Clinical trial NCT03086317: Standard vs Ultrasound-assisted Catheter Thrombolysis for Submassive Pulmonary Embolism
Official title: USAT-CDT Trial: Standard vs Ultrasound-assisted Catheter Thrombolysis for Submassive Pulmonary Embolism
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cardiovascular Diseases
Keywords: Pulmonary Medicine
Therapy Evaluation
Lead sponsor: Emory University
Sponsor class: OTHER
First posted: 2017-03-22
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomized to receive one of two treatments for acute, submassive pulmonary embolism.
Primary purpose: TREATMENT

Brief summary: The study is an investigator-initiated trial comparing two different catheters (standard versus ultrasound assisted) for the treatment of acute high risk pulmonary embolism (blood clots in lung arteries with evidence or heart strain). Patients already planned for the procedure will be randomized to standard catheter-directed thrombolysis (CDT) or to ultrasound-assisted catheter thrombolysis (USAT). Both catheters are currently used routinely in practice for the treatment of pulmonary embolism, but it is not known if USAT is superior to standard CDT, the former being much more expensive and more commonly used.

The purpose of the study is to learn about which catheter-directed therapy is more suitable for patients with pulmonary embolism (PE), who are candidates for both standard catheter directed therapy (CDT), and ultrasound-assisted catheter directed therapy (USAT), and to provide information regarding the cost effectiveness of the two different types of treatment. A total of 80 patients are planned to be recruited. All medication administration, procedures or in-hospital tests will be performed as routine clinical practice. The study will compare short term and long term outcomes: resolution of blood clots on CT scan, right ventricular size improvement, quality of life and symptoms at 3 and 12 months, and cost effectiveness.

Detailed description: Acute pulmonary embolism (PE) accounts for 5-10% of in-hospital deaths. Systemic anticoagulation (AC) is the standard of care and thrombolysis is recommended for those at a higher mortality risk. Catheter-directed therapies, mainly standard catheter-directed thrombolysis (CDT) and ultrasound-accelerated thrombolysis (USAT), have been introduced as new, more effective, and safer treatment modalities. USAT is a modification of standard catheter thrombolysis, utilizing a system of local ultrasound to dissociate the fibrin matrix of the thrombus, allowing deeper penetration of lytics. However, there is limited data comparing the two treatments. More rapid clearance of pulmonary thrombus by USAT compared to standard CDT may prove to be more effective regarding clinical outcomes and cost (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 (equipment and disposables), without offering any potential advantage.

This controlled, randomized study seeks to determine if ultrasound acceleration adds any benefits in the outcomes and costs of catheter-directed thrombolysis for patients with acute submassive PE. The treatment with CDT or USAT are standard of care for submassive PE and participants will be randomized to receive one treatment or the other. Participants will have follow up visits at 3 months and 12 months post procedure. All the procedures, tests, and follow up visits are according to current standard of care.

Eligibility criteria: Inclusion Criteria:

* Patients eligible for catheter directed thrombolysis per the study protocol for submassive pulmonary embolism (PE)

  * CT or echocardiographic RV strain (defined as RV/LV ratio \>1)
  * without persisting hypotension \<90mmHg or drop of systolic blood pressure by at least 40mm Hg for at least 15 minutes with signs of end-organ hypoperfusion (cold extremities or low urinary output \<30 mL/h or mental confusion)
* without the need of catecholamine support
* without the need of cardiopulmonary resuscitation

Exclusion Criteria:

* Pregnancy
* Index PE symptom duration \>14 days
* High bleeding risk (any prior intracranial hemorrhage, known structural intracranial cerebrovascular disease or neoplasm, ischemic stroke within 3 months, suspected aortic dissection, active bleeding or bleeding diathesis, recent spinal or cranial/brain surgery, recent closed-head or facial trauma with bony fracture or brain injury)
* Participation in any other investigational drug or device study
* Life expectancy \<90 days
* Inability to comply with study assessments

Primary outcomes:
measure: Percentage of Thrombus Obstruction
timeFrame: Baseline to end of lysis treatment (up to 72 hours)
Secondary outcomes:
measure: In Hospital Mortality
timeFrame: Until hospital discharge (an average of 6 days)
measure: 90-day Mortality
timeFrame: Until 90 days post procedure
measure: Cardiac Decompensation Due to Massive Pulmonary Embolism
timeFrame: Through follow up (12 months)
measure: Major Bleeding
timeFrame: Through follow up (12 months)
measure: Minor Bleeding
timeFrame: Through follow up (12 months)
measure: Symptomatic Venous Thromboembolism (VTE)
timeFrame: Until 90 days post procedure
measure: Clinical Success of Treatment
timeFrame: Until 90 days post procedure
measure: ICU Length of Stay
timeFrame: Until hospital discharge (an average of 6 days)
measure: Change in Right Ventricular/Left Ventricular (RV/LV) Diameter Ratio
timeFrame: Baseline, end of lysis treatment, Month 3, Month 12
measure: Change in Tricuspid Annular Plane Systolic Excursion (TAPSE)
timeFrame: Baseline, end of lysis treatment, Month 3, Month 12
measure: Change in Right Ventricular Systolic Pressure (RVSP)
timeFrame: Baseline, end of lysis treatment, Month 3, Month 12
measure: Number of Participants Who Had a Decrease in New York Heart Association (NYHA) Functional Classification of Heart Failure From Class 4 to Class 2
timeFrame: Month 3, Month 12
measure: Change in 6-minute Walk Test
timeFrame: Month 3, Month 12
measure: Change in 36-Item, Short Form (SF-36) Score
timeFrame: Month 3, Month 12
measure: Change in Quality of Life After Pulmonary Embolism (PEmb QoL) Score
timeFrame: Month 3, Month 12
measure: Change in Shortness of Breath Questionnaire Score
timeFrame: Month 3, Month 12
measure: Cost Effectiveness Analysis
timeFrame: Month 12
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Grady Health System
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital Midtown
state: Georgia
city: Atlanta
country: United States
facility: Emory Clinic
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
Study officials:
affiliation: Emory University
name: Wissam Jaber, MD
role: PRINCIPAL_INVESTIGATOR
References: