Ultrasound-facilitated, Catheter-directed, Thrombolysis in Intermediate-high Risk Pulmonary Embolism

NCT04790370 | Active Not Recruiting Phase 4 DMC FDA Device

• 1 other identifier: S2479
• Study Type: interventional
• Target: 544
• Locations: 9 countries
• Sites: 60

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.

Conditions

Pulmonary Embolism

Keywords

Acute intermediate-high risk pulmonary embolism; Ultrasound-facilitated, catheter-directed thrombolysis; Thrombolysis

Outcome Measures

Primary Outcomes (3)

• PE-related mortality

  death resulting from PE

  Within seven days of randomization

• PE recurrence

  nonfatal symptomatic and objectively confirmed recurrence of PE

  Within seven days of randomization

• Cardiorespiratory decompensation or collapse

  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.

  Within seven days of randomization

Other Outcomes (21)

• Change in the RV-to-LV diameter ratio as measured by echocardiography

  Between baseline and 48±6 hours

• PE-related death

  Within 7 days

• Cardiorespiratory decompensation

  Within 7 days

Study Arms (2)

Anticoagulation

ACTIVE COMPARATOR

Low-molecular weight heparin (LMWH) or unfractionated heparin (UFH)

Drug: Anticoagulation with heparin

Anticoagulation and EkoSonicTM Endovascular System

ACTIVE COMPARATOR

Low-molecular weight heparin (LMWH) or unfractionated heparin (UFH) and EkoSonicTM Endovascular System \[ultrasound-facilitated catheter-directed delivery of thrombolytic: 2 mg bolus/catheter + 1 mg/hour/catheter for 7 hours (total of 9 or 18 mg\]

Drug: Anticoagulation with heparin; Device: EkoSonicTM Endovascular System

Interventions

EkoSonicTM Endovascular System DEVICE

EkoSonicTM Endovascular System \[ultrasound-facilitated catheter-directed delivery of thrombolytic: 2 mg bolus/catheter + 1 mg/hour/catheter for 7 hours (total of 9 or 18 mg\]

Also known as: EKOS, USCDT, CDT, thrombolysis, fibrinolysis

Anticoagulation and EkoSonicTM Endovascular System

Anticoagulation with heparin DRUG

Low-molecular weight heparin (LMWH) or unfractionated heparin (UFH)

Also known as: heparin, LMWH, UFH, anticoag, antiplatelet

Anticoagulation; Anticoagulation and EkoSonicTM Endovascular System

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 10\^9 x L\^-1

Sponsors & Collaborators

• Boston Scientific Corporation: lead
• National PERT Consortium, Inc.: collaborator
• University Medical Center Mainz: collaborator

Study Sites (60)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Cedars - Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Christiana Hospital

Newark, Delaware, 19718, United States

Location

Piedmont Hospital

Atlanta, Georgia, 30309, United States

Location

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

Augusta University

Augusta, Georgia, 30904, United States

Location

Methodist Hospitals

Merrillville, Indiana, 46410, United States

Location

Baptist Health East Louisville

Lousville, Kentucky, 40207, United States

Location

University of Maryland School of Medicine

Baltimore, Maryland, 21201, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Michigan Hospitals

Ann Arbor, Michigan, 48109, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

North Mississippi Medical Center

Tupelo, Mississippi, 38801, United States

Location

Nebraska Methodist Hospital

Omaha, Nebraska, 68114, United States

Location

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Newark Beth Israel Medical Center

Newark, New Jersey, 07112, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Lenox Hill Hospital

New York, New York, 10075, United States

Location

University Hospitals of Cleveland

Cleveland, Ohio, 44106, United States

Location

Kettering Health

Kettering, Ohio, 45429, United States

Location

Wellmont Holston Valley Medical Center

Kingsport, Tennessee, 37660, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Seton Medical Center

Austin, Texas, 78705, United States

Location

Houston Methodist Sugarland Hospital

Houston, Texas, 77479, United States

Location

The Heart Hospital Baylor Plano

Plano, Texas, 75093, United States

Location

University of Virginia Medical Center

Charlottesville, Virginia, 22908, United States

Location

University of Wisconsin Hospitals

Madison, Wisconsin, 53792, United States

Location

A.o. LKH Univ.-Kliniken Innsbruck

Innsbruck, Austria

Location

Universitätsklinikum St. Pölten

Sankt Pölten, Austria

Location

Allgemeines Krankenhaus AKH

Vienna, Austria

Location

Austria Klinik Ottakring Vienna

Vienna, Austria

Location

CHU de Besancon

Besançon, France

Location

CHU (Nimes Cedex)

Nîmes, France

Location

Hôpital Européen Georges Pompidou (HEGP)

Paris, France

Location

Uniklinik Aachen

Aachen, Germany

Location

Klinikum Bielefeld

Bielefeld, Germany

Location

GFO Kliniken Bonn

Bonn, Germany

Location

Klinikum Chemnitz

Chemnitz, Germany

Location

Universitaetsklinikum Freiburg

Freiburg im Breisgau, Germany

Location

Klinik Immenstadt

Immenstädt, Germany

Location

Universitaetsklinikum Schleswig-Holstein

Lübeck, Germany

Location

Johannes Gutenberg Universitaet Mainz

Mainz, Germany

Location

Klinikum Rechts der Isar

Munich, Germany

Location

Universitaetsklinikum Tuebingen

Tübingen, Germany

Location

Universitaetsklinikum Wuerzburg

Würzburg, Germany

Location

Mater Misericordiae University Hospital

Dublin, Ireland

Location

University Hospital Galway

Galway, Ireland

Location

Leiden University Medical Center

Leiden, Netherlands

Location

St. Antonius Ziekenhuis

Nieuwegein, Netherlands

Location

Universitair Medisch Centrum

Utrecht, Netherlands

Location

John Paul II Hospital

Krakow, Poland

Location

Uniwersytecki Szpital Kliniczny w Poznaniu

Poznan, Poland

Location

Medical University of Warsaw

Warsaw, Poland

Location

University Hospital Basel

Basel, Switzerland

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, Switzerland

Location

University Hospital Zurich

Zurich, Switzerland

Location

University Hospital of Wales

Cardiff, United Kingdom

Location

The Royal Free Hospital

London, United Kingdom

Location

Northwick Park Hospital

Middlesex, United Kingdom

Location

Related Publications (29)

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MeSH Terms

Conditions

Pulmonary Embolism

Interventions

Heparin; Heparin, Low-Molecular-Weight

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Embolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Officials

• Stavros Konstantinides, MD

  University Medical Center Mainz, Mainz, Germany

  PRINCIPAL INVESTIGATOR

• Kenneth Rosenfield, MD

  Massachusetts General Hospital, Boston, Massachusetts, USA

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Blinded adjudication of primary composite outcome
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 1:1 randomization

Study Record Dates

• First Submitted: March 2, 2021
• First Posted: March 10, 2021
• Study Start: August 2, 2021
• Primary Completion: July 31, 2025
• Study Completion (Estimated): August 1, 2026
• Last Updated: June 4, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

IE (2); PL (3); FR (3); US (28); AU (4); NL (3); CH (3); GB (3); DE (11)