Author + information
- Received December 1, 2017
- Revision received March 26, 2018
- Accepted April 3, 2018
- Published online July 16, 2018.
- Victor F. Tapson, MDa,∗ (, )
- Keith Sterling, MDb,
- Noah Jones, MD, MPHc,
- Mahir Elder, MDd,
- Uttam Tripathy, MDe,
- Jayson Brower, MDf,
- Robert L. Maholic, DOg,
- Charles B. Ross, MDh,
- Kannan Natarajan, MDi,
- Pete Fong, MDj,
- Lee Greenspon, MDk,
- Houman Tamaddon, MDl,
- Amir R. Piracha, MDm,
- Tod Engelhardt, MDn,
- John Katopodis, MDo,
- Vasco Marques, MDp,
- Andrew S.P. Sharp, MDq,
- Gregory Piazza, MD, MSr and
- Samuel Z. Goldhaber, MDr
- aPulmonary/Critical Care Division, Cedars-Sinai Medical Center, Los Angeles, California
- bCardiovascular & Interventional Radiology, Inova Alexandria Hospital, Alexandria, Virginia
- cMount Carmel Health System, Columbus, Ohio
- dDetroit Medical Center/Wayne State University School of Medicine, Detroit, Michigan
- eHouston Methodist Sugarland Hospital, Sugarland, Texas
- fProvidence Sacred Heart Medical Center, Spokane, Washington
- gUPMC-Hamot Heart and Vascular Institute, Erie, Pennsylvania
- hPiedmont Atlanta Hospital, Piedmont Heart, Atlanta, Georgia
- iSt. Vincent Hospital and Health Care Center, Indianapolis, Indiana
- jVanderbilt Heart and Vascular Institute, Vanderbilt University Medical Center, Nashville, Tennessee
- kPulmonary Critical Care Division, Lankenau Medical Center, Wynnewood, Pennsylvania
- lUniversity Hospital, Augusta, Georgia
- mJewish Hospital, Kentucky One Health Cardiology Associates, Louisville, Kentucky
- nEast Jefferson General Hospital, Metairie, Louisiana
- oTallahassee Memorial Hospital, Tallahassee, Florida
- pFlorida Hospital, Tampa, Florida
- qRoyal Devon & Exeter NHS Foundation Trust and University of Exeter, Exeter, United Kingdom
- rCardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
- ↵∗Address for correspondence:
Dr. Victor F. Tapson, Pulmonary Critical Care Medicine, Cedars-Sinai Medical Center, Room W155 Thalians Building, 8730 Alden Drive, Los Angeles, California 90048.
Objectives The aim of this study was to determine the lowest optimal tissue plasminogen activator (tPA) dose and delivery duration using ultrasound-facilitated catheter-directed thrombolysis (USCDT) for the treatment of acute intermediate-risk (submassive) pulmonary embolism.
Background Previous trials of USCDT used tPA over 12 to 24 h at doses of 20 to 24 mg for acute pulmonary embolism.
Methods Hemodynamically stable adults with acute intermediate-risk pulmonary embolism documented by computed tomographic angiography were randomized into this prospective multicenter, parallel-group trial. Patients received treatment with 1 of 4 USCDT regimens. The tPA dose ranged from 4 to 12 mg per lung and infusion duration from 2 to 6 h. The primary efficacy endpoint was reduction in right ventricular–to–left ventricular diameter ratio by computed tomographic angiography. A major secondary endpoint was embolic burden by refined modified Miller score, measured on computed tomographic angiography 48 h after initiation of USCDT.
Results One hundred one patients were randomized, and improvements in right ventricular–to–left ventricular diameter ratio were as follows: arm 1 (4 mg/lung/2 h), 0.40 (24%; p = 0.0001); arm 2 (4 mg/lung/4 h), 0.35 (22.6%; p = 0.0001); arm 3 (6 mg/lung/6 h), 0.42 (26.3%; p = 0.0001); and arm 4 (12 mg/lung/6 h), 0.48 (25.5%; p = 0.0001). Improvement in refined modified Miller score was also seen in all groups. Four patients experienced major bleeding (4%). Of 2 intracranial hemorrhage events, 1 was attributed to tPA delivered by USCDT.
Conclusions Treatment with USCDT using a shorter delivery duration and lower-dose tPA was associated with improved right ventricular function and reduced clot burden compared with baseline. The major bleeding rate was low, but 1 intracranial hemorrhage event due to tPA delivered by USCDT did occur.
This research study was funded by Ekos/BTG. Dr. Tapson served as the principal investigator for the trial; has received research support from BiO2 Medical, Bayer, Ekos/BTG, Daiichi-Sankyo, Inari, Janssen, and Portola; has received consulting fees from Bayer and Janssen; and serves as president of the U.S. Pulmonary Response Team Consortium. Dr. Sterling has received research funding from Ekos/BTG, Penumbra, and Angiodynamics; and consulting fees from Ekos/BTG and Boston Scientific. Dr. Jones has received consulting fees from Medtronic, Edwards Lifesciences, St. Jude Medical, Cordis, Ekos/BTG, and Abbott; and speaking honoraria from Ekos/BTG and Abbott. Dr. Elder has received consulting fees and speaking honoraria from Ekos/BTG. Dr. Brower has received consulting fees from Sirtex, Merit Medical, and Ekos/BTG. Dr. Maholic has received consulting fees from Ekos/BTG; speaking honoraria from Abbott Vascular; and serves on the Pulmonary Embolism Response Team Consortium Board of Directors. Dr. Ross has received consulting fees from Zimmer Biomet. Dr. Natarajan has received research support from Cook Medical; and consulting fees from BTG, CSI, Abbott, Gore, and Cook Medical. Dr. Tamaddon has received consulting fees and speaking honoraria from Cook Medical. Dr. Piracha has received speaking honoraria from Novartis, Janssen, and AstraZeneca. Dr. Englehart has received speaking honoraria from Ekos/BTG, Gore, and Janssen. Dr. Marques has received consulting fees from Medtronic. Dr. Sharp has received research support, consulting fees, and speaking honoraria from Ekos/BTG. Dr. Piazza has received research support from Ekos/BTG, Bristol-Myers Squibb, Daiichi-Sankyo, and Janssen; and serves on the scientific advisory panel for Portola. Dr. Goldhaber has received research support from BiO2 Medical, Bayer, Ekos/BTG, Daiichi-Sankyo, Inari, Janssen, and Portola; and consulting fees from Bayer and Janssen. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received December 1, 2017.
- Revision received March 26, 2018.
- Accepted April 3, 2018.
- 2018 The Authors