Pulmonary Embolism International THrOmbolysis Study-3

Launched by ASSISTANCE PUBLIQUE - HÔPITAUX DE PARIS · Jun 10, 2020

Keywords

ClinConnect Summary

The Pulmonary Embolism International THrOmbolysis Study-3 is a clinical trial designed to evaluate the effectiveness and safety of a lower dose of a special medication called thrombolytic therapy, used alongside a blood thinner called low-molecular-weight heparin, for patients suffering from a serious condition known as pulmonary embolism (PE). This condition occurs when a blood clot blocks a blood vessel in the lungs, which can be life-threatening. In this study, half of the participants will receive the thrombolytic treatment, while the other half will receive a placebo, which is a treatment that has no active ingredients.

To be eligible for the trial, participants must be at least 18 years old and have a confirmed diagnosis of acute pulmonary embolism with symptoms appearing within the last two weeks. They should also have specific health indicators that suggest they are at moderate to high risk for serious complications from PE. Participants will need to provide informed consent and will be monitored closely throughout the study. This research is currently recruiting individuals of all genders who meet the criteria, and it aims to help improve treatment options for people facing this challenging condition.

Gender

ALL

Eligibility 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