Submassive and Massive Pulmonary Embolism Treatment With Ultrasound Accelerated Thrombolysis Therapy

NCT01513759 | Completed Phase 3 Results

• 1 other identifier: EKOS 09
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 22

Brief Summary

The purpose of this study is to determine if the EKOS EkoSonic® Endovascular Device when used in conjunction with recombinant tissue plasminogen activator (t-PA) as a treatment for acute PE will decrease the ratio of right ventricle (RV) to left ventricle (LV) diameter within 48 =/- 6 hours in participants with massive or submassive PE.

Conditions

Pulmonary Embolism; Acute Pulmonary Embolism; Sub-massive Pulmonary Embolism; Massive Pulmonary Embolism; Pulmonary Thromboembolism

Keywords

Fibrinolysis; catheter directed fibrinolysis; ultrasound accelerated fibrinolysis; recombinant t-PA; Activase

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in the Right Ventricle (RV) Diameter-to-Left Ventricle (LV) Diameter Ratio Within 48 +/- 6 Hours of Initiation of Therapy

  Change from baseline in RV diameter/LV diameter ratio was determined by contrast-enhanced chest computed tomography (CT) within 48 +/- 6 hours after initiating ultrasound-accelerated catheter-directed fibrinolysis.

  Baseline, within 48 +/- 6 hours of initiation of therapy

• Number of Participants With Major Bleeding

  Bleeding adverse events were graded (severe or life-threatening, moderate or mild bleeding) according to the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) classification. The participant incidence of major bleeding events was defined as GUSTO moderate and severe events occurring within 72 hours after starting the ultrasound-accelerated catheter-directed fibrinolysis procedure. Mild: Does not meet criteria for moderate or severe; Moderate: Requires transfusion - No hemodynamic compromise; and Severe: Bleeding causes hemodynamic compromise and required intervention or intracranial hemorrhage. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

  From start of study drug infusion up to 72 hours

Secondary Outcomes (4)

• Change From Baseline in Pulmonary Artery Systolic Pressure at 48 Hours After Start of Therapy

  Baseline, Hour 48 after initiation of therapy

• Percentage of Participants With Symptomatic Recurrent Pulmonary Embolism (PE)

  Baseline up to Day 30

• Number of Participants Who Died Due to Any Cause

  Baseline up to Day 30

• Number of Devices That Could Not be Successfully Used for Infusion

  Baseline up to Day 30

Study Arms (1)

EkoSonic® Endovascular System

EXPERIMENTAL

Participants will receive a total of 24 milligrams (mg) of recombinant t-PA infusion, at an infusion rate of 1 milligrams/hour (mg/hr) per device (2 mg/hour for bilateral PE) delivered through the EkoSonic® Endovascular System. This regimen allows for a recombinant t-PA infusion time of 24 hours for one catheter and 12 hours for two catheters, respectively.

Drug: recombinant tissue plasminogen activator; Device: EKOS EkoSonic Endovascular System

Interventions

recombinant tissue plasminogen activator DRUG

Participants will receive 24 mg of r-tPA delivered via the EkoSonic Endovascular Device.

Also known as: r-tPA, t-PA, Alteplase

EkoSonic® Endovascular System

EKOS EkoSonic Endovascular System DEVICE

24 mg of r-tPA will be delivered through the EkoSonic Endovascular System.

Also known as: EkoSonic Endovascular Device, EkoSonic

EkoSonic® Endovascular System

Eligibility Criteria

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

You may qualify if:

• Computed tomography (CT) evidence of proximal PE (filling defect in at least one main or segmental pulmonary artery)
• PE symptom duration less than or equal to (\<=)14 days
• Informed consent can be obtained from participant or Legally Authorized Representative (LAR)
• Massive PE (syncope, systemic arterial hypotension, cardiogenic shock, or resuscitated cardiac arrest) or
• Submassive PE (RV diameter-to-LV diameter greater than or equal to \[\>=\] 0.9 on contrast-enhanced chest CT)

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
• Hematocrit less than (\<) 30 percent (%)
• Platelets \< 100 thousand/microliter (mcL)
• International Normalized Ratio (INR) greater than (\>) 3
• Activated partial thromboplastin time (aPTT) \>50 seconds on no anticoagulants
• Major surgery within seven days of screening for study enrollment
• Serum creatinine \>2 milligrams/deciliter (mg/dL)
• Clinician deems high-risk for catastrophic bleeding
• History of heparin-induced thrombocytopenia (HIT)
• Pregnancy
• Catheter-based pharmacomechanical treatment for pulmonary embolism within 3 days of study enrollment
• Systolic blood pressure less than 80 mm Hg despite vasopressor or inotropic support
• Cardiac arrest (including pulseless electrical activity and asystole) requiring active cardiopulmonary resuscitation (CPR)
• Evidence of irreversible neurological compromise

Sponsors & Collaborators

• Boston Scientific Corporation: lead
• EKOS Corporation: collaborator

Study Sites (22)

