Monica Matsumoto, MS4, University of Chicago Pritzker School of Medicine

Pulmonary embolism (PE) is the leading cause of death from venous thromboembolic (VTE) disease and is an important, preventable source of morbidity and mortality globally1. The incidence of PE has been rising with substantial treatment-associated costs, with the estimated cost per patient to be up to $30,000 annually in the United States 2. Risk factors for PE include both patient-related factors (older age, smoking, obesity, malignancy, oral contraceptives) and setting-related factors (recent surgery, traumatic injury, prolonged immobilization, pregnancy)1,3.

The mainstay of VTE management relies on anticoagulation to prevent both progression and recurrence. However, in patients with an absolute contraindication to anticoagulation, such as intracranial hemorrhage, or in whom anticoagulation has been ineffective, vena cava filters are recommended. Filters have been shown to decrease acute PE recurrence and PE-related mortality3,4. Filters can also be placed prophylactically in certain patient subsets4. In patients meeting the selection criteria, filter placement is most commonly in the inferior vena cava (IVC). However, filters are associated with several long-term complications, even with the increase in use of retrievable devices4. Failure to retrieve non-permanent devices within the appropriate time frame can lead to issues with filter migration, fracture, penetration of the caval wall, and filter thrombosis. Filter retrieval rates vary but remain low, reportedly less than 25%5, and longer indwelling times are associated with higher complications and more difficult retrievals4. Thus, there is utility for temporary filters, those that are placed during high-risk VTE periods and which subsequently undergo bioconversion, to simultaneously decrease the risk of PE while eliminating the long-term complications from indwelling filters.

The study reviewed is a prospective, multi-center, non-randomized clinical trial to assess the safety and efficacy of the Sentry bioconvertible IVC filter (Novate Medical, Galway, Ireland), as a temporary device protecting against PE6.

Study Population and Treatment Protocol

The single-arm SENTRY Clinical Trial (NCT01975090) was conducted at 23 sites in the United States (20), Belgium (2), and Chile (1), from September 2014 to February 2016. The study was sponsored by Novate Medical with an investigational device exemption. Eligibility and exclusion criteria are listed in Table 1. Enrollment criteria were consistent with American College of Radiology (ACR) and Society of Interventional Radiology (SIR) guidelines. Of the 129 enrolled patients, 67.4% (n = 87) had a therapeutic indication for IVC filter placement, and 32.6% (n = 42) had a prophylactic indication.

The Sentry IVC filter is made of cylindrically-framed nitinol with six pairs of arms forming the filter cone, held together in the center by a bioabsorbable filament (poly-p-dioxanone). The central filament hydrolyzes during bioconversion, releasing the arms, which then retract into the IVC wall. The device is intended to provide protection for ≥60 days after placement before the process of bioconversion eventually results in a once again patent IVC.

Table 1. Inclusion and exclusion criteria for enrollment in the SENTRY Clinical Trial
Inclusion Criteria Exclusion Criteria
Age ≥18 Pregnant or planning to be pregnant within 12 months
At temporary (<60 day) risk of PE (as determined by their physician) Serum creatinine ≥ 2.0 mg/dL
Contraindication to or failure of anticoagulation with: documented DVT or PE OR high-risk of developing DVT/PE Life expectancy <12 months
IVC diameter 16-28 mm (as measured in cavogram) Malignancy extending PE period risk to >60 days
Infrarenal IVC length ≥ 9cm Known hypercoagulable state
  Inherited or acquired hemostatic disorder
  Presence of caval stent or IVC filter, or history of IVC filter (<1 month after retrieval)
  Inability to gain femoral or internal jugular vein access
  Infection at only available access site
  Duplicated or left-sided IVC
  Renal vein thrombosis or IVC thrombosis extending to renal veins
  Occlusive or free-floating IVC thrombus
  Known allergy or hypersensitivity to study device materials or to contrast media (not amenable to premedication)

Data Collection and Statistics

Data were reviewed by independent monitoring and case events committees. Patients were evaluated at 1, 2, 6, and 12 months with: (a) clinical assessment of PE/DVT symptoms, (b) adverse event monitoring, and (c) VTE risk factor assessment. The imaging schedule is listed in Table 2. Study end points were in accordance with SIR and ACR guidelines. The primary end point of clinical success at 6 months comprised: (a) composite technical success (successful filter deployment), (b) freedom from symptomatic PE through 60 days, and (c) 6-month freedom from filter-related complications or filter-related death. Secondary efficacy and safety end points evaluated filter configuration, bioconversion, adverse events, and filter-related complications.

