Optimum Duration of Acoustic Pulse Thrombolysis Procedure in Acute Pulmonary Embolism

NCT ID: NCT02396758

Last Updated: 2021-07-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 131 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-06-12
• Study Completion Date: 2020-01-30

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.

Detailed Description

This study is designed to investigate the lowest recombinant tissue plasminogen activator (r-tPA) dose-ultrasound treatment time required to achieve the same reductions in thrombus burden and associated improvement in physiologic parameters demonstrated in ULTIMA (EKOS 08 [NCT01166997]) and SEATTLE II (EKOS 09 [NCT01513759]). Results of this study are intended to inform the study design for further studies of the Acoustic Pulse Thrombolysis (APT) Procedure. Analysis of the first 100 evaluable participants in the United States study suggested a degree of equipoise between treatment groups 1, 2 and 3 of the protocol and therefore the sample size has been extended and additional sites in the United Kingdom (UK) National Health Service included, with a view to adding to the findings of the OPTALYSE study from sites in the UK and increasing the number of participants treated by treatment protocol.

Conditions

Pulmonary Embolism and Thrombosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

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.

Group Type: EXPERIMENTAL

Ekosonic® Endovascular Device ultrasonic infusion catheter

Intervention Type: DEVICE

r-tPA will be administered via EKOS.

Recombinant tissue plasminogen activator

Intervention Type: BIOLOGICAL

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

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

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.

Group Type: EXPERIMENTAL

Ekosonic® Endovascular Device ultrasonic infusion catheter

Intervention Type: DEVICE

r-tPA will be administered via EKOS.

Recombinant tissue plasminogen activator

Intervention Type: BIOLOGICAL

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

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

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.

Group Type: EXPERIMENTAL

Ekosonic® Endovascular Device ultrasonic infusion catheter

Intervention Type: DEVICE

r-tPA will be administered via EKOS.

Recombinant tissue plasminogen activator

Intervention Type: BIOLOGICAL

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

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

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.

Group Type: EXPERIMENTAL

Ekosonic® Endovascular Device ultrasonic infusion catheter

Intervention Type: DEVICE

r-tPA will be administered via EKOS.

Recombinant tissue plasminogen activator

Intervention Type: BIOLOGICAL

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

Interventions

Ekosonic® Endovascular Device ultrasonic infusion catheter

r-tPA will be administered via EKOS.

Intervention Type: DEVICE

Recombinant tissue plasminogen activator

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

Intervention Type: BIOLOGICAL

Other Intervention Names

Acoustic Pulse Thrombolysis Procedure (APT Procedure); EKOS; r-tPA

Eligibility Criteria

Inclusion Criteria

1. Male or female greater than or equal to (≥) 18 years of age and less than or equal to (≤) 75 years of age.

2. CTA evidence of proximal PE (filling defect in at least one main or lobar pulmonary artery).

3. PE symptom duration ≤14 days.

4. 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.

5. Must be treated within 48 hours of diagnosis of PE by CTA.

6. Signed Informed consent obtained from subject or Legally Authorized Representative.

Exclusion Criteria

1. Stroke or transient ischemic attack (TIA), head trauma, or other active intracranial or intraspinal disease within one year.

2. Recent (within one month) or active bleeding from a major organ.

3. Major surgery within seven days of screening for study enrollment.

4. Clinician deems the subject high-risk for catastrophic bleeding.

5. History of heparin-induced thrombocytopenia (HIT).

6. Catheter-based pharmacomechanical treatment for PE within 3 days of study enrollment.

7. Systolic blood pressure (SBP) less than 90 mm Hg and/or use of vasopressors.

8. Cardiac arrest (including pulseless electrical activity and asystole) requiring active cardiopulmonary resuscitation (CPR).

9. Evidence of irreversible neurological compromise.

10. Life expectancy < one year. For Participants in UK Sites: Life expectancy < one year or enrollment in hospice care.

11. Use of thrombolytics or glycoprotein IIb/IIIa antagonists within 3 days prior to inclusion in the study.

12. Out-of-Range Laboratory Values: Hematocrit < 30%, Platelets < 100 thousand/microliter (μL), International normalized ratio (INR) > 3.

13. Creatinine outside the normal range for the treating institution.

14. Participant is pregnant (positive pregnancy test; women of childbearing capacity must be tested) or breast feeding.

15. 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.

16. 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.

17. History of any hematologic disease potentially involving abnormal platelet number or function.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

EKOS Corporation

INDUSTRY

Sponsor Role: collaborator

Boston Scientific Corporation

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Victor Tapson, MD

Role: PRINCIPAL_INVESTIGATOR

Cedar Sinai, Los Angeles

Locations

Cedars Sinai

Beverly Hills, California, United States

Tallahassee Memorial Hospital

Tallahassee, Florida, United States

Florida Hospital Tampa

Tampa, Florida, United States

Piedmont Hospital

Atlanta, Georgia, United States

University Hospital

Augusta, Georgia, United States

St. Vincent Medical Group

Indianapolis, Indiana, United States

Jewish Hospital

Louisville, Kentucky, United States

East Jefferson General Hospital

Metairie, Louisiana, United States

Detroit Medical Center

Detroit, Michigan, United States

Mount Carmel Health System

Columbus, Ohio, United States

UPMC Hamot

Erie, Pennsylvania, United States

Lankenau Medical Center

Wynnewood, Pennsylvania, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Houston Methodist Sugarland Hospital

Richmond, Texas, United States

Inova Alexandria Hospital

Alexandria, Virginia, United States

Providence Sacred Heart Medical Center

Spokane, Washington, United States

Royal Devon & Exeter Hospital

Exeter, England, United Kingdom

Medway Maritime Hospital

Gillingham, England, United Kingdom

Royal Free Hospital

London, England, United Kingdom

St. Thomas Hospital

London, England, United Kingdom

Ninewells Hospital

Dundee, Scotland, United Kingdom

Countries

United States; United Kingdom

References

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.

Reference Type: BACKGROUND

PMID: 32757658 (View on PubMed)

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.

Reference Type: RESULT

PMID: 30025734 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-000502-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EKOS-12

Identifier Type: -

Identifier Source: org_study_id