Clinical trial NCT04315974: Italian Registry In the Setting of AF Ablation With Rivaroxaban (IRIS)
Official title: Italian Registry In the Setting of AF Ablation With Rivaroxaban
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Atrial Fibrillation
Keywords: Catheter ablation
Rivaroxaban
Real-world clinical practice
Italian registry
Non-valvular Atrial Fibrillation
Lead sponsor: Azienda Policlinico Umberto I
Sponsor class: OTHER
Collaborators: name: Istituto Nazionale per le Ricerche Cardiovascolari (INRC)
First posted: 2020-03-20
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Eligible patients comprise men and women aged 18 years or older with nonvalvular atrial fibrillation (AF) diagnosis undergoing ablation procedure.

250 patients treated with rivaroxaban undergoing AF-ablation procedure will be enrolled. The patients can arrive already taking rivaroxaban or, if they are naïve, the investigators will start the therapy and taking rivaroxaban for at least 4 weeks. The decision to prescribe rivaroxaban is under discretion of the treating physician, including the dose and duration of therapy.

Brief summary: The aim of IRIS study is to observe the safety and efficacy of Rivaroxaban in subjects undergoing catheter ablation for atrial fibrillation (AF) in real-world clinical practice.

The transcatheter ablation of AF is now considered an essential therapeutic strategy in the management of patients with this arrhythmia. In fact, it is known how fibrillating patients have a greater risk to develop thromboembolic phenomena; this risk can also increase during ablation (risk intrinsically with the procedure), therefore a careful anti-coagulant therapy is fundamental to avoid the formation of new thrombus and their dissemination through blood circulation.

The use of direct oral anti-coagulants (DOAC) in the fibrillating patient has been revealed a more safe and effective approach if compared with the standard therapy (direct vitamin K antagonists, VKA).

In the specific case of the Rivaroxaban, several experimental trials have shown how the uninterrupted administration of the drug before the ablation procedure is safe and valid. However, little information related to its use in the daily clinical assistance activity is still known and no real-life data are available for the Italian context.

Moreover, in Italy the uninterrupted strategy is not commonly used, and physicians often adopt the short interruption strategy.

Thus, the IRIS registry is aimed to collect new real-life data by collecting not only information regarding the effectiveness and safety of the drug, but also regarding the type of strategy (short interruption or uninterrupted strategy) used by the Italian centers participating to this study.

Detailed description: IRIS study is an Italian, multicenter, prospective and non-interventional study aimed to observe the safety and efficacy of uninterrupted or shortly interrupted catheter ablation procedure with Rivaroxaban in nonvalvular atrial fibrillation (NVAF) patients in real-world clinical practice.

250 patients treated with rivaroxaban undergoing AF-ablation procedure are expected to be enrolled in two years. The patients can arrive already taking rivaroxaban or if they are naïve, the investigators will start the therapy and taking rivaroxaban for at least 4 weeks. The decision to prescribe rivaroxaban is under discretion of the treating physician, including the dose and duration of therapy. Also the decision on the ablation technique and energy used during the procedure (radiofrequency catheter ablation or Cryoballoon Ablation) is up to the investigators.

Because this study is intended to assess the use of rivaroxaban in routine real-world clinical practice, study protocol will not interfere with the clinical management of patients or with the prescribing behaviors of attending physicians.

IRIS study will include all consenting patients and collect data at the following time points:

* One inclusion/exclusion visit at the hospital (during hospitalization or outpatient visit);
* Ablation procedure in hospital;
* One-month follow-up visit.

Baseline Data

The Following information will be collected for each enrolled patient at the initial visit:

* Patient demographics (date of birth, gender, ethnic origin, height/weight)
* Previous therapies or interventions to treat AF, including cardioversion and ablation
* AF characteristics (paroxysmal or persistent)
* Cardiovascular risk factors, concomitant cardiovascular diseases and other diseases/conditions
* Concomitant medications
* Stroke and bleeding risk profiles based on CHA2DS2 (Congestive heart failure, Hypertension, Age, Diabetes Mellitus, Stroke) - VASc27 (Vascular disease, Age, Sex) score, and HAS (Hypertension, Abnormal renal and liver function, Stroke) - BLED28 (Bleeding, Labile International Normalized Ratio, Elderly, Drugs or alcohol) score.
* Data on the AF-related diagnostic assessment, including electrocardiographic assessment, blood biochemistry, echocardiography and other diagnostic procedures, if performed as part of routine care
* Inform consent signature

Ablation procedure

* Type of Ablation procedure
* Activated Clotting Time (ACT)
* Adverse Event (AE)/Serious Adverse Event (SAE)
* Major complication events

Follow-Up Data Follow-up data at 1 month will be collected for all patients.

The following information will be obtained by phone or during a visit to the center for each enrolled patient:

* Any bleedings event described in the study protocol;
* Major complications described in the study protocol;
* Adherence to Non-VKA Oral Anticoagulant (NOACs) therapy,
* Concomitant medications;
* Concomitant procedures;
* AE/SAE.

Eligibility criteria: Inclusion Criteria:

* Suitable for anticoagulant therapy and catheter ablation;
* Scheduled for Non Valvular Atrial Fibrillation (NVAF) catheter ablation;
* Paroxysmal or persistent NVAF;
* Patient naïve or in therapy with Rivaroxaban;
* Written informed consent.

Exclusion Criteria:

* Patients who do not agree with study inclusion;
* Impossible to Non-VKA Oral Anticoagulant (NOAC);
* Moderate to severe hepatic impairment;
* Pregnancy or lactation;
* Creatinine Clearance (CrCl) \< 15 ml/min.

