Optimal Time for Reperfusion in Acute Pulmonary Embolism (OPTIRAPE)

Pulmonary embolism (PE) is the third leading cause of cardiovascular mortality worldwide. Current guidelines recommend early reperfusion for high-risk and intermediate-high-risk PE, yet systemic thrombolysis and percutaneous therapies are frequently underutilized, and no specific timing for reperfusion is defined, unlike in acute myocardial infarction or ischemic stroke. As most PE-related in-hospital deaths occur within the first hours and thrombus composition changes over time, defining an optimal reperfusion time window may improve survival and prevent hemodynamic deterioration. We therefore propose a national, multicenter, prospective observational study to evaluate the prognostic impact of reperfusion timing, using systemic thrombolysis or catheter-directed therapies, on in-hospital mortality and haemorrhagic or cardiovascular complications.

Study Overview

• Status: Recruiting
• Conditions: Pulmonary Embolism Acute; Pulmonary Embolism (Diagnosis)

Detailed Description

Pulmonary embolism (PE) is currently the third leading cause of cardiovascular mortality worldwide. According to international guidelines, patients who are hemodynamically unstable at presentation (classified as high-risk according to the current European Society of Cardiology classification) and those at intermediate-high risk-defined as patients who are hemodynamically stable at admission but present with right ventricular dysfunction and positive cardiac ischemia biomarkers and subsequently develop sudden hemodynamic deterioration, should undergo reperfusion as early as possible.

At present, reperfusion in these patients is mainly achieved through systemic thrombolysis or percutaneous treatments. However, these strategies are frequently underutilized because of patients' comorbidities and bleeding risk. Notably, current international guidelines do not define a specific time window within which reperfusion should be performed using either approach, in contrast to what is well established in guidelines for acute myocardial infarction and ischemic stroke.

Given that most in-hospital deaths related to PE occur within the first hours after symptom onset and hospital admission, and considering that the histological composition of thrombi undergoes time-dependent changes that may partially reduce the effectiveness of reperfusion therapies, identifying a temporal cutoff within which reperfusion confers maximal clinical benefit would be highly relevant. Such a cutoff could improve both patient survival and the prevention of hemodynamic deterioration when performing systemic or percutaneous reperfusion.

To address this knowledge gap, we propose a national, multicenter, prospective observational study that could also could serve as a platform for registry-based randomized clinical trials. The primary aim of the study is to identify optimal management strategies for patients with intermediate-high-risk or high-risk PE, with a particular focus on the most appropriate timing of systemic reperfusion or catheter-directed therapies (CDTs), when indicated, and to evaluate their prognostic impact. Specifically, the study will assess the relationship between reperfusion timing (systemic thrombolysis or CDTs) and in-hospital mortality. Additionally, the association between different reperfusion time windows and the occurrence of haemorrhagic or cardiovascular complications will be evaluated.

• Study Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

• Study Contact: Name: Claudio Bilato, MD PhD; Phone Number: +390444479106; Email: claudio.bilato@aulss8.veneto.it

