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Assessing reduced dose thrombolytic therapy for pulmonary embolism

A Reduced Dose of Thrombolytic Treatment for Patients With Intermediate High-risk Acute Pulmonary Embolism: a Randomized Controled Trial

Phase 3 Interventional Assistance Publique - Hôpitaux de Paris · NCT04430569

This study is testing if a lower dose of a clot-busting drug, combined with another medication, can safely help people with serious pulmonary embolism feel better.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment800 (estimated)
Ages18 Years and up
SexAll
SponsorAssistance Publique - Hôpitaux de Paris Academic / other
Locations98 sites (Graz and 97 other locations)
Trial IDNCT04430569 on ClinicalTrials.gov

What this trial studies

This study evaluates the efficacy and safety of a reduced dose of thrombolytic therapy combined with low-molecular-weight heparin in patients diagnosed with intermediate-high-risk acute pulmonary embolism. Participants will be randomly assigned to receive either the thrombolytic agent alteplase or a placebo within 30 minutes of randomization. The primary goal is to determine the effectiveness of this reduced dosage at 30 days post-treatment, while secondary objectives focus on assessing safety outcomes. The study is designed as a randomized, placebo-controlled, double-blind, multicenter, multinational trial with long-term follow-up.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with objectively confirmed acute pulmonary embolism and elevated risk of early death or hemodynamic collapse.

Not a fit: Patients with low-risk pulmonary embolism or those who do not meet the inclusion criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a safer treatment option for patients with acute pulmonary embolism, reducing the risk of life-threatening bleeding.

How similar studies have performed: Previous studies have suggested that reduced doses of thrombolytic therapy may be effective, indicating potential for success in this novel approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Age 18 years or older
* Objectively confirmed acute PE with first symptoms occurring 2 weeks or less before randomization. Objective confirmation is based on at least one of the following criteria: (a) at least one segmental ventilation-perfusion mismatch on lung scanning; (b) a spiral computed tomography pulmonary angiography or pulmonary angiography showing a filling defect or an abrupt obstruction of a segmental or more proximal pulmonary artery
* Acute PE confirmed within 24 hours prior to randomization
* Elevated risk of early death, or of hemodynamic collapse, or PE recurrence, indicated by at least one of the following criteria: (a) systolic blood pressure ≤ 110 mm Hg over at least 15 minutes upon enrolment, (b) temporary need for fluid resuscitation and/or treatment with low-dose catecholamines, provided that the patient could be stabilized within 2 hours of admission and maintains SBP of ≥ 90 mmHg and adequate organ perfusion without catecholamine infusion; (c) respiratory rate \> 20/min or oxygen saturation on pulse oximetry SpO2 \<90% o(or partial arterial oxygen pressure \< 60 mm Hg) at rest while breathing room air, (d) documented history of chronic symptomatic heart failure
* Right ventricular dysfunction indicated by RV/LV diameter ratio \>1.0 on echocardiography apical four-chamber or subcostal four-chamber view or on Computed Tomography Pulmonary Angiography (transverse plane)
* Serum troponin I or T concentration above the upper limit of local normal using a high-sensitivity assay
* Ability to randomize the patient within 6 hours after the investigator receives the results of the second of the two criteria for RV dysfunction (RV/LV diameter ratio \>1.0) and myocardial injury (serum troponin I or T concentration above the upper limit of local normal), whichever comes latest.
* Signed informed consent form

Exclusion Criteria:

* Hemodynamic instability
* Active bleeding
* History of non-traumatic intracranial bleeding, any time
* Acute ischemic stroke or transient ischemic attack (TIA) within the previous 6 months
* Known central nervous system neoplasm/metastasis
* Neurologic, ophthalmologic, abdominal, cardiac, thoracic, vascular or orthopedic surgery or trauma within 3 previous weeks
* Platelet count \< 100 G/L
* INR \> 1.4. If INR not available: prothrombin time ratio \< 60%. If both INR and prothrombin time ratio are measured, INR is relevant for the assessment of this criterion.
* Treatment with antiplatelet agents other than (a) acetylsalicylic acid (ASA) ≤ 100 mg once daily or (b) clopidogrel 75 mg once daily or (c) a single loading dose of ASA or clopidogrel. Dual antiplatelet therapy (ASA + clopidogrel) is not allowed.
* Any direct oral anticoagulant within 12 hours of inclusion
* Uncontrolled hypertension defined by SBP \> 180 mm Hg at the time of inclusion
* Known pericarditis or endocarditis
* Known significant bleeding risk according to the investigator's judgement
* Administration of thrombolytic agents within the previous 4 days
* Vena cava filter insertion or pulmonary thrombectomy within the previous 4 days
* Current participation in another interventional clinical study
* Previous enrolment in this study
* Known hypersensitivity to alteplase, gentamicin (a residue of the Actilyse® manufacturing process present in trace amounts), any of the excipients of Actilyse®, or low-molecular weight heparin (LMWH)
* Known previous immune heparin-induced thrombocytopenia
* Known severe liver disease (grade ≥ 3) including liver failure, cirrhosis, portal hypertension (esophageal varices) and active hepatitis
* Acute symptomatic pancreatitis
* Gastrointestinal ulcers or esophageal varices, documented within the past 3 months
* Known arterial aneurysm, arterial or venous malformations
* Pregnancy or parturition within the previous 30 days or current breastfeeding.
* Women of childbearing potential who do not have a negative pregnancy test at the inclusion visit and do not use one of the following methods of birth control: hormonal contraception or intrauterine device or bilateral tubal occlusion
* Any other condition that the investigator feels would place the patient at increased risk upon start of the investigational treatment
* Life expectancy of less than 6 months or inability to complete 6-month follow-up.
* Patient under legal protection

Where this trial is running

Graz and 97 other locations

+48 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Pulmonary EmbolismIntermediate-high-risk acute pulmonary embolismThrombolysis
Last reviewed 2026-06-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.