NCT03854266: BETULA

Low Dose Catheter Directed Thrombolysis for Acute Pulmonary Embolism

Status unknown Phase 2 Last updated 28 April 2021

What this trial tests

Phase 2 trial testing Low dose alteplase in Pulmonary Embolism in 60 participants. Status unknown.

Timeline

10 March 2020

Primary endpoint
10 March 2023

10 March 2024

Quick facts

Lead sponsor	University of Aarhus
Phase	Phase 2
Status	Status unknown
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	single
Primary purpose	treatment
Enrollment	60
Start date	10 March 2020
Primary completion	10 March 2023
Estimated completion	10 March 2024
Sites	1 location across Denmark

Drugs / interventions tested

• Low dose alteplase — full drug profile →
• Unfractionated heparin — full drug profile →
• Infusion catheter

Conditions studied

• Pulmonary Embolism — all drugs for Pulmonary Embolism →

Sponsor

University of Aarhus

Who can join

Adults 18 to 80, any sex, with Pulmonary Embolism. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Percutaneous treatment options for acute pulmonary embolism: a clinical consensus statement by the ESC Working Group on Pulmonary Circulation and Right Ventricular Function and the European Association of Percutaneous Cardiovascular Interventions.
   Pruszczyk P, Klok FA, Kucher N, Roik M, et al · · 2022 · cited 146× · PMID 36112184 · DOI 10.4244/eij-d-22-00246
2. Thrombolytic therapy for pulmonary embolism.
   Zuo Z, Yue J, Dong BR, Wu T, et al · · 2021 · cited 27× · PMID 33857326 · DOI 10.1002/14651858.cd004437.pub6
3. Catheter-directed therapies for the treatment of high risk (massive) and intermediate risk (submassive) acute pulmonary embolism.
   Harvey JJ, Huang S, Uberoi R. · · 2022 · cited 26× · PMID 35938605 · DOI 10.1002/14651858.cd013083.pub2
4. Outcomes of catheter-directed interventions in high-risk pulmonary embolism-a retrospective analysis.
   Einarsson F, Sandström C, Svennerholm K, Oras J, et al · · 2021 · cited 4× · PMID 33245785 · DOI 10.1111/aas.13753
5. When should we involve interventional radiology in the management of acute pulmonary embolism?
   Barca-Hernando M, Jara-Palomares L. · · 2023 · cited 3× · PMID 37719239 · DOI 10.1183/20734735.0085-2023
6. Endovascular management of intermediate-risk pulmonary embolism: evidence, outstanding questions, drivers of utilization, and the horizon.
   Shahriar AA, Paul J, Cifu A. · · 2025 · cited 1× · PMID 40567595 · DOI 10.1093/ehjopen/oeaf071
7. Advancements in Pulmonary Embolism Management: Current Approaches and Future Directions.
   Banfi C, Montonati C, Ielasi A, Assouline B, et al · · 2025 · PMID 41356320 · DOI 10.31083/rcm44614
8. Catheter-Based Therapies in Acute Pulmonary Embolism-Mortality and Safety Outcomes: A Systematic Review and Meta-Analysis.
   Zoumpourlis P, Mangeshkar S, Chi KY, Varrias D, et al · · 2025 · PMID 40565913 · DOI 10.3390/jcm14124167