Pulmonary Embolism International THrOmbolysis Study-3

• Status: Not yet recruiting
• Trial end date: 2027-09-01
• Target enrollment: 0
• Participant gender: All

Summary

In this study, we will assess the efficacy and safety of a reduced dose of thrombolytic therapy given in addition to low-molecular-weight heparin in patients with intermediate-high-risk acute pulmonary embolism. Half of participants will receive thrombolytic treatment, while the other half will receive a placebo.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Boehringer Ingelheim; Canadian Institutes of Health Research (CIHR); Johannes Gutenberg University Mainz; Life Sciences Research Partners (D Collen Research Foundation); University Medical Center of the Johannes Gutenberg University Mainz, Germany
• Treatments: Tissue Plasminogen Activator

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

• Objective confirmation of acute PE within the past 24 hours

• 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) history of chronic 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-sensitive assay

• Patient should be randomized within 6 hours after the investigator receives the results of the imaging test(s) confirming right ventricular dysfunction (RV/LV diameter ratio >1.0) and the laboratory tests showing a serum troponin I or T concentration above the upper limit of local normal, whichever comes latest.

• Signed informed consent

Exclusion Criteria:

• Hemodynamic instability

• Active bleeding

• History of non-traumatic intracranial bleeding, any time

• Acute ischemic stroke within 6 months

• Known central nervous system neoplasm/metastasis

• Neurologic, ophthalmologic, abdominal, cardiac, thoracic, vascular or orthopedic surgery or trauma within 3 weeks

• Platelet count < 100 G/L

• INR > 1.4

• 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 > 180/90 mm Hg at the time of inclusion

• Known pericarditis or endocarditis

• Known significant bleeding risk according to the physician'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

• 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 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.