Ultrasound-facilitated, Catheter-directed, Thrombolysis in Intermediate-high Risk Pulmonary Embolism
- Conditions
- Pulmonary Embolism
- Interventions
- Device: EkoSonicTM Endovascular System
- Registration Number
- NCT04790370
- Lead Sponsor
- Boston Scientific Corporation
- Brief Summary
There are many available treatments for pulmonary embolism (PE), but the best treatment for this condition is not known. The HI-PEITHO study will compare two treatment options that are both available on the market for the treatment of PE.
Patients will be randomized 1:1 to receive either blood thinners (anticoagulation) or blood thinners (anticoagulation) in combination with a device called the EkoSonicTM Endovascular device to dissolve blood clots. Patients will be followed for 12 months after randomization and have assessments while in the hospital as well as at 7 days, 30 days, 6 months and 12 months after randomization. The study will try to find out if one of these treatments is better than the other at reducing the risk of death and other serious problems.
- Detailed Description
This study will assess whether ultrasound-facilitated, catheter-directed thrombolysis and standard anticoagulation are associated with a significant reduction in the composite outcome of pulmonary embolism (PE)-related mortality, cardiorespiratory decompensation or collapse, or nonfatal symptomatic and objectively confirmed recurrence of PE compared to anticoagulation alone within seven days of randomization
The HI-PEITHO study has been designed to address the important gaps in clinical evidence by comparing the clinical benefit of the ultrasound-facilitated local delivery of a low dose thrombolytic agent and anticoagulation with those of anticoagulation alone in patients with intermediate-high risk PE at a higher estimated risk of early decompensation based on clinical parameters at presentation.
This study has a focus on improving the safety of thrombolysis and advancing the concept of intermediate-high risk and the PE severity criteria, to better identify patients who may clinically benefit from thrombolysis.
The results of this study will contribute further evidence to the existing data on the treatment and outcomes of acute, intermediate-high risk PE and provide controlled data related to catheter-based interventions.
Data will be entered by the site into an electronic database. The database will include data checks to compare data entered into the database against predefined rules for ranges and consistency with other data fields in the database.
Site monitoring will take place with source data verification to assess the accuracy and completeness of registry data by comparing the data to medical records and study assessments.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 544
-
Age 18-80 years, inclusive
-
Objectively confirmed acute PE, based on computed tomography pulmonary angiography (CTPA) showing a filling defect in at least one main or proximal lobar pulmonary artery
-
Elevated risk of early death/hemodynamic collapse, indicated by at least two of the following new-onset clinical criteria:
- ECG-documented tachycardia with heart rate ≥100 beats per minute, not due to hypovolemia, arrhythmia, or sepsis;
- SBP ≤ 110 mm Hg for at least 15 minutes;
- respiratory rate > 20 x min-1 or oxygen saturation on pulse oximetry (SpO2) < 90% (or partial arterial oxygen pressure < 60 mmHg) at rest while breathing room air;
-
Right-to-left ventricular (RV/LV) diameter ratio ≥ 1.0 on CTPA
-
Serum troponin I or T levels above the upper limit of normal
-
Signed informed consent
-
Hemodynamic instability*, i.e. at least one of the following present:
- cardiac arrest or need for cardiopulmonary resuscitation;
- need for ECMO, or ECMO initiated before randomization
- PE-related shock, defined as: (i) SBP < 90 mmHg, or vasopressors required to achieve SBP ≥ 90 mmHg, despite an adequate volume status; and (ii) end-organ hypoperfusion (altered mental status; oliguria/anuria; increased serum lactate);
- isolated persistent hypotension (SBP < 90 mmHg, or a systolic pressure drop by at least 40 mmHg for at least 15 minutes), not caused by new-onset arrhythmia, hypovolemia, or sepsis * Patients who presented with temporary need for fluid resuscitation and/or low-dose catecholamines may be included, provided that they could be stabilized within 2 hours of admission and maintain SBP of ≥ 90 mmHg and adequate organ perfusion without catecholamine infusion.
-
Need for admission to an intensive care unit for a reason other than the index PE episode. NB: Patients who test positive for SARS-CoV-2 can be enrolled where the investigator believes that the pulmonary embolism is the dominant pathology in the patient's clinical presentation and qualifying cardiorespiratory parameters.
