Clinical trial NCT03182218: Periprocedural Direct Oral Anticoagulant Management
Official title: Prospective Observational Study of the Direct Oral Anticoagulants Periprocedural Management
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Periprocedural Complication
Keywords: Periprocedural
Anticoagulation
Dabigatran
Rivaroxaban
Apixaban
Edoxaban
Direct oral anticoagulant
Surgery
Anaesthesia
Novel oral anticoagulant
Perioperative medicine
Lead sponsor: Fundación para la Investigación del Hospital Clínico de Valencia
Sponsor class: OTHER
First posted: 2017-06-09
Enrollment: 1100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult patient under treatment with direct oral anticoagulant who requires a surgery or an invasive procedural, both scheduled or urgent.

Brief 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.

Detailed 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.

Eligibility criteria: 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:

* None

Primary outcomes:
measure: Periprocedural thrombotic complications
timeFrame: 1 month
measure: Periprocedural hemorrhagic complications
timeFrame: 1 month
Secondary outcomes:
measure: Outcome of bridging therapy
timeFrame: Between one week before and one month after procedural
measure: Knowing actual DOAC management in clinical practice
timeFrame: Between one week before and one month after procedural
Other outcomes:
Locations:
city: Mataró
country: Spain
facility: Hospital de Mataró
state: Barcelona
city: Sabadell
country: Spain
facility: Hospital de Sabadell-Parc Taulí
state: Barcelona
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
state: Cantabria
city: Leganés
country: Spain
facility: Hospital Universitario Severo Ochoa
state: Madrid
city: La Laguna
country: Spain
facility: Hospital Universitario de Canarias
state: Tenerife
city: Manises
country: Spain
facility: Hospital de Manises
state: Valencia
city: Alzira
country: Spain
facility: Hospital Universitario La Ribera
city: Barcelona
country: Spain
facility: Parc Salut Mar
city: Barcelona
country: Spain
facility: Fundació Puigvert
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Cadiz
country: Spain
facility: Hospital Puerta del Mar
city: Galdakao
country: Spain
facility: Hospital de Galdakao-Usánsolo
city: Getafe
country: Spain
facility: Hospital Universitario de Getafe
city: Las Palmas de Gran Canaria
country: Spain
facility: Hospital Universitario de Gran Canaria Doctor Negrín
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Universitario Infanta Leonor
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Malaga
country: Spain
facility: Hospital Virgen de la Victoria
city: Marbella
country: Spain
facility: Hospital Costa del Sol
city: Móstoles
country: Spain
facility: Hospital Universitario de Móstoles
city: Pamplona
country: Spain
facility: Clínica Universidad de Navarra
city: Segovia
country: Spain
facility: Hospital General de Segovia
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: Toledo
country: Spain
facility: Hospital Virgen de la Salud
city: Valencia
country: Spain
facility: Hospital Clínico Universitario
city: Valencia
country: Spain
facility: Consorcio H. General Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital Universitari i Politècnic La Fe
city: Valencia
country: Spain
facility: Hospital Dr Peset
city: Xàtiva
country: Spain
facility: Hospital Lluís Alcanyís
city: Zaragoza
country: Spain
facility: Hospital Miguel Servet
Study officials:
affiliation: Fundación para la Investigación del Hospital Clínico de Valencia
name: Raquel Ferrandis Comes, Doctor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Perez-Villacastin J, Perez 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.
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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.
citation: Llau JV, Ferrandis R, Castillo J, de Andres J, Gomar C, Gomez-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. Spanish.
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.
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.
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.
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. doi: 10.1161/CIRCULATIONAHA.112.135681. No abstract available.
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. No abstract available.
citation: Ferrandis R, Castillo J, de Andres J, Gomar C, Gomez-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.