Primary outcomes:
measure: Incidence of thromboembolic and bleeding events.
timeFrame: 30 ± 5 days after the catheter ablation procedure.
Secondary outcomes:
measure: Effectiveness endpoints
timeFrame: 30 days after the catheter ablation procedure.
measure: Ablation procedure endpoints
timeFrame: 30 days after the catheter ablation procedure.
Other outcomes:
measure: Activated Clotting Time (ACT)
timeFrame: During the ablation procedure.
measure: Study medication adherence
timeFrame: At baseline and after 30 days.
Locations:
city: Roma
country: Italy
facility: Azienda Ospedaliero-Universitaria Policlinico Umberto I - Dipartimento di Scienze Cardiovascolari, Respiratorie, Nefrologiche, Anestesiologiche e Geriatriche.
Study officials:
affiliation: Policlinico Umberto I
name: Carlo Lavalle, Dr
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lakkireddy D, Reddy YM, Di Biase L, Vallakati A, Mansour MC, Santangeli P, Gangireddy S, Swarup V, Chalhoub F, Atkins D, Bommana S, Verma A, Sanchez JE, Burkhardt JD, Barrett CD, Baheiry S, Ruskin J, Reddy V, Natale A. Feasibility and safety of uninterrupted rivaroxaban for periprocedural anticoagulation in patients undergoing radiofrequency ablation for atrial fibrillation: results from a multicenter prospective registry. J Am Coll Cardiol. 2014 Mar 18;63(10):982-8. doi: 10.1016/j.jacc.2013.11.039. Epub 2014 Jan 8.
citation: January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC Jr, Conti JB, Ellinor PT, Ezekowitz MD, Field ME, Murray KT, Sacco RL, Stevenson WG, Tchou PJ, Tracy CM, Yancy CW; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2014 Dec 2;64(21):e1-76. doi: 10.1016/j.jacc.2014.03.022. Epub 2014 Mar 28. No abstract available.
citation: Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, Castella M, Diener HC, Heidbuchel H, Hendriks J, Hindricks G, Manolis AS, Oldgren J, Popescu BA, Schotten U, Van Putte B, Vardas P; ESC Scientific Document Group. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2016 Oct 7;37(38):2893-2962. doi: 10.1093/eurheartj/ehw210. Epub 2016 Aug 27. No abstract available.
citation: Calkins H, Hindricks G, Cappato R, Kim YH, Saad EB, Aguinaga L, Akar JG, Badhwar V, Brugada J, Camm J, Chen PS, Chen SA, Chung MK, Nielsen JC, Curtis AB, Davies DW, Day JD, d'Avila A, de Groot NMSN, Di Biase L, Duytschaever M, Edgerton JR, Ellenbogen KA, Ellinor PT, Ernst S, Fenelon G, Gerstenfeld EP, Haines DE, Haissaguerre M, Helm RH, Hylek E, Jackman WM, Jalife J, Kalman JM, Kautzner J, Kottkamp H, Kuck KH, Kumagai K, Lee R, Lewalter T, Lindsay BD, Macle L, Mansour M, Marchlinski FE, Michaud GF, Nakagawa H, Natale A, Nattel S, Okumura K, Packer D, Pokushalov E, Reynolds MR, Sanders P, Scanavacca M, Schilling R, Tondo C, Tsao HM, Verma A, Wilber DJ, Yamane T. 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation. Heart Rhythm. 2017 Oct;14(10):e275-e444. doi: 10.1016/j.hrthm.2017.05.012. Epub 2017 May 12. No abstract available.
citation: Nairooz R, Sardar P, Pino M, Aronow WS, Sewani A, Mukherjee D, Paydak H, Maskoun W. Meta-analysis of risk of stroke and thrombo-embolism with rivaroxaban versus vitamin K antagonists in ablation and cardioversion of atrial fibrillation. Int J Cardiol. 2015;187:345-53. doi: 10.1016/j.ijcard.2015.03.323. Epub 2015 Mar 21.
citation: Zhao Y, Yang Y, Tang X, Yu X, Zhang L, Xiao H. New oral anticoagulants compared to warfarin for perioperative anticoagulation in patients undergoing atrial fibrillation catheter ablation: a meta-analysis of continuous or interrupted new oral anticoagulants during ablation compared to interrupted or continuous warfarin. J Interv Card Electrophysiol. 2017 Apr;48(3):267-282. doi: 10.1007/s10840-016-0221-7. Epub 2017 Jan 12.
