# Accelerated Low Dose Thrombolytic Catheter Directed Sonothrombolysis

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2020 · $517,715

## Abstract

Abstract
Venous thromboembolism (VTE), comprising Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE), is
a major health care challenge resulting in significant mortality, morbidity, and societal cost. Annually, there are
approximately 900,000 recurrent, fatal and nonfatal VTE events resulting in 300,000 deaths. In total, annual
direct healthcare expenditures attributable to VTE are $7 – 10 B/yr with an additional $10 – 15B attributable to
premature death and lost productivity caused by both short and long-term disability. Currently, VTE is usually
treated via outpatient management using conventional anticoagulants prevent thrombus extension, pulmonary
embolism and recurrence, but do not dissolve or remove the clot. Approximately half of all patients undergoing
therapy with conventional anticoagulants develop venous dysfunction resulting in post-thrombotic syndrome.
PTS frequently involves: pain, swelling, sensation of heaviness, edema, pigmentation, and deterioration of the
skin, including venous ulcers in severe cases. The key technological advancement proposed involves a new
endovascular approach that accelerates thrombolysis while simultaneously requiring a significantly reduced
dose of thrombolytic drug. The proposed catheter combines local administration of low-dose thrombolytic, in
the immediate vicinity of the blood clot, with adjuvant ultrasound energy and large diameter (~20 m), low sta-
bility microbubbles (MB) that, when exposed to ultrasound, accelerate thrombus dissolution. Using this ap-
proach, we have demonstrated a 4.5x increase in the rate of volumetric clot loss relative to conventional tPA
administration in an in vitro model and enabled a 3.33x tPA dose reduction in a model of ischemic stroke.
After clinical translation (beyond the scope of the current proposal), following large animal trials, “first in hu-
man” and a phased clinical trial, our vision is that a catheter, derivative from that proposed, be used as a direct
substitute for current catheter directed therapy, which frequently requires several days of continuous catheteri-
zation to resolve the thrombus.
 The proposed program of research is organized around the following specific aims:
Specific Aim 1: Develop sonothrombolysis catheter with on-board micro-Coulter microbubble monitoring sys-
tem, high power ultrasound “delivery” transducer and high-resolution transducer for real-time characterization
of thrombolysis progress
Specific Aim 2: Perform an Investigation of ultrasound, thrombolytic drug and microbubbble interactions in a
well-controlled laboratory benchtop in vitro thrombolysis model
Specific Aim 3: Test efficacy of approach in vivo using a murine DVT model

## Key facts

- **NIH application ID:** 9998008
- **Project number:** 5R01HL141752-03
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** John A Hossack
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $517,715
- **Award type:** 5
- **Project period:** 2018-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9998008

## Citation

> US National Institutes of Health, RePORTER application 9998008, Accelerated Low Dose Thrombolytic Catheter Directed Sonothrombolysis (5R01HL141752-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9998008. Licensed CC0.

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