use the modernized ClinicalTrials.gov.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Low Dose Catheter Directed Thrombolysis for Acute Pulmonary Embolism (BETULA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03854266
Recruitment Status : Unknown
Verified April 2021 by University of Aarhus.
Recruitment status was:  Recruiting
First Posted : February 26, 2019
Last Update Posted : April 28, 2021
Sponsor:
Information provided by (Responsible Party):
University of Aarhus

Brief Summary:

BETULA trial will compare the efficacy of low dose catheter directed thrombolysis (CDT) to unfractioned heparin (UFH) in patients with intermediary-high risk pulmonary embolism (PE).

Patients (n=60) with acute intermediary-high risk PE will be randomized 1:1 to UFH (bolus 80 international units per kilo (IU/kg)) followed by 18 IU/kg/hour until activated partial thromboplastin time (APTT) is 2-2.5 of reference value) or CDT (4mg alteplase (r-tPA) per catheter, infusion over 2 hours) in an open label, outcome assessor blinded, randomized, controlled trial. Primary efficacy endpoint is improvement in right-/left ventricular ratio 24 hours after randomization. Secondary endpoints are 30 days mortality, recurrent PE, length of hospital stay and reduction in thrombus burden evaluated by pulmonary CT angio. Safety endpoints are minor and major bleedings.


Condition or disease Intervention/treatment Phase
Pulmonary Embolism Drug: Low dose alteplase Drug: Unfractionated heparin Device: Infusion catheter Phase 2

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Low Dose Catheter Directed Thrombolysis for Acute Intermediary-high Risk Pulmonary Embolism
Actual Study Start Date : March 10, 2020
Estimated Primary Completion Date : March 10, 2023
Estimated Study Completion Date : March 10, 2024


Arm Intervention/treatment
Experimental: Catheter directed thrombolysis
Low dose alteplase (4/8 milligram) will be infused over 2 hours locally in the pulmonary arteries at the site of the thrombus through an infusion catheter with sideholes (Unifuse, AngioDynamics, US)
Drug: Low dose alteplase
Low dose alteplase is 4 milligram per pulmonary artery (maximum dose 8 milligram) infused in the pulmonary arteries over 2 hours
Other Name: alteplase

Device: Infusion catheter
A sidehole catheter (Unifuse, AngioDynamics, US) catheter will be advanced to the pulmonary arteries to facilitate the catheter directed thrombolysis
Other Name: Unifuse

Active Comparator: Unfractionated heparin
Initial dose of unfractionated heparin is 80 international units per kilo (IU/kg) bolus followed by 18 IU/kg as continuous infusion with dose adjustment every 6 hours and once daily when activated partial thromboplastin time is 1.5-2.3 times control value.
Drug: Unfractionated heparin
Unfractioned heparin is administered in a peripheral vein with an initial dose of 80 international units per kilo (IU/kg) bolus followed by 18 IU/kg as continuous infusion with dose adjustment every 6 hours and once daily when activated partial thromboplastin time (APPT) is 1.5-2.3 times control value.
Other Name: heparin




Primary Outcome Measures :
  1. Right ventricle divided by left ventricular diameter (RV/LV ratio) [ Time Frame: 24 hours after intervention ]
    Measured on ECG gated contrast enhanced computed tomography


Secondary Outcome Measures :
  1. Reduction in thrombus burden [ Time Frame: 24 hours after intervention ]
    A modified miller index till be measured on ECG gated contrast enhanced computed tomography

  2. Thirty day mortality [ Time Frame: 30 days after intervention ]
    The number of patients that are decease within 30 days after the intervention will be assessed from the patient files.

  3. Length of hospital stay [ Time Frame: 3 months after intervention ]
    The length of hospital stay in days will be evaluated from the patient files

  4. Recurrent pulmonary embolism [ Time Frame: 3 months after intervention ]
    Number of patients with recurrent pulmonary embolism will be evaluated from the patient files

  5. Lung perfusion [ Time Frame: 24 hours after intervention ]
    Lung perfusion will be evaluated and quantified with dual energy computed tomography


Other Outcome Measures:
  1. Minor and major bleeding [ Time Frame: 24 hours after intervention ]
    Bleeding events will be recorded during the hospital stay during the daily rounds



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age > 17 and < 81 years
  • Debut of symptoms <14 days
  • Acute symptomatic Intermediate-high risk pulmonary embolism (PE, according to 2014 European Society of Cardiology guidelines) confirmed by computed tomography angiography (CTA) with the embolus located in at least one proximal lower lobe or main pulmonary artery.
  • Right-to-left ventricular dimension ratio >1.0 on CTA or trans-thoracic echocardiography (TTE)

Exclusion Criteria:

  • Significant bleeding risk or other contraindications to catheter directed thrombolysis (CDT) or unfractionated heparin*
  • Not possible to perform CDT within 48 hours after diagnosis
  • Pregnancy
  • Cardiac arrest requiring cardiopulmonary resuscitation
  • Life expectancy < 120 days
  • Altered mental status such that the patient is unable to provide informed consent
  • Suspected or known chronic thromboembolic pulmonary hypertension
  • Sustained hypertension (>180 mmHg systolic and/or >105 mmHg diastolic)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03854266


Contacts
Layout table for location contacts
Contact: Asger Andersen, MD, PhD +45-26363226 asger.andersen@clin.au.dk
Contact: Jens Erik Nielsen-Kudsk, MD, dMSc je.nielsen.kudsk@gmail.com

Locations
Layout table for location information
Denmark
Aarhus University Hospital, Dep. Cardiology Recruiting
Aarhus N, Denmark, 8200
Contact: Asger Andersen, MD, PhD    26363226    asgerandersen@gmail.com   
Contact: Jacob G Schultz, MD, PhD       jacobgschultz@gmail.com   
Sponsors and Collaborators
University of Aarhus
Investigators
Layout table for investigator information
Principal Investigator: Asger Andersen, MD, PhD Aarhus University Hospital
Publications:

Layout table for additonal information
Responsible Party: University of Aarhus
ClinicalTrials.gov Identifier: NCT03854266    
Other Study ID Numbers: 190580-0001
First Posted: February 26, 2019    Key Record Dates
Last Update Posted: April 28, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
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
Additional relevant MeSH terms:
Layout table for MeSH terms
Pulmonary Embolism
Embolism
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Heparin
Calcium heparin
Tissue Plasminogen Activator
Anticoagulants
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action