Comparison of Standard CDT vs. USAT for Patients With Acute Submassive PE

2016-05-02 22:08:21 | BioPortfolio


The study will compare standard catheter directed thrombolysis to ultrasound accelerated thrombolysis for the treatment of acute submassive pulmonary embolism (PE). The study population will include patients eligible for catheter directed thrombolysis (CDT) for submassive PE. Subjects will be randomized to, either, standard catheter-directed thrombolysis or ultrasound-accelerated thrombolysis (USAT).


Acute pulmonary embolism (PE) carries a high morbidity and is the third-leading cause of cardiovascular mortality in the western world. It accounts for 5-10% of in-hospital deaths that for the United States translates to 200,000 deaths per year.1 Recent registries and cohort studies suggest that approximately 10% of all patients with acute PE die during the first 1 to 3 months after diagnosis. Studies that have observed survivors for >3 months have reported an incidence of chronic thromboembolic pulmonary hypertension (CTEPH) 1-5% within 2-3 years after PE.6-10 It is an incapacitating long-term complication of thromboembolic disease with a negative impact on the patient's quality of life and prognosis.

The management acute PE is mainly guided by the acuity and severity of clinical presentation. Initial systemic anticoagulation (AC) is the standard of care and treatment is escalated based on the clinical presentation and patient characteristics that may stratify them at a higher mortality risk. The goals of therapy are to primarily prevent mortality, and secondarily potentially prevent late onset chronic thromboembolic pulmonary hypertension (CTEPH) and improve quality of life.

Massive PE is defined as PE associated with sustained hemodynamic instability, whereas submassive PE (sPE) is defined as PE without hemodynamic instability but with abnormal right ventricular (RV) function and/or evidence of myocardial necrosis. It is notable that there is ongoing interest to accurately risk stratify sPE to identify the patients who are at increased risk of decompensating and/or dying. Clinical scores, imaging tests and biomarkers are under investigation, yet an ideal prognostic tool is still pending. A novel cardiac biomarker, heart-type fatty acid-binding protein (h-FABP), is emerging as a significant predictor of mortality in patients with submassive PE.

Systemic intravenous thrombolysis is universally recommended by all guideline bodies for massive pulmonary embolism, but remains controversial for submassive PE. In the most recent metaanalysis, the subgroup analysis of 8 submassive PE trials (1993-2014, n=1775) showed that thrombolytic therapy was associated with a mortality reduction (1.39% vs 2.92%) but with an increase in major bleeding (7.74% vs 2.25%). These results were mainly driven by the largest randomized trial (PEITHO, 1006 patients) which compared a single, weight-adapted i.v. bolus of tenecteplase with standard anticoagulation.

The recent development of catheter-directed therapies such as catheter-directed thrombolysis (CDT), ultrasound-accelerated thrombolysis (USAT), and pharmacomechanical or aspiration thrombectomy has introduced more tools for the treatment of acute PE. Proponents of these techniques suggest that they may provide a similar therapeutic benefit as systemic thrombolysis, while decreasing the dose of thrombolytic required and potentially decreasing the risk of adverse bleeding events. Both the American Heart Association and more recently European Society of Cardiology have acknowledged CDT as a viable treatment alternative for high risk acute sPE (echocardiographic RV dysfunction and elevated cardiac biomarkers), if appropriate expertise is available and particularly when the bleeding risk is high.

Catheter-directed thrombolysis requires placement of a multi-sidehole infusion catheter within the pulmonary arterial thrombus burden under angiographic guidance. Thrombolytic medications are slowly infused through the catheter, which is left in place for the duration of the treatment. USAT is a modification of this therapy utilizing a proprietary system of local high frequency, low-power ultrasound to dissociate the fibrin matrix of the thrombus, allowing deeper penetration of lytic medication.

Several observational non-controlled series have demonstrated the efficacy of catheter-directed techniques in improving clinical and hemodynamic parameters and reducing clot burden while demonstrating a favorable safety profile. The ULTIMA trial was the first randomized controlled trial to include CDIs for sPE comparing standardized fixed-dose of USAT (10mg rtPA per lung over 15 hours) and AC to AC alone. In the USAT group, but not in the heparin group, the mean RV/LV ratio was significantly reduced at 24 hours, but became comparable between the two groups at 90 days. The RV systolic function was significantly improved in the USAT group vs. the heparin group at both 24 hours and 90 days. In both study groups minor bleeding complications were rare and there were no major bleeding complications. The SEATTLE II trial, a single-arm study evaluating the effectiveness of USAT, showed also an RV/LV ratio improvement at 48 hours.

Limited data exists for comparing different catheter-directed therapies for acute PE. The majority of recent series for catheter-directed interventions utilize USAT exclusively; however there is limited comparative effectiveness data comparing this modality to standard multi-sidehole catheter infusion. Preliminary, non-controlled data are conflicting. One series by Lin and colleagues of 33 high-risk PE patients suggested benefit for USAT for angiographic clearance of thrombus burden with more bleeding events in the CDT group.31 Kuo and colleagues noted no difference in outcomes and treatment specifics between USAT and CDT in the recently published early results of a multicenter prospective registry. Our retrospective analysis of 63 patients suggests that there may be no difference between the two treatment modalities, demonstrating similar rates of outcomes such as survival, hemodynamic stabilization, and echocardiographic parameters in both groups with similar procedure length and lytic dose in the time-adjusted cohorts. Selection bias cannot be underestimated in all these studies.