citation: Romero J, Cerrud-Rodriguez RC, Diaz JC, Michaud GF, Taveras J, Alviz I, Grupposo V, Cerna L, Avendano R, Kumar S, Kirchhof P, Natale A, Di Biase L. Uninterrupted direct oral anticoagulants vs. uninterrupted vitamin K antagonists during catheter ablation of non-valvular atrial fibrillation: a systematic review and meta-analysis of randomized controlled trials. Europace. 2018 Oct 1;20(10):1612-1620. doi: 10.1093/europace/euy133.
citation: Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, Breithardt G, Halperin JL, Hankey GJ, Piccini JP, Becker RC, Nessel CC, Paolini JF, Berkowitz SD, Fox KA, Califf RM; ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011 Sep 8;365(10):883-91. doi: 10.1056/NEJMoa1009638. Epub 2011 Aug 10.
citation: Piccini JP, Stevens SR, Lokhnygina Y, Patel MR, Halperin JL, Singer DE, Hankey GJ, Hacke W, Becker RC, Nessel CC, Mahaffey KW, Fox KA, Califf RM, Breithardt G; ROCKET AF Steering Committee & Investigators. Outcomes after cardioversion and atrial fibrillation ablation in patients treated with rivaroxaban and warfarin in the ROCKET AF trial. J Am Coll Cardiol. 2013 May 14;61(19):1998-2006. doi: 10.1016/j.jacc.2013.02.025. Epub 2013 Mar 14.
citation: Tao S, Otomo K, Ono Y, Osaka Y, Hirao T, Koura K, Manno T, Ueshima D, Shimizu S, Isobe M, Hirao K. Efficacy and safety of uninterrupted rivaroxaban taken preoperatively for radiofrequency catheter ablation of atrial fibrillation compared to uninterrupted warfarin. J Interv Card Electrophysiol. 2017 Mar;48(2):167-175. doi: 10.1007/s10840-016-0214-6. Epub 2016 Dec 9.
citation: Dillier R, Ammar S, Hessling G, Kaess B, Pavaci H, Buiatti A, Semmler V, Kathan S, Hofmann M, Lennerz C, Kolb C, Reents T, Deisenhofer I. Safety of continuous periprocedural rivaroxaban for patients undergoing left atrial catheter ablation procedures. Circ Arrhythm Electrophysiol. 2014 Aug;7(4):576-82. doi: 10.1161/CIRCEP.114.001586. Epub 2014 Jun 26.
citation: Cappato R, Marchlinski FE, Hohnloser SH, Naccarelli GV, Xiang J, Wilber DJ, Ma CS, Hess S, Wells DS, Juang G, Vijgen J, Hugl BJ, Balasubramaniam R, De Chillou C, Davies DW, Fields LE, Natale A; VENTURE-AF Investigators. Uninterrupted rivaroxaban vs. uninterrupted vitamin K antagonists for catheter ablation in non-valvular atrial fibrillation. Eur Heart J. 2015 Jul 21;36(28):1805-11. doi: 10.1093/eurheartj/ehv177. Epub 2015 May 14.
citation: Aryal MR, Ukaigwe A, Pandit A, Karmacharya P, Pradhan R, Mainali NR, Pathak R, Jalota L, Bhandari Y, Donato A. Meta-analysis of efficacy and safety of rivaroxaban compared with warfarin or dabigatran in patients undergoing catheter ablation for atrial fibrillation. Am J Cardiol. 2014 Aug 15;114(4):577-82. doi: 10.1016/j.amjcard.2014.05.038. Epub 2014 Jun 6.
citation: Li W, Gao C, Li M, Wang X, Qi D, Zhang Y, Hao P, Liu J, Zhu L. Safety and efficacy of rivaroxaban versus warfarin in patients undergoing catheter ablation of atrial fibrillation: a meta-analysis of observational studies. Discov Med. 2015 Mar;19(104):193-201.
citation: Phan K, Wang N, Pison L, Kumar N, Hitos K, Thomas SP. Rivaroxaban versus warfarin or dabigatran in patients undergoing catheter ablation for atrial fibrillation: A meta-analysis. Int J Cardiol. 2015 Apr 15;185:209-13. doi: 10.1016/j.ijcard.2015.03.102. Epub 2015 Mar 10. No abstract available.
citation: Camm AJ, Amarenco P, Haas S, Hess S, Kirchhof P, Kuhls S, van Eickels M, Turpie AG; XANTUS Investigators. XANTUS: a real-world, prospective, observational study of patients treated with rivaroxaban for stroke prevention in atrial fibrillation. Eur Heart J. 2016 Apr 7;37(14):1145-53. doi: 10.1093/eurheartj/ehv466. Epub 2015 Sep 1.