The 95 % confidence interval of the observed rate of the primary efficacy endpoint of clinical success, using a Wilson Score Interval, was tested against the SIR trial performance acceptance criteria of greater than ≥80%.

Table 2. Schedule of imaging-intense follow-up in the SENTRY Clinical Trial
Imaging modality Timeframe
Ultrasonography 1 month
Computed tomographic (CT) venography 1 month
Anterior-posterior and lateral x-ray OR CT venography if thrombus observed at 1 month 2 months
CT venography 6 months
Anterior-posterior and lateral x-ray 12 months
CT venography 24 months

Results and Outcomes

The Sentry device was implanted successfully in all 129 enrolled patients. A total of 111 patients (86%) had adequate 12-month follow-up. The primary efficacy endpoint of clinical success at 6-months was achieved in 97.4% of evaluable patients (n = 111, 95% confidence interval: 92.5%-99.1%), exceeding the requisite lower limit of 80%. There was 100% (n = 129) freedom from new symptomatic PE through 60 days, and 98.2% (n = 112/114) freedom from IVC filter-related complications through 6 months, with no additional complications through 12 months. Technical success of deployment was 99.2% (n = 129/130). Device bioconversion was achieved in 95.7% (n = 110/115) and 96.4% (n = 106/110) of patients at 6 and 12 months, respectively. All devices (n = 119) were in filtering configuration at 1-month. Zero deaths were attributed to the filter, and none of the serious adverse events were confirmed as being related to the filter.

Conclusion

The 1-year analysis of the SENTRY clinical trial demonstrated high technical success, positive clinical outcomes, and minimal complications using the bioconvertible Sentry IVC filter. The bioconversion rate is much higher than current rates of IVC filter retrieval, which are insufficient when considering the known complications of indwelling devices. The primary efficacy end point according to SIR criteria was exceeded, advocating for  the placement of the Sentry bioconvertible filter as an alternative to retrievable IVC filters in patients with temporary risk of PE to reduce the complications of extended indwelling times.

Editor: Ranjan Ragulojan, MD

References

1.         Gregson J, Kaptoge S, Bolton T, et al. Cardiovascular Risk Factors Associated With Venous Thromboembolism. JAMA cardiology. 2019;4(2):163-173.

2.         LaMori JC, Shoheiber O, Mody SH, Bookhart BK. Inpatient Resource Use and Cost Burden of Deep Vein Thrombosis and Pulmonary Embolism in the United States. Clinical Therapeutics. 2015;37(1):62-70.

3.         Konstantinides SV, Torbicki A, Agnelli G, et al. 2014 ESC Guidelines on the diagnosis and management of acute pulmonary embolism: The Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC)Endorsed by the European Respiratory Society (ERS). European Heart Journal. 2014;35(43):3033-3080.

4.         Minocha J, Smith AM, Kapoor BS, et al. ACR Appropriateness Criteria® Radiologic Management of Venous Thromboembolism-Inferior Vena Cava Filters. Journal of the American College of Radiology. 2019;16(5, Supplement):S214-S226.

5.         Brown JD, Raissi D, Han Q, Adams VR, Talbert JC. Vena Cava Filter Retrieval Rates and Factors Associated With Retrieval in a Large US Cohort. Journal of the American Heart Association. 2017;6(9):e006708.

6.         Dake MD, Murphy TP, Krämer AH, et al. One-Year Analysis of the Prospective Multicenter SENTRY Clinical Trial: Safety and Effectiveness of the Novate Sentry Bioconvertible Inferior Vena Cava Filter. Journal of Vascular and Interventional Radiology. 2018;29(10):1350-1361.e1354.