The expected benefit of USAT has been dependent on the device's ability to increase penetration of lytic into thrombus using high frequency, low power ultrasound, due to its reversible effects on fibrin dissociation. This benefit has been shown to result in faster thrombus clearance in selected vascular beds in some studies, such as the recently published DUET study comparing USAT and CDT in arterial occlusions. More rapid clearance of pulmonary thrombus by USAT compared to standard CDT may prove to be clinically and cost effective (e.g. via reduced length of ICU and hospital stay). Alternatively, if thrombus clearance is similar, the cost of USAT may exceed the cost of CDT (proprietary equipment and disposables), without offering any potential advantage. Evidence from the venous circulation, coming from the recent BERNUTIFUL trial demonstrated no difference in time to thrombus clearance in lower extremity deep venous thrombosis.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment


Pulmonary Embolism


CDT without ultrasound acceleration, CDT with ultrasound acceleration


Not yet recruiting


University of Pittsburgh

Results (where available)

View Results


Published on BioPortfolio: 2016-05-02T22:08:21-0400

Clinical Trials [3703 Associated Clinical Trials listed on BioPortfolio]

Whole Body Periodic Acceleration on Activity and Sleep In Acceleration

Whole-body periodic acceleration (WBPA) is a new, non-invasive, and promising therapy for a diverse and growing list of disorders including cardiovascular disease. During WBPA, patients li...

Use of Bedside Ultrasound in Emergency Department Patients With Concern for Pulmonary Embolism to Reduce CT Imaging

At most institutions, the average patient with clinical concern for PE(pulmonary embolism) will have a CT angiogram(CTA) with contrast of the lungs performed to evaluate for a clot. Howeve...

Diagnosis of Pulmonary Embolism by Doppler Signals

The LDS may contain information of significant diagnostic and physiological value regarding the pulmonary parenchyma and vasculature, as well as the cardio- vascular system in general. In ...

Connect Your Needle to Your Phone to Increase EUS FNA Diagnostic Yield?

Summary Endoscopic ultrasound fine needle aspiration (EUS FNA) is an established and recommended technique for diagnostic of solid pancreatic masses. The accuracy of the technique depends...

Advanced Gravitational Physiology the Lung Under High-G Acceleration

This is a study of advanced lung physiology in altered gravitational conditions, consisting of respiratory measurements in healthy volunteers during high G acceleration on a long-arm human...

PubMed Articles [4679 Associated PubMed Articles listed on BioPortfolio]

Early Versus Delayed Use of Ultrasound-Assisted Catheter-Directed Thrombolysis in Patients With Acute Submassive Pulmonary Embolism.

The effect of early vs delayed use of ultrasound-assisted catheter-directed thrombolysis (USAT) on invasive hemodynamics and in-hospital outcomes in patients with acute submassive pulmonary embolism (...

EXPRESS: Ultrasound-assisted catheter-directed thrombolysis compared with anticoagulation alone for treatment of intermediate-risk pulmonary embolism.

The measurement of tibial acceleration in runners-A review of the factors that can affect tibial acceleration during running and evidence-based guidelines for its use.

Impact loading in runners, assessed by the measurement of tibial acceleration, has attracted substantial research attention. Due to potential injury links, particularly tibial fatigue fractures, tibia...

The Use of Ultrasound Simulators to Strengthen Scanning Skills in Medical Students: A Randomized Controlled Trial.

This study evaluates the use of ultrasound simulators for retaining and improving ultrasound skills acquired in undergraduate ultrasound training.

Congenital Lobar Overinflation: A Rare Enigmatic Lung Lesion on Prenatal Ultrasound and Magnetic Resonance Imaging.

To report the ultrasound (US) features in prenatal cases of suspected congenital pulmonary airway malformation or unspecified lung lesions with a final surgical pathologic diagnosis of congenital loba...

Medical and Biotech [MESH] Definitions

The use of ultrasound to guide minimally invasive surgical procedures such as needle ASPIRATION BIOPSY; DRAINAGE; etc. Its widest application is intravascular ultrasound imaging but it is useful also in urology and intra-abdominal conditions.

Tissue ablation of the PROSTATE performed by ultrasound from a transducer placed in the RECTUM. The procedure is used to treat prostate cancer (PROSTATIC NEOPLASMS) and benign prostatic hypertrophy (PROSTATIC HYPERPLASIA).

Ultrasonography applying the Doppler effect, with frequency-shifted ultrasound reflections produced by moving targets (usually red blood cells) in the bloodstream along the ultrasound axis in direct proportion to the velocity of movement of the targets, to determine both direction and velocity of blood flow. (Stedman, 25th ed)

An increase in the rate of speed.

Hypertrophy and dilation of the RIGHT VENTRICLE of the heart that is caused by PULMONARY HYPERTENSION. This condition is often associated with pulmonary parenchymal or vascular diseases, such as CHRONIC OBSTRUCTIVE PULMONARY DISEASE and PULMONARY EMBOLISM.

More From BioPortfolio on "Comparison of Standard CDT vs. USAT for Patients With Acute Submassive PE"

Quick Search


Relevant Topics

Radiology is the branch of medicine that studies imaging of the body; X-ray (basic, angiography, barium swallows), ultrasound, MRI, CT and PET. These imaging techniques can be used to diagnose, but also to treat a range of conditions, by allowing visuali...

Cardiovascular disease (CVD)
Acute Coronary Syndromes (ACS) Blood Cardiovascular Dialysis Hypertension Stent Stroke Vascular Cardiovascular disease (CVD) includes all the diseases of the heart and circulation including coronary heart disease (angina...

Searches Linking to this Trial