A Prospective, Multicenter Study of the Indigo* Aspiration System Seeking to Evaluate the Long-Term Safety and Outcomes of Treating Pulmonary Embolism

Acute massive pulmonary embolism (PE), defined as hemodynamic instability from
acute PE, and acute submassive PE, defined by right ventricular strain without
hypotension, are common life-threatening conditions that represent the serious
manifestations of venous thromboembolic disease. In the United States, an
estimated 530,000 cases of symptomatic PE occur annually;1 and approximately
300,000 people die every year from acute PE.2 The mortality rate can exceed 58%
in patients with acute massive PE presenting with hemodynamic shock,3 and most
of these deaths occur within 1 hour of presentation.2-4 Acute massive PE is
believed to be the third most common cause of death among hospitalized
patients.5
The physiologic effect of massive PE is right ventricular failure, which
reduces left ventricular preload and can lead to systemic hypotension and
sudden death. While submassive PE has a lower mortality than massive PE, it is
associated with a higher mortality and higher rate of clinical deterioration
than low-risk PE. Therapeutic anticoagulation is the standard of care (SOC)
first-line treatment; the 2016 American College of Chest Physicians (ACCP),
2019 European Society of Cardiology (ESC) and 2011 American Heart Association
(AHA) guidelines all recommend the prompt use of anticoagulant therapy (Grade
1b, Class Ia and Class 1a respectively).6-8
Treatment escalation beyond therapeutic anticoagulation is also common
practice. Current approved medical therapy for acute massive PE consists of
systemic thrombolysis with 100 mg of tPA (Alteplase; Genentech, South San
Francisco, California) infused intravenously (IV) over a period of 2 hours.9
Escalating therapy with systemic thrombolytics, while it improves short-term
and potentially long-term PE related adverse outcomes, is associated with high
incidence of major bleeding.
A meta-analysis of 15 trials involving a total of 2057 massive and submassive
PE patients found that major hemorrhage (OR: 2.91; 95% CI: 1.95 to 4.36) and
fatal or intracranial hemorrhage (OR: 3.18; 95% CI: 1.25 to 8.11) was
significantly more frequent among patients receiving thrombolysis.10 An
international registry on massive PE patients who received fibrinolytics and/or
inferior vena cava filter placement reported a 90-day mortality rate of 52.4%
(95% CI, 43.3% to 62.1%).11 The study also concluded that thrombolytics did not
reduce the 90-day mortality rate.11 In another meta-analysis of 8 randomized
trials investigating submassive PE, major bleeding including intracranial
hemorrhage was significantly more common with systemic thrombolytics compared
to anticoagulants alone.12
The optimal treatment strategy for patients with submassive PE is not as clear.
Experts agree that further research is needed to tailor treatment protocols and
to evaluate long-term outcomes. Several studies have shown higher rates of
in-hospital adverse events as well as pulmonary hypertension and poor
functional status at follow-up in high risk submassive PE patients given
anticoagulants alone.12-14
Given the incomplete efficacy of anticoagulation alone and high bleeding
complications of full dose systemic thrombolysis, endovascular
catheter-directed therapy has garnered significant interest. Expert guidelines
differ in exact treatment recommendations for acute PE, but do suggest
catheter-directed therapy - which includes the Indigo Aspiration System - in
certain circumstances.6-8,15
For acute PE, the 2019 ESC guideline states that endovascular treatment should
be considered for patients with high-risk PE and failed or contraindicated
thrombolysis and for patients with intermediate- or low-risk PE who experience
hemodynamic deterioration on anticoagulants (class IIa).8 Percutaneous
mechanical thrombectomy (e.g. aspiration thrombectomy, fragmentation
thrombectomy and rheolytic thrombectomy) procedures were graded in the 2011 AHA
guidelines as class IIa and in the 2016 ACCP guidelines as class II.6,7 The
2019 AHA scientific statement noted that interventional therapies should be
strongly considered in patients with PE and hemodynamic instability, and that
catheter-based embolectomy is an option for intermediate risk patients with
elevated risk for decompensation and bleeding.15 Thus, catheter-directed
therapy should be considered for acute massive PE patients who are not
candidates for or who fail systemic thrombolysis, and for the more unstable
subset of all other acute PE patients.6-8
Catheter-directed therapy encompasses catheter-directed mechanical
fragmentation, aspiration of emboli, and intraclot thrombolytic agent direct
local infusion. Therefore, a variety of devices may be used to treat PE.
Depending on anticipated bleeding risk, catheter-directed therapy may be
performed with no or low-dose local tPA injection. The goal of these techniques
is to rapidly debulk central thrombus to relieve life-threatening heart strain,
immediately improve pulmonary perfusion and reduce the risk of mortality and
clinical deterioration.
Catheter intervention is important not only for creating an immediate flow
channel through the obstruction, but also for exposing a greater surface area
of thrombus to the locally infused thrombolytic drug. In a meta-analysis of 594
patients with acute massive PE treated with catheter-directed therapy, clinical
success was achieved in 86.5% of the cases, with success defined as hemodynamic
stabilization, resolution of hypoxia and survival to hospital discharge.16 In
the same study, 33% of cases were initiated with mechanical treatment alone
without local thrombolytic infusion.16 When injected locally, the required dose
of tPA is lower compared with full-dose systemic infusion, potentially reducing
the bleeding risk.

The objective of this study is to evaluate real world long-term functional
outcomes, safety and performance of the Indigo Aspiration System for the
treatment of pulmonary embolism (PE)

Post-market, real world, prospective, multi-center study that will enroll
approximately 1500 subjects at up to 80 sites globally

not applicable