Optimum Duration of Acoustic Pulse Thrombolysis Procedure in Acute Pulmonary Embolism

NCT02396758 | Completed Phase 4 Results

• 2 other identifiers: EKOS-122016-000502-11
• Study Type: interventional
• Target: 131
• Locations: 2 countries
• Sites: 21

Brief Summary

The objective is to determine the optimum dose of thrombolytic and duration of the ultrasound procedure (together defined as the APT Procedure) as a treatment for acute submassive pulmonary embolism (PE). Symptomatic submassive PE are participants with acute (less than or equal to \[≤\]14 days) PE with normal systemic arterial blood pressure (greater than \[\>\] 90 mmHg) and evidence of RV dysfunction (right ventricular to left ventricular diameter ratio, that is; RV/LV ratio greater than or equal to \[≥\] 0.9). Participants with submassive PE will be randomized to one of four APT treatment groups: ultrasound of 2 and 6 hours (hrs) with r-tPA 2 milligrams (mg)/hr/catheter and ultrasound 4 and 6 hours with r-tPA, 1 mg/hr/catheter. On 08 June 2016, randomization into treatment group 4 (APT/6 hours-r-tPA/2 mg/hr/catheter) was closed following a reported intracranial hemorrhage (ICH) and death in a study participant in this arm.

Conditions

Pulmonary Embolism and Thrombosis

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in the Right Ventricle (RV) Diameter-to-Left Ventricle (LV) Diameter Ratio to 48 ± 6 Hours After the Start of the APT Procedure

  Change from baseline in RV/LV will be determined by computed tomographic angiography (CTA).

  Change from Baseline to 48 hrs ± 6 hours

• Number of Participants With Major Bleeding Within 72 Hours After Initiating the APT Procedure

  Criteria for major bleeding events, as defined by the International Society on Thrombosis and Haemostasis (ISTH): 1. Fatal bleeding and/or; 2. Symptomatic bleeding in a critical area or organ (intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome) and/or; 3. Bleeding causing a fall in hemoglobin level of 20 grams/liter (g/L) or more, or leading to transfusion of two or more units of whole blood or red blood cells.

  Day 3 (within 72 hours after initiating the APT procedure)

Secondary Outcomes (25)

• Percentage of Participants With Treatment Success of an APT Procedure

  From Baseline up to Day 30

• Change From Baseline in RV/LV at Days 0, 2, 30, 90, and 365, as Assessed by Echocardiograph.

  Baseline (Day -2 [within -48 hrs of APT start]), Day 0 (within 4 hours after APT end), Day 2 (48 [± 6] hrs of APT start), Day 30 (± 5 days), Day 90 (± 10 days) and Day 365 (± 14 days)

• Change From Baseline in Tricuspid Annular Plane Systolic Excursion (TAPSE) at Days 0, 2, 30, 90, and 365, as Assessed by Echocardiograph

  Baseline (Day -2 [within -48 hrs of APT start]), Day 0 (within 4 hours after APT end), Day 2 (48 [± 6] hrs of APT start), Day 30 (± 5 days), Day 90 (± 10 days) and Day 365 (± 14 days)

• Change From Baseline in Estimated Right Ventricular Systolic Pressure (RVSP) at Days 0, 2, 30, 90, and 365, as Assessed by Echocardiograph

  Baseline (Day -2 [within -48 hrs of APT start]), Day 0 (within 4 hours after APT end), Day 2 (48 [± 6] hrs of APT start), Day 30 (± 5 days), Day 90 (± 10 days) and Day 365 (± 14 days)

• Percentage of Participants With Collapse of the Inferior Vena Cava (IVC) With Respiration at Days 0, 2, 30, 90, and 365, as Assessed by Echocardiograph

  Baseline (Day -2 [within -48 hrs of APT start]), Day 0 (within 4 hours after APT end), Day 2 (48 [± 6] hrs of APT start), Day 30 (± 5 days), Day 90 (± 10 days) and Day 365 (± 14 days)

Study Arms (4)

APT/2 Hours-r-tPA/2 mg/hr/Catheter

EXPERIMENTAL

A total of 4 or 8 mg r-tPA (as 2 mg/hour \[hr\]/catheter) will be delivered through Ekosonic® Endovascular Device (EKOS) ultrasonic infusion catheter for 2 hrs.

