Reperfusion Treatment in Acute Pulmonary Embolism

Recruiting

• Conditions: Pulmonary Embolism
• Interventions: Drug: Alteplase; Procedure: Catheter directed intervention, any device

• Registration Number: NCT07003646
• Lead Sponsor: Sahlgrenska University Hospital

Brief Summary

International guidelines recommend immediate reperfusion with systemic thrombolysis (ST) as first-line treatment in high-risk pulmonary embolism (PE). The therapy improves hemodynamics and overall survival but is also associated with a significant risk of severe bleeding. Catheter-directed intervention (CDI) is recommended as an alternative reperfusion therapy in high-risk PE when ST is contraindicated or has failed, as well as in patients who deteriorate or fail to improve during anticoagulation (AC) treatment. Despite lack of high-quality evidence and randomized studies between CDI and standard care, the use of CDI is spreading rapidly in high-risk PE and in less severe PE not fulfilling current treatment criteria.

Detailed Description

Several CDI methods are available, including mechanical thrombectomy (MT) and catheter-directed thrombolysis (CDT), but no method is currently recommended over the other. In Sweden, the MT device FlowTriever® (FT) was introduced in 2021 and has since then been the predominant method. Industry sponsored trials have investigated FT in uncontrolled observational trials and primarily in intermediate-risk PE. The investigator-initiated research on FT is limited to relatively small, descriptive, single-arm studies, or trials focusing on intermediate-risk PE.

There are several ongoing trials comparing different CDI methods to anticoagulation. However, in clinical practice, patients with acute PE may be subjected to different reperfusion strategies depending on severity and available resources. The PE-NORDIC observational study will compare the outcomes of different patient groups treated with current CDI methods used in the Nordic countries to patients treated with ST.

Study Timeline

• Study Start: 2025-04-01
• Status Verified: 2025-05
• Study First Submitted: 2025-05-16
• Study First Submitted QC: 2025-05-26
• Last Update Submitted: 2025-05-26
• Study First Posted: 2025-06-04
• Last Update Posted: 2025-06-04
• Primary Completion: 2028-05-01
• Study Completion: 2029-05-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 220

Inclusion Criteria

• All adult patients (≥18 years), including pregnant women, with verified (CTPA, angiography or scintigraphy) acute pulmonary embolism who are planned for, or have received, treatment with catheter directed intervention or systemic thrombolysis
• Informed consent (for patients who do not survive before informed consent can be obtained, a waiver of consent applies)

Exclusion Criteria

• Ongoing enrolment in interventional catheter directed intervention trial
• Surgical embolectomy as primary reperfusion treatment

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Systemic thrombolysis	Alteplase	Intravenous thrombolysis with tissue-type plasminogen activator (tPA)
Catheter-directed intervention	Catheter directed intervention, any device	Catheter-directed intervention, any device

Primary Outcome Measures

Name	Time	Method
Composite of severe bleeding or mortality at 30 days	From treatment to day 30 after treatment	A composite of severe bleeding according to GUSTO (defined as intracranial bleeding or bleeding with substantial hemodynamic com-promise requiring treatment) or death within 30 days after treatment

Secondary Outcome Measures

Name	Time	Method
Change in RV/LV ratio	72 hours	Change in right ventricular to left ventricular (RV/LV) diameter ratio before and within 72 h after treatment.
RV dysfunction	1 year	Examined by echocardiogram in association with follow-up visit 1 and 2
Persisting dyspnea	1 year	Self-reported level of dyspnea at follow-up visit 1 compared to discharge date and at follow-up visit 2 to compared to visit 1.
6-minute walk test	1 year	Distance (meters) walked in a 6-minute walk test performed at follow-up visit 1 and 2
Sit-to-stand 60 test	1 year	Number of stand-ups performed in a sit-to-stand 60 test performed at follow-up visit 1 and 2
Recurrent PE	30 days	Clinically relevant recurrence of PE
Hospital free days	30 days	Hospital free days between treatment and 30 days
ICU/HDU free days	30 days	Intensive care unit (ICU) and/or high dependency unit (HDU) free days between treatment and 30 days
Mortality	30 days	Cause of death
Bleeding	30 days	Defined by GUSTO criteria, severe/non-severe.
Rescue treatment	30 days	Incidence of rescue treatment for PE (Systemic thrombolysis/Catheter-directed intervention/extracorporeal membrane oxygenation (ECMO)/surgical embolectomy)
PEmb-QoL	1 year	Pulmonary Embolism Quality of Life Questionnaire. Disease-specific health-related quality of life.; FC: Frequency of complaints (8 items, reverse scoring where lower scores correspond to better quality of life).; AD: Activities of daily living limitations (13 items, reverse scoring where lower scores correspond to better quality of life).; WR: Work-related problems (4 items, reverse scoring where lower scores correspond to better quality of life).; SL: Social limitations (1 item).; IC: Intensity of complaints (2 items).; EC: Emotional complaints (10 items, reverse scoring where lower scores correspond to better quality of life).
MRC dyspnoea scale	1 year	Medical research council dyspnoea scale. 0-4, a higher number corresponds to more dyspnoea.
EQ-5D-5L	1 year	EuroQol 5-dimension 5-level questionnaire. Generic health-related quality of life assessment.; Movement (1-5), 1 corresponds to high and 5 to low movement level (descriptive); Care (1-5), 1 corresponds to high and 5 to low care level (descriptive); Activity (1-5), 1 corresponds to high and 5 to low activity level (descriptive); Pain (1-5), 1 corresponds to low and 5 to high pain level (descriptive); Anxiety (1-5), 1 corresponds to low and 5 to high anxiety level (descriptive); EQ-VAS (0-100), where 0 corresponds to worst health and 100 to best possible
PVFS scale	1 year	Post venous thromboembolism functional status scale (0-4) 0 corresponds to not affected of thromboembolism daily, 4 severely affected in daily life.
Incidence of CTED/CTEPH	1 year	Incidence of chronic thromboembolic pulmonary vascular disease (CTED) or chronic thromboembolic pulmonary hypertension (CTEPH)
Cardiac biomarkers	1 year	Troponin and NTproBNP

Trial Locations

Locations (13)

Aarhus University Hospital; 🇩🇰 Aarhus, Denmark

Rigshospitalet; 🇩🇰 Copenhagen, Denmark

Odense University Hospital; 🇩🇰 Odense, Denmark

Sahlgrenska University Hospital; 🇸🇪 Gothenburg, Sweden

Linköping University Hospital; 🇸🇪 Linköping, Sweden

Sunderby Hospital; 🇸🇪 Luleå, Sweden

Skåne University Hospital; 🇸🇪 Lund, Sweden

Danderyd Hospital; 🇸🇪 Stockholm, Sweden

Karolinska University Hospital Huddinge; 🇸🇪 Stockholm, Sweden

Karolinska University Hospital Solna; 🇸🇪 Stockholm, Sweden

Södersjukhuset; 🇸🇪 Stockholm, Sweden

Uppsala University Hospital; 🇸🇪 Uppsala, Sweden

Örebro University Hospital; 🇸🇪 Örebro, Sweden