A reduced dose of thrombolytic treatment for patients with intermediate-high-risk acute pulmonary embolism

Phase 1

• Conditions: Intermediate-high-risk acute pulmonary embolism; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2018-000816-96-AT
• Lead Sponsor: Assistance Publique – Hôpitaux de Paris, Clinical Research and Innovation Delegation (DRCI)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2020-10-12
• Last Update Posted: 26 August 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 650

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 (CTPA) or selective 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 (SBP) = 110 mm Hg over at least 15 minutes upon enrolment, (b) temporary need for fluid resuscitation and/or treatment with low dose catecholamines because of arterial hypotension at presentation, 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 SpO2 <90% (or partial arterial oxygen pressure < 60 mmHg) at rest while breathing room air, (d) documented history of chronic symptomatic heart failure defined as previous diagnosis of heart failure (i.e. heart failure with reduced, moderately reduced or preserved ejection fraction) or treatment for heart failure at any time during the past 12 months;
• RV dysfunction indicated by RV/LV diameter ratio >1.0 on echocardiography apical four- chamber or subcostal four-chamber view or on CTPA (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 had received the result 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 the latest.
• Signed informed consent form
• [France]: Patient insured under a social security system
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 586
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 64

Exclusion Criteria

• Hemodynamic instability, defined by at least one of the following criteria
- cardiac arrest;
- obstructive shock, defined as: (i) SBP < 90 mmHg, or vasopressors required to achieve a SBP = 90 mmHg despite an adequate filling status; and (ii) end-organ hypoperfusion (altered mental status; cold, clammy skin; oliguria/anuria; increased serum lactate);
- isolated persistent hypotension (SBP < 90 mmHg, or a systolic pressure drop = 40 mm Hg for > 15 min), if not caused by new-onset arrhythmia, hypovolemia, or sepsis
• 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 the previous 3 weeks
• Platelet count < 100 x 109/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 anti-platelet 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
• [Italy and the Netherlands] Participation in another interventional clinical study within 30 days from the inclusion
• [All countries except Italy and the Netherlands]
• 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 thrombo-cytepenia
• 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 in the investigator's opinion 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified