Recurrent or Persistent Device Related Thrombus After Left Atrial Appendage Occlusion: The RE-DRT Study

Thromboembolic Event Clinical Trial

— RE-DRT  

Official title:

Recurrent or Persistent Device Related Thrombus After Left Atrial Appendage Occlusion: The RE-DRT Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06177704
• Other study ID #: RE-DRT
• Status: Not yet recruiting
• Start date: June 1, 2024
• Est. completion date: January 1, 2028

Study information

• Verified date: May 2024
• Source: Institut universitaire de cardiologie et de pneumologie de Québec, University Laval
• Contact: Josep Rodes-Cabau, MD, PhD
• Phone: 14186568711
• Email: josep.rodes[@]criucpq.ulaval.ca
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study is a prospective, multicenter international trial aimed at assessing the actual incidence, identifying associated factors, and evaluating the clinical consequences of both persistent and recurrent device-related thrombus (DRT) following percutaneous left atrial appendage occlusion (LAAO).

While LAAO has shown efficacy in reducing the risk of stroke, device-related thrombus (DRT) remains a significant concern. The reported incidence of DRT varies, and it is associated with an elevated risk of ischemic stroke and death. The study highlights that persistent and recurrent DRT pose higher risks of thromboembolic events, and current data come from retrospective studies with non-standardized imaging follow-up protocols. The timing of imaging follow-up is crucial, and the study notes discrepancies in recommendations from expert statements. The EHRA/EAPCI suggests imaging at specific intervals post-procedure, while the SCAI/HRS recommends repeat imaging at shorter intervals to assess DRT resolution. The study underscores the need for dedicated prospective data to accurately determine the incidence, factors, and clinical impact of persistent and recurrent DRT after LAAO.

Description:

BACKGROUND: Percutaneous left atrial appendage occlusion (LAAO) has emerged as a nonpharmacological alternative for stroke prevention in patients with non-valvular atrial fibrillation ineligible for chronic anticoagulation therapy. Large real-world observational studies have consistently reported the efficacy of LAAO in reducing the risk of ischemic stroke and systemic embolism, compared to predicted rates, without the need for anticoagulants. Despite ongoing refinement in LAAO procedural technique, significant challenges persist. Notably, device-related thrombus (DRT) remains the main concern after LAAO. The reported incidence rate varies, ranging from 3% to 7%, and has been associated with an elevated risk of ischemic stroke and all-cause death following LAAO. Several risk factors have been identified with DRT occurrence, most of which are non-modifiable. The diagnosis of DRT is followed by an intensification of the antithrombotic treatment. However, not all DRT are resolved, with a significant number persisting or recurring upon withdrawal of anticoagulation therapy. In these situations, the antithrombotic treatment must be maintained, increasing the risk of bleeding, and mitigating the potential benefits of LAAO.

Both persistent and recurrent DRT have been linked to an increased risk of thromboembolic events when compared to resolved DRT. In the pooled analysis of data from the PROTECT-AF and PREVAIL trials, around 12% of embolic events in patients with DRT occurred in the presence of multiple DRT episodes. The incidence of persistent DRT has been reported in one out of three patients diagnosed with DRT, with DRT recurrence occurring in one out of five patients. However, the real incidence of persistent and recurrent DRT is uncertain, as current data come from retrospective studies with non-standardized imaging follow-up protocols. This situation leads to a significant number of missed cases, increases the risk of bias, and likely underestimates the rate of persistent and recurrent DRT. The timing of the imaging follow-up can significantly affect the incidence of DRT. In consecutive patients examined through a pre-specified protocol, the incidence of specific findings would be much more accurate compared to imaging examinations based exclusively on a single adverse clinical event, where the real incidence and clinical associations cannot be accurately determined.

The EHRA/EAPCI expert LAAO statement recommends imaging within 6-24 weeks and then 12 months post-procedure, with no mention of imaging follow-up in case of persistent or recurrent DRT. In contrast, the recent SCAI/HRS expert consensus statement on transcatheter LAAO suggests that repeat imaging at 45- to 90-day intervals can be conducted to assess for DRT resolution and consider the eventual cessation of anticoagulation, although there is no evidence that support this recommendation. Finally, considering the substantial rate of recurrent DRT and its clinical implications, a long-term and sequential imaging follow-up strategy may be warranted. Therefore, there is an unmet need for dedicated prospective data to determine the real incidence, related factors, and clinical impact of persistent and recurrent DRT after LAAO.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: January 1, 2028
• Est. primary completion date: January 1, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients with diagnosis of probable/definite DRT after LAAO detected by transesophageal echocardiography (TEE) or cardiac computed tomography (CT).

• Age=18 years old.

Exclusion Criteria:

• Unable to provide informed consent

Related Conditions & MeSH terms

• Thromboembolic Event
• Thromboembolism
• Thrombosis

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Institut universitaire de cardiologie et de pneumologie de Québec, University Laval

References & Publications (13)

Alkhouli M, Alarouri H, Kramer A, Korsholm K, Collins J, De Backer O, Hatoum H, Nielsen-Kudsk JE. Device-Related Thrombus After Left Atrial Appendage Occlusion: Clinical Impact, Predictors, Classification, and Management. JACC Cardiovasc Interv. 2023 Nov — View Citation

Alkhouli M, Busu T, Shah K, Osman M, Alqahtani F, Raybuck B. Incidence and Clinical Impact of Device-Related Thrombus Following Percutaneous Left Atrial Appendage Occlusion: A Meta-Analysis. JACC Clin Electrophysiol. 2018 Dec;4(12):1629-1637. doi: 10.1016 — View Citation

Asmarats L, Cruz-Gonzalez I, Nombela-Franco L, Arzamendi D, Peral V, Nietlispach F, Latib A, Maffeo D, Gonzalez-Ferreiro R, Rodriguez-Gabella T, Agudelo V, Alamar M, Ghenzi RA, Mangieri A, Bernier M, Rodes-Cabau J. Recurrence of Device-Related Thrombus Af — View Citation

Glikson M, Wolff R, Hindricks G, Mandrola J, Camm AJ, Lip GYH, Fauchier L, Betts TR, Lewalter T, Saw J, Tzikas A, Sternik L, Nietlispach F, Berti S, Sievert H, Bertog S, Meier B; ESC Scientific Document Group. EHRA/EAPCI expert consensus statement on cath — View Citation

Holmes DR Jr, Korsholm K, Rodes-Cabau J, Saw J, Berti S, Alkhouli MA. Left atrial appendage occlusion. EuroIntervention. 2023 Feb 6;18(13):e1038-e1065. doi: 10.4244/EIJ-D-22-00627. — View Citation

Holmes DR Jr, Reddy VY, Gordon NT, Delurgio D, Doshi SK, Desai AJ, Stone JE Jr, Kar S. Long-Term Safety and Efficacy in Continued Access Left Atrial Appendage Closure Registries. J Am Coll Cardiol. 2019 Dec 10;74(23):2878-2889. doi: 10.1016/j.jacc.2019.09 — View Citation

Mesnier J, Cepas-Guillen P, Freixa X, Flores-Umanzor E, Hoang Trinh K, O'Hara G, Rodes-Cabau J. Antithrombotic Management After Left Atrial Appendage Closure: Current Evidence and Future Perspectives. Circ Cardiovasc Interv. 2023 May;16(5):e012812. doi: 1 — View Citation

Mesnier J, Simard T, Jung RG, Lehenbauer KR, Piayda K, Pracon R, Jackson GG, Flores-Umanzor E, Faroux L, Korsholm K, Chun JKR, Chen S, Maarse M, Montrella K, Chaker Z, Spoon JN, Pastormerlo LE, Meincke F, Sawant AC, Moldovan CM, Qintar M, Aktas MK, Branca L, Radinovic A, Ram P, El-Zein RS, Flautt T, Ding WY, Sayegh B, Benito-Gonzalez T, Lee OH, Badejoko SO, Paitazoglou C, Karim N, Zaghloul AM, Agarwal H, Kaplan RM, Alli O, Ahmed A, Suradi HS, Knight BP, Alla VM, Panaich SS, Wong T, Bergmann MW, Chothia R, Kim JS, Perez de Prado A, Bazaz R, Gupta D, Valderrabano M, Sanchez CE, El Chami MF, Mazzone P, Adamo M, Ling F, Wang DD, O'Neill W, Wojakowski W, Pershad A, Berti S, Spoon DB, Kawsara A, Jabbour G, Boersma LVA, Schmidt B, Nielsen-Kudsk JE, Freixa X, Ellis CR, Fauchier L, Demkow M, Sievert H, Main ML, Hibbert B, Holmes DR Jr, Alkhouli M, Rodes-Cabau J. Persistent and Recurrent Device-Related Thrombus After Left Atrial Appendage Closure: Incidence, Predictors, and Outcomes. JACC Cardiovasc Interv. 2023 Nov 27;16(22):2722-2732. doi: 10.1016/j.jcin.2023.09.017. — View Citation

Reddy VY, Doshi SK, Kar S, Gibson DN, Price MJ, Huber K, Horton RP, Buchbinder M, Neuzil P, Gordon NT, Holmes DR Jr; PREVAIL and PROTECT AF Investigators. 5-Year Outcomes After Left Atrial Appendage Closure: From the PREVAIL and PROTECT AF Trials. J Am Co — View Citation

Saw J, Holmes DR, Cavalcante JL, Freeman JV, Goldsweig AM, Kavinsky CJ, Moussa ID, Munger TM, Price MJ, Reisman M, Sherwood MW, Turi ZG, Wang DD, Whisenant BK. SCAI/HRS expert consensus statement on transcatheter left atrial appendage closure. Heart Rhythm. 2023 May;20(5):e1-e16. doi: 10.1016/j.hrthm.2023.01.007. Epub 2023 Mar 27. — View Citation

Sedaghat A, Vij V, Al-Kassou B, Gloekler S, Galea R, Furholz M, Meier B, Valgimigli M, O'Hara G, Arzamendi D, Agudelo V, Asmarats L, Freixa X, Flores-Umanzor E, De Backer O, Sondergaard L, Nombela-Franco L, McInerney A, Korsholm K, Nielsen-Kudsk JE, Afzal — View Citation

Simard TJ, Hibbert B, Alkhouli MA, Abraham NS, Holmes DR Jr. Device-related thrombus following left atrial appendage occlusion. EuroIntervention. 2022 Jun 24;18(3):224-232. doi: 10.4244/EIJ-D-21-01010. — View Citation

Tzikas A, Holmes DR Jr, Gafoor S, Ruiz CE, Blomstrom-Lundqvist C, Diener HC, Cappato R, Kar S, Lee RJ, Byrne RA, Ibrahim R, Lakkireddy D, Soliman OI, Nabauer M, Schneider S, Brachmann J, Saver JL, Tiemann K, Sievert H, Camm AJ, Lewalter T. Percutaneous left atrial appendage occlusion: the Munich consensus document on definitions, endpoints, and data collection requirements for clinical studies. Europace. 2017 Jan;19(1):4-15. doi: 10.1093/europace/euw141. Epub 2016 Aug 18. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Thromboembolic events (ischemic stroke, systemic embolism)	Incidence of and thromboembolic events (ischemic stroke, systemic embolism) associated with persistent/recurrent DRT after LAAO	1-month, 6-month, 1-year, 2-year