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Clinical Trials/NCT03389971
NCT03389971CompletedNot Applicable

ULTRAsound-assisted Catheter vs. STAndaRd Catheter Thrombolysis for Submassive Pulmonary Embolism

Piedmont Healthcare2 sites in 1 country10 target enrollmentStarted: December 6, 2017Last updated:
Conditions

Trial Snapshot

Phase
Not Applicable
Status
Completed
Enrollment
10
Locations
2
Primary Endpoint
thrombus load reduction

Study Overview

Brief Summary

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 infusion catheter 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 lysis utilizing a system of local ultrasound to dissociate the fibrin matrix of the thrombus with simultaneous acoustic streaming of the thrombolytic agent, allowing more efficient thrombolysis. However, there is limited comparative effectiveness data against standard multi-side hole catheter infusion. More rapid clearance of pulmonary thrombus by USAT compared to standard CDT may prove to be clinically beneficial and cost effective. Alternatively, if thrombus clearance is similar, the cost of USAT may exceed the cost of CDT (equipment and disposables), without realization any advantage.

Detailed Description

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. 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. CTEPH 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%).11 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.

Study Design

Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel
Primary Purpose
Treatment
Masking
None

Eligibility Criteria

Ages
18 Years to 80 Years (Adult, Older Adult)
Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Patients with submassive 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) and without the need of catecholamine support or cardiopulmonary resuscitation)

Exclusion Criteria

  • <18 or >80
  • 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

Outcomes

Primary Outcomes

thrombus load reduction

Time Frame: 12 months post surgery

Determine differences in the percentage of thrombus load reduction from baseline to the termination of lysis between the two techniques

Secondary Outcomes

  • cardiopulmonary and clinical outcomes - hemodynamic(12 months post surgery)
  • cardiopulmonary and clinical outcomes - echocardiographic(12 months post surgery)
  • cardiopulmonary and clinical outcomes - respiratory(12 months post surgery)
  • PE QOL(12 months post surgery)
  • utilization cost(12 months post surgery)
  • cardiopulmonary and clinical outcomes - decompensation(12 months post surgery)
  • cardiopulmonary and clinical outcomes - ICU stay(12 months post surgery)
  • cardiopulmonary and clinical outcomes - mortality(12 months post surgery)
  • cardiopulmonary and clinical outcomes - complications(12 months post surgery)
  • San Diego Shortness of Breath questionnaire(12 months post surgery)
  • SF36(12 months post surgery)
  • resource utilization(12 months post surgery)

Investigators

Sponsor Class
Other
Responsible Party
Sponsor

Study Sites (2)

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