Study Locations

• Italy
  • Milano
    • Milan, Milano, Italy, 20162
      • Recruiting
      • UO Unità di Cure Intensive Cardiologiche e Cardiologia 1, Ospedale Niguarda, Milano
      • Principal Investigator: Claudia Colombo, MD
      • Contact: Claudia Colombo, MD; Phone Number: +390264442565; Email: claudia.colombo@ospealeniguarda.it
      • Sub-Investigator: Alice Sacco, MD
      • Sub-Investigator: Fabrizio Oliva, MD
  • Padova
    • Monselice, Padova, Italy, 35043
      • Recruiting
      • UOC di Cardiologia, Ospedali Riuniti Padova Sud, Monselice, Italia
      • Contact: Marco Zuin, MD MS; Phone Number: +390429715631; Email: marco.zuin@aulss6.veneto.it
  • Pavia
    • Pavia, Pavia, Italy, 27100
      • Recruiting
      • IRCCS Policlinico San Matteo
      • Contact: Leonardo De Luca, MD PhD; Phone Number: +390382503158; Email: l.deluca@smatteo.pv.it
      • Principal Investigator: Leonardo De Luca, MD PhD
      • Sub-Investigator: Stefano Ghio, MD PhD
      • Sub-Investigator: Guido Tavazzi, MD PhD
  • Perugia
    • Perugia, Perugia, Italy, 06129
      • Recruiting
      • UO di Sezione di Medicina Interna e Cardiovascolare, Ospedale Santa Maria della Misericordia, Perugia, Italia
      • Contact: Cecilia Becattini, MD PhD; Phone Number: +390755786424; Email: cecilia.becattini@unipg.it
      • Sub-Investigator: Maria Cristina Vedovati, MD PhD
      • Principal Investigator: Cecilia Becattini, MD PhD
  • Pisa
    • Pisa, Pisa, Italy, 56126
      • Recruiting
      • UO di Cardiologia 1, Azienda Ospedaliero Universitaria Pisana, Pisa, Italia
      • Contact: Rosalinda Madonna, MD PhD; Phone Number: +39050996975; Email: rosalinda.madonna@unipi.it
      • Principal Investigator: Rosalinda Madonna, MD PhD
      • Sub-Investigator: Raffaele De Caterina, MD PhD
  • Torino
    • Torino, Torino, Italy, 10128
      • Recruiting
      • UO di Cardiologia, Azienda Ospedaliera Ordine Mauriziano di Torino
      • Principal Investigator: Giuseppe Musumeci, MD
      • Contact: Giuseppe Musumeci, MD; Phone Number: +390115082515; Email: giuseppe.musumeci@gmail.com
  • Vicenza
    • Arzignano, Vicenza, Italy, 36071
      • Recruiting
      • UOC di Cardiologia, Ospedali dell'Ovest Vicentino, Arzignano, IItalia
      • Contact: Claudio Bilato, MD PhD; Phone Number: +390444931163; Email: claudio.bilato@aulss8.veneto.it
      • Principal Investigator: Claudio Bilato, MD PhD
      • Sub-Investigator: Chiara Dalla Valle, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with a confirmed diagnosis of high-risk or intermediate-high-risk pulmonary embolism according to the 2019 European Society of Cardiology guidelines.

Description

Inclusion Criteria:

• Age ≥ 18 years
• Patients with a diagnosis of intermediate-high or high pulmonary embolism confirmed by computed tomography pulmonary angiography (CTPA), pulmonary angiography, or echocardiography (evidence of a floating thrombus in the right atrium or right ventricle, or proximal visualization of thrombus in the pulmonary artery).
• Classified as high-risk or intermediate-high-risk according to the 2019 European Society of Cardiology guidelines.
• Provision of informed consent for the processing of personal data.

Exclusion Criteria:

• Age < 18 years
• Patients in whom a diagnosis of acute high-risk or intermediate-high-risk pulmonary embolism has been excluded.
• Inability to provide informed consent.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Patients with intermediate-high or high-risk pulmonary embolism; Patients with intermediate-high or high-risk pulmonary embolism stratified according to the ESC 2019 guidelines

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	Correlation between time to reperfusion (measured in hours from hospital admission to initiation of systemic thrombolysis or catheter-directed therapies [CDTs]) and in-hospital mortality rate (rate of patients) among patients with intermediate-high- and high-risk acute pulmonary embolism.	From enrollment to the end of treatment at 30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complications	Association between different reperfusion time windows and techniques and the occurrence of haemorrhagic or cardiovascular complications among patients with intermediate-high and high-risk with acute pulmonary embolism	From enrollment to the end of treatment at 30 days

Collaborators and Investigators

• Sponsor: Azienda ULSS 8 Berica
• Investigators: Study Director: Marco Zuin, MD MS, Department of Translational Medicine, University of Ferrara, Italy; Principal Investigator: Claudio Bilato, MD PhD, Department of Cardiology, Azienda AULSS 8 Berica, Arzignano (Vicenza), Italy

Study record dates

Study Major Dates

• Study Start (Actual): November 25, 2025
• Primary Completion (Estimated): October 30, 2026
• Study Completion (Estimated): October 30, 2026

Study Registration Dates

• First Submitted: February 12, 2026
• First Submitted That Met QC Criteria: February 25, 2026
• First Posted (Actual): February 27, 2026

Study Record Updates

• Last Update Posted (Actual): March 3, 2026
• Last Update Submitted That Met QC Criteria: March 1, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Anticoagulation; Fibrinolysis; Catheter-directed treatments; Time of Reperfusion
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Embolism and Thrombosis; Embolism; Pathological Conditions, Signs and Symptoms; Pulmonary Embolism; Disease
• Other Study ID Numbers: OPTIRAPE - 775CET 2026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No