Low dose catheter directed thrombolytic therapy for patients suffering from acute pulmonary embolism.

Low dose catheter directed thrombolysis for acute intermediary-high risk pulmonary embolism. - BETULA

Status

Active, not recruiting

Phases

Phase 4

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2018-003564-31-DK

Enrollment

Registered

2019-02-27

Start date

2020-01-16

Completion date

Unknown

Last updated

2025-02-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Acute intermediary-high risk pulmonary embolism MedDRA version: 21.0 Level: PT Classification code 10037377 Term: Pulmonary embolism System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Interventions

Trade Name: Actilyse Pharmaceutical Form: Powder and solvent for solution for injection/infusion INN or Proposed INN: ALTEPLASE CAS Number: 105857-23-6 Concentration unit: mg milligram(s) Concentratio

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: - Age > 17 and 1.0 on contrast enhanced computed tomography or transthoracic echocardiography. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40

Exclusion criteria

Exclusion criteria: - Significant bleeding risk or other contraindications to catheter directed trombolysis or unfractioned heparin.* - Not possible to perform catheter directed trombolysis within 48 h after diagnosis - Known pregnancy or positive urine hCG screening test in fertile women** - Cardiac arrest requiring cardiopulmonary resuscitation - Life expectancy 180 mmHg systolic and/or >105 mmHg diastolic) *Treated with thrombolytics for the index ** Fertile women will be screened for pregnancy with a blood hCG screening test before inclusion if they are not on any contraceptives.

Design outcomes

Primary

Measure	Time frame
Main Objective: To investigate if low dose catheter directed fibrinolysis for 2 h is superior to unfractioned heparin with regards to unloading the right ventricle in acute intermediate-high risk pulmonary embolism. ;Secondary Objective: Not applicable;Primary end point(s): improvement in right-to-left ventricular ratio (RV/LV-ratio) measured on an ecg gated CTA in the transverse four chamber view 1 cm above the atrio-ventricular plane as used by others in similar studies. All analysis will be performed by a core facility with a trained investigator, not affiliated to the study protocol and blinded to the treatment. ;Timepoint(s) of evaluation of this end point: A CTA will be performed after inclusion, but before randomization and this will be repeated 24h after randomization.	—

Measure

Time frame

Main Objective: To investigate if low dose catheter directed fibrinolysis for 2 h is superior to unfractioned heparin with regards to unloading the right ventricle in acute intermediate-high risk pulmonary embolism. ;Secondary Objective: Not applicable;Primary end point(s): improvement in right-to-left ventricular ratio (RV/LV-ratio) measured on an ecg gated CTA in the transverse four chamber view 1 cm above the atrio-ventricular plane as used by others in similar studies. All analysis will be performed by a core facility with a trained investigator, not affiliated to the study protocol and blinded to the treatment. ;Timepoint(s) of evaluation of this end point: A CTA will be performed after inclusion, but before randomization and this will be repeated 24h after randomization.

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Secondary

Measure	Time frame
Secondary end point(s): Efficacy Endpoints: Reduction in thrombus burden The pre and post CTAs will be analyzed using the modified Miller score to estimate the change in clot burden between treatment groups. The analysis will be performed by a core facility with a trained investigator, not affiliated to the study protocol and blinded to the treatment. Lung perfusion The CT scan will be recorded using a dual energy CT technique which will allow for quantification of lung perfusion. The analysis will be performed by a core facility with a trained investigator, not affiliated to the study protocol and blinded to the treatment. Thirty day mortality Thirty day mortality will be obtained from the electronic patient files. Length of hospital stay The length of hospital stay is at the discretion of the treating physician and will be registered in the CRF based on the electronic patient file. Recurrent PE Information regarding recurrent PE will be obtained from the patient file from the routine follow-up clinical visit 90 days after discharge. Minor and major bleeding Minor bleeding will be classified as clinical overt bleeding that does not fulfill the criteria of a major bleeding. Major bleeding is defined as overt bleeding that involves a critical site (intramuscular with compartment syndrome, intracranial, intraspinal, retropretoneal, intraocular, intraarticular or pericardial), or is associated with a fall in hemoglobin of >2g/dl or the need of transfusion with 2 or more units of red blood cells. Bleeding events will be recorded during the hospital stay during the daily rounds. Exhaled breath condensate Protein analysis for biomarkers of right heart strain, inflammation and coagulation will be analyzed in exhaled breath condensate (EBC). EBC will be collected by use of the commercially available RTube system after inclusion and repeated after treatment and analyzed by label free quantitative nano liquid chromatography - tandem mass spectrometry. Serious Advers	—

Measure

Time frame

Secondary end point(s): Efficacy Endpoints: Reduction in thrombus burden The pre and post CTAs will be analyzed using the modified Miller score to estimate the change in clot burden between treatment groups. The analysis will be performed by a core facility with a trained investigator, not affiliated to the study protocol and blinded to the treatment. Lung perfusion The CT scan will be recorded using a dual energy CT technique which will allow for quantification of lung perfusion. The analysis will be performed by a core facility with a trained investigator, not affiliated to the study protocol and blinded to the treatment. Thirty day mortality Thirty day mortality will be obtained from the electronic patient files. Length of hospital stay The length of hospital stay is at the discretion of the treating physician and will be registered in the CRF based on the electronic patient file. Recurrent PE Information regarding recurrent PE will be obtained from the patient file from the routine follow-up clinical visit 90 days after discharge. Minor and major bleeding Minor bleeding will be classified as clinical overt bleeding that does not fulfill the criteria of a major bleeding. Major bleeding is defined as overt bleeding that involves a critical site (intramuscular with compartment syndrome, intracranial, intraspinal, retropretoneal, intraocular, intraarticular or pericardial), or is associated with a fall in hemoglobin of >2g/dl or the need of transfusion with 2 or more units of red blood cells. Bleeding events will be recorded during the hospital stay during the daily rounds. Exhaled breath condensate Protein analysis for biomarkers of right heart strain, inflammation and coagulation will be analyzed in exhaled breath condensate (EBC). EBC will be collected by use of the commercially available RTube system after inclusion and repeated after treatment and analyzed by label free quantitative nano liquid chromatography - tandem mass spectrometry. Serious Advers

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Countries

Denmark

Contacts

Public ContactAsger Andersen

Aarhus University Hospital

asger.andersen@clin.au.dk

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026