-
Temperature above 39 degrees C / 102.2 degrees F
-
Logistical reasons limiting the rapid availability of interventional procedures to treat acute PE (e.g., during the outbreak of an epidemic)
-
Index PE symptom duration > 14 days
-
Active bleeding
-
History of intracranial or intraocular bleeding at any time
-
Stroke or transient ischemic attack within the past 6 months, or previous stroke at any time if associated with permanent disability
-
Central nervous system neoplasm, or metastatic cancer
-
Major neurologic, ophthalmologic, abdominal, cardiac, thoracic, vascular or orthopedic surgery or trauma (including syncope-associated with head strike or skeletal fracture) within the past 3 weeks
-
Platelet count < 100 x 109 x L-1
-
Patients who have received a once-daily therapeutic dose of LMWH or a therapeutic dose of fondaparinux within 24 hours prior to randomization
-
Patients who have received one of the direct oral anticoagulants apixaban or rivaroxaban within 12 hours prior to randomization
-
Patients who have received one of the direct oral anticoagulants dabigatran or edoxaban for the index PE episode, as these drugs are not approved for patients who have not received heparin for at least 5 days
-
Administration of a thrombolytic agent or a glycoprotein IIb/IIIa receptor antagonist during the current hospital stay and/or within 30 days, for any reason
-
Chronic treatment with antiplatelet agents other than low-dose acetylsalicylic acid or clopidogrel 75 mg once daily (but not both). Dual antiplatelet therapy is excluded.
-
Chronic treatment with a direct oral anticoagulant (apixaban, dabigatran, edoxaban or rivaroxaban)
-
Chronic treatment with a vitamin K antagonist, or known coagulopathy including severe hepatic dysfunction, with an International Normalized Ratio (INR) > 1.5
-
Pregnancy or lactation
-
Previous inclusion in the study
-
Known hypersensitivity to alteplase, LMWH or UFH, or to any of the excipients
-
Life expectancy less than 6 months
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Anticoagulation and EkoSonicTM Endovascular System Anticoagulation with heparin Low-molecular weight heparin (LMWH) or unfractionated heparin (UFH) and EkoSonicTM Endovascular System \[ultrasound-facilitated catheter-directed delivery of thrombolytic: 2 mg bolus/catheter + 1 mg/hour/catheter for 7 hours (total of 9 or 18 mg\] Anticoagulation Anticoagulation with heparin Low-molecular weight heparin (LMWH) or unfractionated heparin (UFH) Anticoagulation and EkoSonicTM Endovascular System EkoSonicTM Endovascular System Low-molecular weight heparin (LMWH) or unfractionated heparin (UFH) and EkoSonicTM Endovascular System \[ultrasound-facilitated catheter-directed delivery of thrombolytic: 2 mg bolus/catheter + 1 mg/hour/catheter for 7 hours (total of 9 or 18 mg\]
- Primary Outcome Measures
Name Time Method PE-related mortality Within seven days of randomization death resulting from PE
PE recurrence Within seven days of randomization nonfatal symptomatic and objectively confirmed recurrence of PE
Cardiorespiratory decompensation or collapse Within seven days of randomization Cardiorespiratory collapse or decompensation is defined as at least one of the following criteria:
1. cardiac arrest or need for CPR at any time between randomization and day 7;
2. signs of shock: new-onset persistent arterial hypotension (systolic blood pressure (SBP) below 90 mmHg or SBP drop by at least 40 mm Hg, over at least 15 minutes and despite an adequate volume status; or need for vasopressors to maintain SBP of at least 90 mmHg), accompanied by end-organ hypoperfusion (altered mental status; oliguria/anuria; or increased serum lactate) at any time between randomization and day 7;
3. placement on extracorporeal membrane oxygenation (ECMO) at any time between randomization and day 7;
4. intubation, or initiation of noninvasive mechanical ventilation at any time between randomization and day 7;
5. National Early Warning Score (NEWS) of 9 or higher, between 24 hours and 7 days after randomization, confirmed on consecutive measurements taken twice, 15 minutes apart.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (72)
