NCT04430569

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

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 800 (estimated)
• Sponsor: Assistance Publique - Hôpitaux de Paris · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

In patients with intermediate-risk pulmonary embolism, full-dose thrombolytic treatment was associated with a reduction in the combined risk of hemodynamic instability or death but was also associated with an increased risk of major and intracranial bleeding. Previous studies suggest that reduced dose of thrombolytic treatment may be as effective as the full dosage, but with a decreased risk of life-threatening bleeding. In this study, we will assess the efficacy and safety of a reduced dosage of thrombolytic therapy in patients with intermediate-high-risk acute pulmonary embolism. The study is a randomized, placebo-controlled, double blind, multicenter, multinational trial with long-term follow-up. Patients fulfilling the inclusion criteria and without any of the exclusion criteria will be randomized within 6 hours after the investigator had confirmed the diagnosis. Patients will receive: * Alteplase (if randomized in the experimental group) or placebo (if randomized in the reference group) given within 30 minutes of randomization as a 15 min intravenous infusion at a dosage of 0.6 mg/kg with a total dose not exceeding 50 mg. * Parenteral anticoagulation with low molecular weight heparin, unfractionnated heparin or fondaparinux Primary objective is to assess the efficacy of reduced dose thrombolytic therapy in patients with acute intermediate-high-risk pulmonary embolism at day 30. Secondary objectives are: 1. To assess the safety of reduced dose thrombolytic therapy in patients with intermediate-high-risk acute pulmonary embolism at day 30 2. To assess the net clinical benefit of reduced dose thrombolytic therapy in patients with intermediate-high-risk acute pulmonary embolism at day 30 3. To assess the effect of reduced dose thrombolytic therapy on overall mortality of patients with intermediate-high-risk acute pulmonary embolism at day 30 4. To assess the effect of reduced dose thrombolytic therapy on long-term mortality, functional impairment, residual right ventricular dysfunction and chronic thromboembolic pulmonary hypertension at 6 months and 2 years 5. To assess the effect of reduced-dose thrombolytic therapy on utilization of health care resources at day 30 and day 180

Conditions

• Pulmonary Embolism

Interventions

Type	Name	Description
DRUG	Alteplase	Alteplase single intravenous infusion of 0.6 mg/kg of estimated bodyweight with a maximum of 50 mg given over 15 minutes.
DRUG	Placebo	Placebo single intravenous infusion of 0.6 mg/kg of estimated bodyweight with a maximum of 50 mg given over 15 minutes.

Timeline

• Start date: 2021-08-04
• Primary completion: 2026-09-01
• Completion: 2028-08-01
• First posted: 2020-06-12
• Last updated: 2025-05-16

Locations

98 sites across 14 countries: Austria, Belgium, Canada, France, Germany, Italy, Netherlands, Poland, Portugal, Romania, Serbia, Slovenia, Spain, Switzerland