Periprocedural Direct Oral Anticoagulant Management

Periprocedural Complication Clinical Trial

— RA-ACOD  

Official title:

Prospective Observational Study of the Direct Oral Anticoagulants Periprocedural Management

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03182218
• Other study ID #: INC-ACO-2013-01
• Status: Completed
• Start date: February 2015
• Est. completion date: June 2018

Study information

• Verified date: August 2018
• Source: Fundación para la Investigación del Hospital Clínico de Valencia
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Direct oral anticoagulants (DOAC) are a new drug group that has been approved for chronic anticoagulation of patients in atrial fibrillation or suffering acute thrombosis, between others. The need of surgery of a patient in atrial fibrillation is round 10% per year.

Due to DOAC short time of commercialization and the lack of experience, the proper management of DOAC when a patient in this treatment needs a scheduled or urgent procedure, has not yet been established. This fact may mean both the decrease of the anticoagulant treatment efficacy and the increase of the haemorrhage complications in the perioperative period.

With the aim of gaining additional information about this aspect, a multicentre, prospective and observational study (classified by the spanish drug society, AEMPS, as non-interventional trial, EPA-SP) about the DOAC management, before a scheduled or urgent surgery, in normal clinical practice, is proposed.

Description:

When an anticoagulated patient is scheduled for surgery or an invasive procedure, the physician's worry is how to achieve needing an optimal haemostasis without increasing the risk of thrombosis. For decades, the main drug for chronic anticoagulation has been antivitamin-k (warfarin or acenocoumarol). In the majority of patients, the periprocedural management proposal has been stopping the drug and giving a short acting anticoagulant for some days before surgery, known as bridging therapy strategy, mostly done with a low-molecular weight heparin (LMWH).

The debate about the best perioperative management of the anticoagulated patients has increased with the arrival on the market of direct oral anticoagulants (DOAC), by the moment approved for long-term anticoagulation in patients with atrial fibrillation and for the treatment of pulmonary embolism. DOAC could be classified in two groups: direct inhibitors of thrombin (the only current available drug is dabigatran) and direct inhibitors of factor Xa (rivaroxaban, apixaban, edoxaban, and others soon to come). DOAC have pharmacokinetic characteristics that seem to favour stopping the drug for some days without substitution in the vast majority of the patients. Nevertheless, current lack of experience in the management of high doses of DOAC during the perioperative period, the absence of effective antagonists to reverse the anticoagulation, the unsuitable standardized laboratory monitoring and, also, the different pharmacokinetics between patients receiving these drugs, have made challenging to standardize the optimal management in the perioperative period. Some proposals have been published in last years from expert consensus, based on pharmacokinetic data, but DOAC short time of commercialization and the difficulties to interpret the post-hoc analysis from the randomized trials, for the heterogeneity of the included population and the wide kind of surgeries, most of them with low bleeding risk, have moved the spanish working group on perioperative management of haemostasis to plan a multi-institutional registry to gain experience and information in the periprocedural (urgent or scheduled) management of DOAC.

The authors designed an observational, prospective, multicentre study including patients under long-term DOAC treatment for atrial fibrillation or treatment of venous thromboembolism who are scheduled or need an urgent procedure. Data collected were demographic, related with the DOAC management and with the possible haemorrhagic or thrombotic events with a follow-up of 30 day. A univariable analysis and a multivariate regression model were applied using all the available co-variables. Bilateral hypothesis contrast were considered significant if α < 0.05.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1100
• Est. completion date: June 2018
• Est. primary completion date: February 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients 18 years of age and older

• Under direct oral anticoagulant

• Urgent or scheduled surgery or invasive procedure needed

• Signed and dated informed consent form

Exclusion Criteria:

Related Conditions & MeSH terms

• Periprocedural Complication

Intervention

Drug:
• Direct oral anticoagulant
Time of direct oral anticoagulant withdrawal Use or not of bridging with low molecular weight heparin

Locations

Country	Name	City	State
Spain	Hospital Universitario La Ribera	Alzira
Spain	Fundació Puigvert	Barcelona
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Parc Salut Mar	Barcelona
Spain	Hospital Puerta del Mar	Cadiz
Spain	Hospital de Galdakao-Usánsolo	Galdakao
Spain	Hospital Universitario de Getafe	Getafe
Spain	Hospital Universitario de Canarias	La Laguna	Tenerife
Spain	Hospital Universitario de Gran Canaria Doctor Negrín	Las Palmas de Gran Canaria
Spain	Hospital Universitario Severo Ochoa	Leganés	Madrid
Spain	Hospital General Universitario Gregorio Marañón	Madrid
Spain	Hospital Universitario Infanta Leonor	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Virgen de la Victoria	Malaga
Spain	Hospital de Manises	Manises	Valencia
Spain	Hospital Costa del Sol	Marbella
Spain	Hospital de Mataró	Mataró	Barcelona
Spain	Hospital Universitario de Móstoles	Móstoles
Spain	Clínica Universidad de Navarra	Pamplona
Spain	Hospital de Sabadell-Parc Taulí	Sabadell	Barcelona
Spain	Hospital Universitario Marques de Valdecilla	Santander	Cantabria
Spain	Hospital General de Segovia	Segovia
Spain	Hospital Universitario Virgen del Rocío	Sevilla
Spain	Hospital Virgen de la Salud	Toledo
Spain	Consorcio H. General Universitario de Valencia	Valencia
Spain	Hospital Clínico Universitario	Valencia
Spain	Hospital Dr Peset	Valencia
Spain	Hospital Universitari i Politècnic La Fe	Valencia
Spain	Hospital Lluís Alcanyís	Xàtiva
Spain	Hospital Miguel Servet	Zaragoza