Device: Ekosonic® Endovascular Device ultrasonic infusion catheter; Biological: Recombinant tissue plasminogen activator

APT/4 Hours-r-tPA/1 mg/hr/Catheter

EXPERIMENTAL

A total of 4 or 8 mg r-tPA (as 1 mg/hr/catheter) will be delivered through EKOS ultrasonic infusion catheter for 4 hrs.

Device: Ekosonic® Endovascular Device ultrasonic infusion catheter; Biological: Recombinant tissue plasminogen activator

APT/6 Hours-r-tPA/1 mg/hr/Catheter

EXPERIMENTAL

A total of 6 or 12 mg r-tPA (as 1 mg/hr/catheter) will be delivered through EKOS ultrasonic infusion catheter for 6 hrs.

Device: Ekosonic® Endovascular Device ultrasonic infusion catheter; Biological: Recombinant tissue plasminogen activator

APT/6 Hours-r-tPA/2 mg/hr/Catheter

EXPERIMENTAL

A total of 12 or 24 mg r-tPA (as 2 mg/hr/catheter) will be delivered through EKOS ultrasonic infusion catheter for 6 hrs.

Device: Ekosonic® Endovascular Device ultrasonic infusion catheter; Biological: Recombinant tissue plasminogen activator

Interventions

Ekosonic® Endovascular Device ultrasonic infusion catheter DEVICE

r-tPA will be administered via EKOS.

Also known as: Acoustic Pulse Thrombolysis Procedure (APT Procedure), EKOS

APT/2 Hours-r-tPA/2 mg/hr/Catheter; APT/4 Hours-r-tPA/1 mg/hr/Catheter; APT/6 Hours-r-tPA/1 mg/hr/Catheter; APT/6 Hours-r-tPA/2 mg/hr/Catheter

Recombinant tissue plasminogen activator BIOLOGICAL

Recombinant tissue plasminogen activator will be administered as per the dose and schedule specified in the arm.

Also known as: r-tPA

APT/2 Hours-r-tPA/2 mg/hr/Catheter; APT/4 Hours-r-tPA/1 mg/hr/Catheter; APT/6 Hours-r-tPA/1 mg/hr/Catheter; APT/6 Hours-r-tPA/2 mg/hr/Catheter

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female greater than or equal to (≥) 18 years of age and less than or equal to (≤) 75 years of age.
• CTA evidence of proximal PE (filling defect in at least one main or lobar pulmonary artery).
• PE symptom duration ≤14 days.
• Submassive PE: RV/LV diameter ≥ 0.9 from CTA and hemodynamically stable. For Participants in UK Sites: Submassive PE: RV/LV diameter ≥ 0.9 from CTA, hemodynamically stable and an elevated biomarker.
• Must be treated within 48 hours of diagnosis of PE by CTA.
• Signed Informed consent obtained from subject or Legally Authorized Representative.

You may not qualify if:

• Stroke or transient ischemic attack (TIA), head trauma, or other active intracranial or intraspinal disease within one year.
• Recent (within one month) or active bleeding from a major organ.
• Major surgery within seven days of screening for study enrollment.
• Clinician deems the subject high-risk for catastrophic bleeding.
• History of heparin-induced thrombocytopenia (HIT).
• Catheter-based pharmacomechanical treatment for PE within 3 days of study enrollment.
• Systolic blood pressure (SBP) less than 90 mm Hg and/or use of vasopressors.
• Cardiac arrest (including pulseless electrical activity and asystole) requiring active cardiopulmonary resuscitation (CPR).
• Evidence of irreversible neurological compromise.
• Life expectancy \< one year. For Participants in UK Sites: Life expectancy \< one year or enrollment in hospice care.
• Out-of-Range Laboratory Values: Hematocrit \< 30%, Platelets \< 100 thousand/microliter (μL), International normalized ratio (INR) \> 3.
• Creatinine outside the normal range for the treating institution.
• Participant is pregnant (positive pregnancy test; women of childbearing capacity must be tested) or breast feeding.
• Active cancer (metastatic, progressive, or treated within the last 6 months). Exception: participants with non-melanoma primary skin cancers are eligible to participate in the study.
• Known allergy, hypersensitivity, or thrombocytopenia from heparin, r-tPA, or iodinated contrast except for mild-moderate contrast allergies for which steroid pre-medication can be used.