Baptist Health

Montgomery, Alabama, 36116, United States

Location

Memorial Medical Center

Modesto, California, 95355, United States

Location

Stanford University Medical Center

Stanford, California, 94305, United States

Location

Hartford Hospital

Hartford, Connecticut, United States

Location

Christiana Hospital

Newark, Delaware, 19718, United States

Location

Lakeland Regional Medical Center

Lakeland, Florida, 33805, United States

Location

Holmes Regional Medical Center

Melbourne, Florida, 32901, United States

Location

Florida Hospital

Orlando, Florida, 32803, United States

Location

Orlando Regional Medical Center

Orlando, Florida, 32806, United States

Location

Medical Center of Central Georgia

Macon, Georgia, 31201, United States

Location

Prairie Heart Institute

Springfield, Illinois, 62701, United States

Location

St. Vincent Hospital

Indianapolis, Indiana, United States

Location

University of Kentucky, Gill Heart Institute

Lexington, Kentucky, 40536, United States

Location

East Jefferson General Hospital

New Orleans, Louisiana, 70006, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Overlook Medical Center

Morristown, New Jersey, 07960, United States

Location

Holy Name Hospital

Teaneck, New Jersey, 07666, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Mt. Carmel East

Columbus, Ohio, 43213, United States

Location

The Miriam Hospital

Providence, Rhode Island, 02906, United States

Location

Providence Memorial and Sierra Medical Center

El Paso, Texas, 79902, United States

Location

Inova Alexandria Hospital

Alexandria, Virginia, 22304, United States

Location

Related Publications (2)

• Sadiq I, Goldhaber SZ, Liu PY, Piazza G; Submassive and Massive Pulmonary Embolism Treatment with Ultrasound AcceleraTed ThromboLysis ThErapy (SEATTLE II) Investigators. Risk factors for major bleeding in the SEATTLE II trial. Vasc Med. 2017 Feb;22(1):44-50. doi: 10.1177/1358863X16676355. Epub 2017 Jan 31.

  PMID: 27913777 DERIVED

• Piazza G, Hohlfelder B, Jaff MR, Ouriel K, Engelhardt TC, Sterling KM, Jones NJ, Gurley JC, Bhatheja R, Kennedy RJ, Goswami N, Natarajan K, Rundback J, Sadiq IR, Liu SK, Bhalla N, Raja ML, Weinstock BS, Cynamon J, Elmasri FF, Garcia MJ, Kumar M, Ayerdi J, Soukas P, Kuo W, Liu PY, Goldhaber SZ; SEATTLE II Investigators. A Prospective, Single-Arm, Multicenter Trial of Ultrasound-Facilitated, Catheter-Directed, Low-Dose Fibrinolysis for Acute Massive and Submassive Pulmonary Embolism: The SEATTLE II Study. JACC Cardiovasc Interv. 2015 Aug 24;8(10):1382-1392. doi: 10.1016/j.jcin.2015.04.020.

  PMID: 26315743 DERIVED

MeSH Terms

Conditions

Pulmonary Embolism

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: David Hahn
• Organization: EKOS Corporation

David.Hahn@btgplc.com

4254153100

Study Officials

• Narinder Bhalla, MD

  Baptist Health

  PRINCIPAL INVESTIGATOR

• William Kuo, MD

  Stanford Hospital and Clinics

  PRINCIPAL INVESTIGATOR

• Stephen K Liu, MD

  Memorial Medical Center - Modesto

  PRINCIPAL INVESTIGATOR

• Immad Sidiq, MD

  Hartford Hospital

  PRINCIPAL INVESTIGATOR

• Samuel Z Goldhaber, MD

  Brigham and Women's

  STUDY CHAIR

• Mark J Garcia, MD

  Christiana Hospital

  PRINCIPAL INVESTIGATOR

• Rohit Bhatheja, MD

  AdventHealth

  PRINCIPAL INVESTIGATOR

• Robert Kennedy, MD

  Holmes Regional Medical Center

  PRINCIPAL INVESTIGATOR

• Fakhir Elmasri, MD

  Lakeland Regional Medical Center

  PRINCIPAL INVESTIGATOR

• Barry S Weinstock, MD

  Orlando Regional Medical Center

  PRINCIPAL INVESTIGATOR

• Juan Ayerdi, MD

  Medical Center of Central Georgia

  PRINCIPAL INVESTIGATOR

• Nilesh Goswami, MD

  Prairie Heart Institute - St.John's Hospital

  PRINCIPAL INVESTIGATOR

• Kannan Natarajan, MD

  St Vincent's Hospital

  PRINCIPAL INVESTIGATOR

• Tod C Engelhardt, MD

  East Jefferson General Hospital

  PRINCIPAL INVESTIGATOR

• Mark Kumar, MD

  Overlook Medical Center

  PRINCIPAL INVESTIGATOR

• John Rundback, MD

  Holy Name Hospital

  PRINCIPAL INVESTIGATOR

• Jacob Cynamon, MD

  Montefiore Medical Center

  PRINCIPAL INVESTIGATOR

• Peter Soukas, MD

  The Miriam Hospital

  PRINCIPAL INVESTIGATOR

• Mohammad L Raja, MD

  Providence Memorial Hospital - Sierra Vista Hospital

  PRINCIPAL INVESTIGATOR

• Keith M Sterling, MD

  Inova Alexandria

  PRINCIPAL INVESTIGATOR

• John Gurley, MD

  University of Kentucky

  PRINCIPAL INVESTIGATOR

• Noah Jones, MD

  Mt. Carmel East

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2012
• First Posted: January 20, 2012
• Study Start: June 7, 2012
• Primary Completion: February 17, 2013
• Study Completion: February 17, 2013
• Last Updated: July 19, 2021
• Results First Posted: July 5, 2019

Record last verified: 2021-07

Locations

US (22)