Reduced-Dose Intravenous Thrombolysis for Acute Intermediate-High-risk Pulmonary Embolism: Rationale and Design of the Pulmonary Embolism International THrOmbolysis (PEITHO)-3 trial.
Olivier SanchezAnaïs Charles-NelsonWalter AgenoAlexandru GrigoreanHarald BinderGilles ChatellierDaniel DuerschmiedKlaus EmpenMelanie FerreiraPhilippe GirardMenno V HuismanDavid JiménezSandrine KatsahianMatija KozakMareike LankeitNicolas MeneveauPiotr PruszczykAntoniu PetrisMarc RighiniStephan RosenkranzSebastian SchellongBranislav StefanovicPeter VerhammeKerstin de WitEric VicautAndreas ZirlikStavros V KonstantinidesGuy Meyernull nullPublished in: Thrombosis and haemostasis (2021)
Intermediate-high-risk pulmonary embolism (PE) is characterized by right ventricular (RV) dysfunction and elevated circulating cardiac troponin levels despite apparent hemodynamic stability at presentation. In these patients, full-dose systemic thrombolysis reduced the risk of hemodynamic decompensation or death but increased the risk of life-threatening bleeding. Reduced-dose thrombolysis may be capable of improving safety while maintaining reperfusion efficacy. The Pulmonary Embolism International THrOmbolysis (PEITHO)-3 study (ClinicalTrials.gov Identifier: NCT04430569) is a randomized, placebo-controlled, double-blind, multicenter, multinational trial with long-term follow-up. We will compare the efficacy and safety of a reduced-dose alteplase regimen with standard heparin anticoagulation. Patients with intermediate-high-risk PE will also fulfill at least one clinical criterion of severity: systolic blood pressure ≤110 mm Hg, respiratory rate >20 breaths/min, or history of heart failure. The primary efficacy outcome is the composite of all-cause death, hemodynamic decompensation, or PE recurrence within 30 days of randomization. Key secondary outcomes, to be included in hierarchical analysis, are fatal or GUSTO severe or life-threatening bleeding; net clinical benefit (primary efficacy outcome plus severe or life-threatening bleeding); and all-cause death, all within 30 days. All outcomes will be adjudicated by an independent committee. Further outcomes include PE-related death, hemodynamic decompensation, or stroke within 30 days; dyspnea, functional limitation, or RV dysfunction at 6 months and 2 years; and utilization of health care resources within 30 days and 2 years. The study is planned to enroll 650 patients. The results are expected to have a major impact on risk-adjusted treatment of acute PE and inform guideline recommendations.
Keyphrases
- pulmonary embolism
- inferior vena cava
- atrial fibrillation
- heart failure
- blood pressure
- end stage renal disease
- double blind
- healthcare
- mycobacterium tuberculosis
- placebo controlled
- newly diagnosed
- study protocol
- clinical trial
- chronic kidney disease
- prognostic factors
- ejection fraction
- phase ii
- phase iii
- liver failure
- drug induced
- peritoneal dialysis
- venous thromboembolism
- left ventricular
- oxidative stress
- metabolic syndrome
- patient reported outcomes
- acute myocardial infarction
- high dose
- acute coronary syndrome
- heart rate
- type diabetes
- computed tomography
- respiratory failure
- skeletal muscle
- rectal cancer
- low dose
- phase ii study
- brain injury
- blood glucose
- locally advanced