Sponsors (1)

Lead Sponsor	Collaborator
Fundación para la Investigación del Hospital Clínico de Valencia

Country where clinical trial is conducted

Spain, 

References & Publications (13)

Barrios V, Calderón A, Escobar C, de la Figuera M; Primary Care Group in the Clinical Cardiology Section of the Spanish Society of Cardiology. Patients with atrial fibrillation in a primary care setting: Val-FAAP study. Rev Esp Cardiol (Engl Ed). 2012 Jan;65(1):47-53. doi: 10.1016/j.recesp.2011.08.008. Epub 2011 Nov 4. English, Spanish. Erratum in: Rev Esp Cardiol (Engl). 2012 May;65(5):494. — View Citation

Cea-Calvo L, Redón J, Martí-Canales JC, Lozano JV, Llisterri JL, Fernández-Pérez C, Aznar J, González-Esteban J. [Prevalence of low glomerular filtration rate in the elderly population of Spain. The PREV-ICTUS study]. Med Clin (Barc). 2007 Nov 17;129(18):681-7. Spanish. — View Citation

Ferrandis R, Castillo J, de Andrés J, Gomar C, Gómez-Luque A, Hidalgo F, Llau JV, Sierra P, Torres LM. The perioperative management of new direct oral anticoagulants: a question without answers. Thromb Haemost. 2013 Sep;110(3):515-22. doi: 10.1160/TH12-11-0868. Epub 2013 Jul 11. Review. — View Citation

Gallego P, Apostolakis S, Lip GY. Bridging evidence-based practice and practice-based evidence in periprocedural anticoagulation. Circulation. 2012 Sep 25;126(13):1573-6. — View Citation

Llau JV, Ferrandis R, Castillo J, de Andrés J, Gomar C, Gómez-Luque A, Hidalgo F, Torres LM. [Recommendations on use of direct oral anticoagulants in the perioperative period]. Med Clin (Barc). 2012 Oct;139 Suppl 2:46-50. doi: 10.1016/S0025-7753(12)70042-8. Review. Spanish. — View Citation

Llau JV, Ferrandis R. Letter by Llau and Ferrandis regarding article, "Bridging evidence-based practice and practice-based evidence in periprocedural anticoagulation". Circulation. 2013 May 14;127(19):e616. doi: 10.1161/CIRCULATIONAHA.112.151506. — View Citation

Mavrakanas T, Bounameaux H. The potential role of new oral anticoagulants in the prevention and treatment of thromboembolism. Pharmacol Ther. 2011 Apr;130(1):46-58. doi: 10.1016/j.pharmthera.2010.12.007. Epub 2010 Dec 24. Review. — View Citation

Pérez-Villacastín J, Pérez Castellano N, Moreno Planas J. Epidemiology of atrial fibrillation in Spain in the past 20 years. Rev Esp Cardiol (Engl Ed). 2013 Jul;66(7):561-5. doi: 10.1016/j.rec.2013.02.012. Epub 2013 May 28. Review. — View Citation

Schulman S, Crowther MA. How I treat with anticoagulants in 2012: new and old anticoagulants, and when and how to switch. Blood. 2012 Mar 29;119(13):3016-23. doi: 10.1182/blood-2011-10-378950. Epub 2012 Feb 1. Review. — View Citation

Turpie AG, Kreutz R, Llau J, Norrving B, Haas S. Management consensus guidance for the use of rivaroxaban--an oral, direct factor Xa inhibitor. Thromb Haemost. 2012 Nov;108(5):876-86. doi: 10.1160/TH12-03-0209. Epub 2012 Sep 26. Review. — View Citation

van Ryn J, Stangier J, Haertter S, Liesenfeld KH, Wienen W, Feuring M, Clemens A. Dabigatran etexilate--a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity. Thromb Haemost. 2010 Jun;103(6):1116-27. doi: 10.1160/TH09-11-0758. Epub 2010 Mar 29. Review. — View Citation

Weitz JI, Eikelboom JW, Samama MM. New antithrombotic drugs: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e120S-e151S. doi: 10.1378/chest.11-2294. Review. — View Citation

Wittkowsky AK. Novel oral anticoagulants and their role in clinical practice. Pharmacotherapy. 2011 Dec;31(12):1175-91. doi: 10.1592/phco.31.12.1175. Review. — View Citation

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Periprocedural thrombotic complications	Accumulative incidence rate of thrombotic events (cardiovascular, neurological, or venous thromboembolic event)	1 month
Primary	Periprocedural hemorrhagic complications	Accumulative incidence rate of minor and major bleeding events	1 month
Secondary	Outcome of bridging therapy	Relationship between the incidence of complications and the use of bridging therapy.	Between one week before and one month after procedural
Secondary	Knowing actual DOAC management in clinical practice	Composite of time of withdrawal of direct oral anticoagulant, use or not of low molecular weight heparin as bridge therapy, time of reintroduction of direct oral anticoagulant	Between one week before and one month after procedural