Ignite Creation Date:
2024-05-06 @ 10:54 AM
Last Modification Date:
2024-10-26 @ 12:37 PM
Study NCT ID:
NCT03389971
Status:
COMPLETED
Last Update Posted:
2021-09-24
First Post:
2017-12-06
Brief Title:
ULTRAsound-assisted Catheter vs STAndaRd Catheter Thrombolysis for Submassive Pulmonary Embolism
Sponsor:
Piedmont Healthcare
Organization:
Piedmont Healthcare
Study Overview
Official Title:
ULTRAsound-assisted Catheter vs STAndaRd Catheter Thrombolysis for Submassive Pulmonary Embolism
Status:
COMPLETED
Status Verified Date:
2021-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
UltraStar sPE
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 200000 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 patients 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 andor 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 andor 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 n1775 showed that thrombolytic therapy was associated with a mortality reduction 139 vs 292 but with an increase in major bleeding 774 vs 22511 These results were mainly driven by the largest randomized trial PEITHO 1006 patients which compared a single weight-adapted iv 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 with simultaneous acoustic streaming of the infusate 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 RVLV 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 RVLV 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 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 The University of Pittsburgh groups 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 devices 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 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
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 andor 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 andor 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 n1775 showed that thrombolytic therapy was associated with a mortality reduction 139 vs 292 but with an increase in major bleeding 774 vs 22511 These results were mainly driven by the largest randomized trial PEITHO 1006 patients which compared a single weight-adapted iv 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 with simultaneous acoustic streaming of the infusate 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 RVLV 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 RVLV 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 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 The University of Pittsburgh groups 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 devices 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 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None