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PEITHO-3 - A reduced dose of thrombolytic treatment for patients with intermediate high-risk acute pulmonary embolism: a randomized controlled trial
EU CTIS ID: 2024-511321-54-00
What this study is testing
To assess the efficacy of reduced dose thrombolytic therapy in patients with acute intermediate-high-risk pulmonary embolism at day 30.
- Therapeutic confirmatory (Phase III)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- 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 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: systolic blood pressure ≤ 110 mm Hg over at least 15 minutes upon enrolment 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 mm Hg and adequate organ perfusion without catecholamine infusion respiratory rate > 20/min or oxygen saturation on pulse oximetry (SpO2) < 90% (or partial arterial oxygen pressure < 60 mm Hg) at rest while breathing room air 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
You likely can't join if
- Hemodynamic instability, defined by at least one of the following criteria [1] - cardiac arrest; - obstructive shock, defined as: (i) systolic BP < 90 mm Hg, or vasopressors required to achieve a SBP ≥90 mm Hg despite an adequate filling status; and (ii) end-organ hypoperfusion (altered mental status; cold, clammy skin; oliguria/anuria; increased serum lactate); - isolated persistent hypotension (systolic BP < 90 mm Hg, or a systolic pressure drop ≥ 40 mm Hg for > 15 min), if not caused by new-onset arrhythmia, hypovolemia, or sepsis
- Previous enrolment in this study
- Known hypersensitivity to alteplase, gentamicin (a residue of the Actilyse®/Activase® (only for Canada) manufacturing process present in trace amounts), any of the excipients of Actilyse®/Activase® (only for Canada), or low-molecular weight heparin
- 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
See the full eligibility criteria
Who can join
- 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 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: systolic blood pressure ≤ 110 mm Hg over at least 15 minutes upon enrolment 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 mm Hg and adequate organ perfusion without catecholamine infusion respiratory rate > 20/min or oxygen saturation on pulse oximetry (SpO2) < 90% (or partial arterial oxygen pressure < 60 mm Hg) at rest while breathing room air 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 receives 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
What rules you out
- Hemodynamic instability, defined by at least one of the following criteria [1] - cardiac arrest; - obstructive shock, defined as: (i) systolic BP < 90 mm Hg, or vasopressors required to achieve a SBP ≥90 mm Hg despite an adequate filling status; and (ii) end-organ hypoperfusion (altered mental status; cold, clammy skin; oliguria/anuria; increased serum lactate); - isolated persistent hypotension (systolic BP < 90 mm Hg, or a systolic pressure drop ≥ 40 mm Hg for > 15 min), if not caused by new-onset arrhythmia, hypovolemia, or sepsis
- Previous enrolment in this study
- Known hypersensitivity to alteplase, gentamicin (a residue of the Actilyse®/Activase® (only for Canada) manufacturing process present in trace amounts), any of the excipients of Actilyse®/Activase® (only for Canada), or low-molecular weight heparin
- 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
- 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
- Known previous immune heparin-induced thrombocytopenia
- Known severe liver disease (grade ≥ 3)1 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
- 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.
- 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
The study team makes the final eligibility decision.
Where it's taking place
- Serbia
- Canada
- Switzerland
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18-64 years, 65+ years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Serbia; Canada; Switzerland. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.