RecruitingPhase 3NCT04430569
Pulmonary Embolism International THrOmbolysis Study-3
A Reduced Dose of Thrombolytic Treatment for Patients With Intermediate High-risk Acute Pulmonary Embolism: a Randomized Controled Trial
Sponsor
Assistance Publique - Hôpitaux de Paris
Enrollment
800 participants
Start Date
Aug 4, 2021
Study Type
INTERVENTIONAL
Conditions
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.
Eligibility
Min Age: 18 Years
Inclusion Criteria8
- 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 Criteria28
- 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
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Interventions
DRUGAlteplase
Alteplase single intravenous infusion of 0.6 mg/kg of estimated bodyweight with a maximum of 50 mg given over 15 minutes.
DRUGPlacebo
Placebo single intravenous infusion of 0.6 mg/kg of estimated bodyweight with a maximum of 50 mg given over 15 minutes.
Locations(98)
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NCT04430569
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