citation: Hecker J, Marten S, Keller L, Helmert S, Michalski F, Werth S, Sahin K, Tittl L, Beyer-Westendorf J. Effectiveness and safety of rivaroxaban therapy in daily-care patients with atrial fibrillation. Results from the Dresden NOAC Registry. Thromb Haemost. 2016 May 2;115(5):939-49. doi: 10.1160/TH15-10-0840. Epub 2016 Jan 21.
citation: Tamayo S, Frank Peacock W, Patel M, Sicignano N, Hopf KP, Fields LE, Sarich T, Wu S, Yannicelli D, Yuan Z. Characterizing major bleeding in patients with nonvalvular atrial fibrillation: a pharmacovigilance study of 27 467 patients taking rivaroxaban. Clin Cardiol. 2015 Feb;38(2):63-8. doi: 10.1002/clc.22373. Epub 2015 Jan 14.
citation: Coleman CI, Antz M, Bowrin K, Evers T, Simard EP, Bonnemeier H, Cappato R. Real-world evidence of stroke prevention in patients with nonvalvular atrial fibrillation in the United States: the REVISIT-US study. Curr Med Res Opin. 2016 Dec;32(12):2047-2053. doi: 10.1080/03007995.2016.1237937. Epub 2016 Sep 20.
citation: Camm AJ, Turpie AGG, Hess S, Amarenco P, Lambelet M, Haas S, van Eickels M, Kirchhof P; XANTUS Investigators. Outcomes after catheter ablation and cardioversion in patients with non-valvular atrial fibrillation: results from the prospective, observational XANTUS study. Europace. 2018 Jun 1;20(6):e87-e95. doi: 10.1093/europace/eux127.
citation: Sugrue A, Siontis KC, Piccini JP, Noseworthy PA. Periprocedural Anticoagulation Management for Atrial Fibrillation Ablation: Current Knowledge and Future Directions. Curr Treat Options Cardiovasc Med. 2018 Jan 25;20(1):3. doi: 10.1007/s11936-018-0600-8.
citation: Sawhney V, Shaukat M, Volkova E, Jones N, Providencia R, Honarbakhsh S, Dhillon G, Chow A, Lowe M, Lambiase PD, Dhinoja M, Sporton S, Earley MJ, Schilling RJ, Hunter RJ. Catheter ablation for atrial fibrillation on uninterrupted direct oral anticoagulants: A safe approach. Pacing Clin Electrophysiol. 2018 May 16. doi: 10.1111/pace.13370. Online ahead of print.
citation: Yoshimura A, Iriki Y, Ichiki H, Oketani N, Okui H, Maenosono R, Namino F, Miyata M, Ohishi M. Evaluation of safety and efficacy of periprocedural use of rivaroxaban and apixaban in catheter ablation for atrial fibrillation. J Cardiol. 2017 Jan;69(1):228-235. doi: 10.1016/j.jjcc.2016.03.014. Epub 2016 Apr 27.
citation: Schulman S, Kearon C; Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005 Apr;3(4):692-4. doi: 10.1111/j.1538-7836.2005.01204.x.
citation: Cappato R, Calkins H, Chen SA, Davies W, Iesaka Y, Kalman J, Kim YH, Klein G, Natale A, Packer D, Skanes A, Ambrogi F, Biganzoli E. Updated worldwide survey on the methods, efficacy, and safety of catheter ablation for human atrial fibrillation. Circ Arrhythm Electrophysiol. 2010 Feb;3(1):32-8. doi: 10.1161/CIRCEP.109.859116. Epub 2009 Dec 7.
citation: Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Chest. 2010 Feb;137(2):263-72. doi: 10.1378/chest.09-1584. Epub 2009 Sep 17.
citation: Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJ, Lip GY. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest. 2010 Nov;138(5):1093-100. doi: 10.1378/chest.10-0134. Epub 2010 Mar 18.
citation: Fleiss JL, Levin B, Paik MC. Statistical methods for rates and proportions (3rd edn). Wiley, New Jersey, 2003.
citation: Newcombe RG. Two-sided confidence intervals for the single proportion: comparison of seven methods. Stat Med. 1998 Apr 30;17(8):857-72. doi: 10.1002/(sici)1097-0258(19980430)17:83.0.co;2-e.
citation: Velu S, Pathiraja J, Barr C, Forsey P, Lapper A, Kidd G, Arya A, Petkar S. A wide range of catheter ablations can be safely performed without interrupting novel oral anticoagulants (NOAC's). EP Europace, Volume 19, Issue suppl_3, 1 June 2017, Page iii298