Project Details
Projekt
Pulmonary Embolism International Thrombolysis Study (PEITHO) Study 3: A reduced dose of intravenous thrombolytic treatment for patients with intermediate high-risk acute pulmonary embolism
Applicant
Professor Dr. Stavros Konstantinides
Subject Area
Cardiology, Angiology
Term
since 2020
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 401833708
Venous thromboembolism (VTE), presenting as deep vein thrombosis or pulmonary embolism (PE), is globally the third most frequent acute cardiovascular syndrome behind myocardial infarction and stroke. As the risk of VTE doubles with each decade of life after the age of 40, an increasing number of individuals in ageing societies will be diagnosed with PE in the years to come. Intravenously administered thrombolysis is the most practicable (available, fast and affordable) form of ‘reperfusion’ therapy for acute PE. Thrombolysis is highly effective in rapidly opening the occluded pulmonary arteries and their branches in severe PE. Currently however, primary systemic thrombolytic therapy is recommended only for PE patients with cardiogenic shock in view of its bleeding risk. The first Pulmonary Embolism Thrombolysis (PEITHO) trial examined the impact of systemic full-dose thrombolysis on the early outcome of patients with intermediate-risk PE, defined by a normotensive haemodynamic status, right ventricular dysfunction on imaging tests, and elevated cardiac troponin levels. The combined primary efficacy outcome was significantly reduced in the thrombolysis arm, but there was a substantial increase in intracranial and other major bleeding. The proposed PEITHO-III is an investigator-initiated, academically sponsored, randomised, placebo-controlled, double-blind, multinational, multicentre therapeutic trial including two-year follow-up. Its objectives are 1) to improve the safety of intravenous thrombolysis by testing a reduced dose of the approved thrombolytic agent alteplase, and 2) to advance the concept of intermediate-high risk PE, better identifying patients at risk who may need, and benefit from, thrombolysis. Patients with acute PE will be included in PEITHO-III if they have no overt haemodynamic instability but present with a combination of clinical (identified on the basis of PEITHO-I), imaging (echocardiography, computed tomography) and laboratory (elevated cardiac troponin levels) parameters indicating an elevated risk of early (30-day) death, haemodynamic collapse, or PE recurrence (the primary outcome). Experimental intervention will consist of alteplase given as a 15 min intravenous infusion at a dosage of 0.6 mg/kg, with a total dose not exceeding 50 mg; control intervention, of alteplase placebo given at the same dosage and infusion rate. Both groups will receive therapeutic anticoagulation. Our hypothesis is that reduced-dose thrombolytic treatment will result in significant reduction in the primary outcome compared to heparin alone, and that this reduction will be obtained without a significant increase in intracranial or other life-threatening bleeding as was the case with full-dose thrombolysis in previous trials. The impact on long-term outcomes and PE sequelae will also be investigated.
DFG Programme
Clinical Trials
International Connection
France