Sponsors & Collaborators

• Boston Scientific Corporation: lead
• EKOS Corporation: collaborator

Study Sites (21)

Cedars Sinai

Beverly Hills, California, 90211, United States

Location

Tallahassee Memorial Hospital

Tallahassee, Florida, 32308, United States

Location

Florida Hospital Tampa

Tampa, Florida, 33613, United States

Location

Piedmont Hospital

Atlanta, Georgia, 30309, United States

Location

University Hospital

Augusta, Georgia, 30901, United States

Location

St. Vincent Medical Group

Indianapolis, Indiana, 46260, United States

Location

Jewish Hospital

Louisville, Kentucky, 40202, United States

Location

East Jefferson General Hospital

Metairie, Louisiana, 70006, United States

Location

Detroit Medical Center

Detroit, Michigan, 48201, United States

Location

Mount Carmel Health System

Columbus, Ohio, 43213, United States

Location

UPMC Hamot

Erie, Pennsylvania, 16507, United States

Location

Lankenau Medical Center

Wynnewood, Pennsylvania, 19096, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Houston Methodist Sugarland Hospital

Richmond, Texas, 77469, United States

Location

Inova Alexandria Hospital

Alexandria, Virginia, United States

Location

Providence Sacred Heart Medical Center

Spokane, Washington, 99204, United States

Location

Royal Devon & Exeter Hospital

Exeter, England, EX2 5DW, United Kingdom

Location

Medway Maritime Hospital

Gillingham, England, ME7 5NY, United Kingdom

Location

Royal Free Hospital

London, England, NW3 2QG, United Kingdom

Location

St. Thomas Hospital

London, England, SE1 7EH, United Kingdom

Location

Ninewells Hospital

Dundee, Scotland, DD1 9SY, United Kingdom

Location

Related Publications (2)

• Piazza G, Sterling KM, Tapson VF, Ouriel K, Sharp ASP, Liu PY, Goldhaber SZ. One-Year Echocardiographic, Functional, and Quality of Life Outcomes After Ultrasound-Facilitated Catheter-Based Fibrinolysis for Pulmonary Embolism. Circ Cardiovasc Interv. 2020 Aug;13(8):e009012. doi: 10.1161/CIRCINTERVENTIONS.120.009012. Epub 2020 Aug 6.

  PMID: 32757658 BACKGROUND

• Tapson VF, Sterling K, Jones N, Elder M, Tripathy U, Brower J, Maholic RL, Ross CB, Natarajan K, Fong P, Greenspon L, Tamaddon H, Piracha AR, Engelhardt T, Katopodis J, Marques V, Sharp ASP, Piazza G, Goldhaber SZ. A Randomized Trial of the Optimum Duration of Acoustic Pulse Thrombolysis Procedure in Acute Intermediate-Risk Pulmonary Embolism: The OPTALYSE PE Trial. JACC Cardiovasc Interv. 2018 Jul 23;11(14):1401-1410. doi: 10.1016/j.jcin.2018.04.008.

  PMID: 30025734 RESULT

MeSH Terms

Conditions

Pulmonary Embolism; Thrombosis

Interventions

Tissue Plasminogen Activator

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Biological Factors

Results Point of Contact

• Title: Nancy O'Connell
• Organization: Boston Scientific

nancy.oconnell@bsci.com

763-494-2706

Study Officials

• Victor Tapson, MD

  Cedar Sinai, Los Angeles

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2015
• First Posted: March 24, 2015
• Study Start: June 12, 2015
• Primary Completion: April 30, 2019
• Study Completion: January 30, 2020
• Last Updated: July 19, 2021
• Results First Posted: March 2, 2021

Record last verified: 2021-07

Locations

US (16); GB (5)