GFO Kliniken Bonn
🇩🇪Bonn, Germany
Klinikum Chemnitz
🇩🇪Chemnitz, Germany
Klinikum Bielefeld
🇩🇪Bielefeld, Germany
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Cedars - Sinai Medical Center
🇺🇸Los Angeles, California, United States
Christiana Hospital
🇺🇸Newark, Delaware, United States
Washington Hospital Center
🇺🇸Washington, District of Columbia, United States
Piedmont Hospital
🇺🇸Atlanta, Georgia, United States
Emory University Hospital
🇺🇸Atlanta, Georgia, United States
Augusta University
🇺🇸Augusta, Georgia, United States
Advocate Good Samaritan Hospital
🇺🇸Downers Grove, Illinois, United States
St. Vincent Heart Center of Indiana
🇺🇸Indianapolis, Indiana, United States
Methodist Hospitals
🇺🇸Merrillville, Indiana, United States
Jewish Hospital
🇺🇸Louisville, Kentucky, United States
Baptist Health East Louisville
🇺🇸Lousville, Kentucky, United States
University of Maryland School of Medicine
🇺🇸Baltimore, Maryland, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
University of Michigan Hospitals
🇺🇸Ann Arbor, Michigan, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
St. John Hospital & Medical Center
🇺🇸Detroit, Michigan, United States
Mayo Clinic Foundation
🇺🇸Rochester, Minnesota, United States
North Mississippi Medical Center
🇺🇸Tupelo, Mississippi, United States
Nebraska Methodist Hospital
🇺🇸Omaha, Nebraska, United States
Dartmouth-Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Cooper Hospital - University Medical Center
🇺🇸Camden, New Jersey, United States
Newark Beth Israel Medical Center
🇺🇸Newark, New Jersey, United States
Mount Sinai Medical Center
🇺🇸New York, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Lenox Hill Hospital
🇺🇸New York, New York, United States
St. Francis Hospital
🇺🇸Roslyn, New York, United States
University Hospitals of Cleveland
🇺🇸Cleveland, Ohio, United States
Kettering Health
🇺🇸Kettering, Ohio, United States
University of Oklahoma Health Science Center
🇺🇸Oklahoma City, Oklahoma, United States
Wellmont Holston Valley Medical Center
🇺🇸Kingsport, Tennessee, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Seton Medical Center
🇺🇸Austin, Texas, United States
Houston Methodist Sugarland Hospital
🇺🇸Houston, Texas, United States
The Heart Hospital Baylor Plano
🇺🇸Plano, Texas, United States
University of Virginia Medical Center
🇺🇸Charlottesville, Virginia, United States
University of Wisconsin Hospitals
🇺🇸Madison, Wisconsin, United States
A.o. LKH Univ.-Kliniken Innsbruck
🇦🇹Innsbruck, Austria
Universitätsklinikum St. Pölten
🇦🇹St. Pölten, Austria
Austria Klinik Ottakring Vienna
🇦🇹Vienna, Austria
Allgemeines Krankenhaus AKH
🇦🇹Wien, Austria
CHU de Besancon
🇫🇷Besançon, France
Hopital Nord de Marseille
🇫🇷Marseille, France
CHU (Nimes Cedex)
🇫🇷Nîmes, France
Hôpital Européen Georges Pompidou (HEGP)
🇫🇷Paris, France
Uniklinik Aachen
🇩🇪Aachen, Germany
Klinikum Coburg GmbH
🇩🇪Coburg, Germany
Universitaetsklinikum Freiburg
🇩🇪Freiburg, Germany
Klinik Immenstadt
🇩🇪Immenstädt, Germany
Universitaetsklinikum Schleswig-Holstein
🇩🇪Lübeck, Germany
Johannes Gutenberg Universitaet Mainz
🇩🇪Mainz, Germany
Klinikum Rechts der Isar
🇩🇪Munich, Germany
Universitaetsklinikum Tuebingen
🇩🇪Tuebingen, Germany
Universitaetsklinikum Wuerzburg
🇩🇪Würzburg, Germany
Mater Misericordiae University Hospital
🇮🇪Dublin, Ireland
University Hospital Galway
🇮🇪Galway, Ireland
Leiden University Medical Center
🇳🇱Leiden, Netherlands
St. Antonius Ziekenhuis
🇳🇱Nieuwegein, Netherlands
Universitair Medisch Centrum
🇳🇱Utrecht, Netherlands
John Paul II Hospital
🇵🇱Kraków, Poland
Uniwersytecki Szpital Kliniczny w Poznaniu
🇵🇱Poznań, Poland
Medical University of Warsaw
🇵🇱Warsaw, Poland
University Hospital Basel
🇨🇭Basel, Switzerland
Centre Hospitalier Universitaire Vaudois
🇨🇭Lausanne, Switzerland
University Hospital Zurich
🇨🇭Zürich, Switzerland
University Hospital of Wales
🇬🇧Cardiff, United Kingdom
Guys and St. Thomas NHS Foundation Trust
🇬🇧London, United Kingdom
The Royal Free Hospital
🇬🇧London, United Kingdom
Northwick Park Hospital
🇬🇧Middlesex, United Kingdom