Observatory of Invasive Procedures and Bleeding in Patients Treated With New Oral Anticoagulants

NCT02185027 | Completed

• 1 other identifier: DCIC 13 18
• Study Type: observational
• Target: 1,166
• Locations: 2 countries
• Sites: 41

Brief Summary

The arrival on the market of direct oral factor Xa and factor IIa inhibitors (dabigatran (Pradaxa®), rivaroxaban (Xarelto®), apixaban (Eliquis®) and others soon to come) raises novel questions among clinicians confronted with the emergency management of patients treated with these new drugs. It is likely that these new oral anticoagulants (NOACs) will eventually win a significant market share in the indications secondary prevention of venous thromboembolism and prevention of cardioembolic events in patients with nonvalvular atrial fibrillation, due to their net clinical benefit and their practicality of use compared with vitamin K antagonists (VKAs). However, despite the fact that NOACs reduce the incidence of intracranial bleeding by about half compared with VKAs, the risk remains significant; furthermore, in clinical trials, these drugs had little or no effect on reducing the incidence of major extracranial bleeding. In everyday practice, where the indication could be expanded to unselected populations and due to a potential for misuse, it is likely that the incidence of bleeding complications will be higher than that reported in clinical trials. Indeed, the numerous alerts emanating from regulatory agencies in various countries (US, Australia, etc.) bear witness to this, and should serve as a reminder that these anticoagulants have a real potential for bleeding complications and, in the absence of an antidote, there is no validated management strategy. Furthermore, as these drugs can be prescribed for months or years, patients may eventually be exposed to situations at high hemorrhagic risk, such as emergency surgery or invasive procedures, trauma, etc. Analysis of data from the trial : dabigatran versus warfarin in patients with atrial fibrillation (RE-LY) showed that during the two years of follow-up, approximately 25% of the patients underwent an invasive procedure, ranging from pacemaker insertion to major surgery. Thus, a large proportion of patients treated with NOACs are concerned by this issue. In anticipation of a gradually increasing influx of patients in a critical situation (active bleeding or need to rapidly secure hemostasis before an invasive procedure), it is urgent to define the conduct to adopt based on the experience gained from the earliest cases. This is the objective of the French-speaking GIHP-NACO observatory set up by the GIHP (French Working Group on Perioperative Hemostasis). For the moment, then, the management recommendations derive from expert opinions based on pharmacokinetic data and on the partial correction of NOAC-induced hypocoagulability by various nonspecific procoagulants (non-activated or activated prothrombin complex concentrates, recombinant factor VIIa). These procoagulants are currently used in an empirical manner to control bleeding, with as many successes as failures reported in the literature, and their benefit-risk ratio in these patients is therefore uncertain.

Conditions

Venous Thromboembolism; Atrial Fibrillation

Keywords

Oral anticoagulants; Surgery; Haemorrhage; Emergency

Outcome Measures

Primary Outcomes (1)

• complications and compliance with GIHP recommendations

  Association between the incidence rate at 1 month post-intervention of an event among the following complications and compliance with GIHP recommendations (appended) evaluated by a composite endpoint Major cardiovascular event ( acute coronary syndrome, cardiogenic shock, stroke or Transient Ischemic Attack (TIA), Central Nervous System (extra-CNS) thromboembolic event). Major bleeding event in the group of patients who had an emergency invasive procedure. Continued bleeding after management (treatment, reversal) in the group of patients managed for bleeding. Compliance with GIHP recommendations (appended) evaluated by a composite endpoint based on: * Observance of reversal strategies * Observance of the therapeutic window between the last administration and the procedure, in cases where the NOAC was stopped

  At 1 month

Secondary Outcomes (3)

• NOAC management

  during the perioperative period

• reversal strategies description

  during the perioperative period

• Coagulation test results

  during the perioperative period

Study Arms (1)

complications and compliance with GIHP recommendations

Description at 1 month post-intervention of an potential event

Other: complications and compliance with GIHP recommendations

Interventions

complications and compliance with GIHP recommendations OTHER

Description of complications, compliance, major bleeding events, treatments, reversal strategies.

complications and compliance with GIHP recommendations

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Subjects managed in view of surgery or an invasive procedure, emergency or not managed and hospitalized for active bleeding with a long-term therapy (in the indication atrial fibrillation or treatment of pulmonary embolism or deep vein thrombosis) by one antithrombotic agent (Dabigatran, Rivaroxaban, Apixaban)

You may qualify if:

• Age ≥ 18 years
• Managed in view of surgery or an invasive procedure, emergency or not
• Managed and hospitalized for active bleeding
• Long-term therapy (in the indication atrial fibrillation or treatment of pulmonary embolism or deep vein thrombosis) by at least one antithrombotic agent from the following list: DABIGATRAN ETEXILATE MESYLATE or RIVAROXABAN or APIXABAN

You may not qualify if:

• Pregnant women
• Antithrombotics indicated for the prevention of venous thromboembolism

Sponsors & Collaborators

• University Hospital, Grenoble: lead
• Floralis: collaborator

Study Sites (41)

CHU Brugmann

Brussels, Belgium

Location

Hôpitaux du Léman

Thonon-les-Bains, haute-Savoie, France

Location

CH Agen

Agen, France

Location

CHU d'Amiens

Amiens, France

Location

CHR Annecy

Annecy, France

Location

CHU Besançon

Besançon, France

Location

CHU Bordeaux

Bordeaux, France

Location

CH Castres

Castres, France

Location

CH Chambéry

Chambéry, France

Location

CHU Clermont-Ferrand

Clermont-Ferrand, France

Location

CH Alpes leman

Contamine-sur-Arve, France

Location

CHU Dijon

Dijon, France

Location

CH Gap

Gap, France

Location

CHU de Grenoble

Grenoble, 38043, France

Location

Groupe Hospitalier Mutualiste Grenoble

Grenoble, France

Location

CHRU Lille

Lille, France

Location

HCL - Edouard Herriot

Lyon, France

Location

HCL - Hôpital de la Croix-Rousse

Lyon, France

Location

HCL - Lyon Sud

Lyon, France

Location

CHU Marseille

Marseille, France

Location

CHU Montpellier

Montpellier, France

Location

Centre Emile Gallé - SINCAL

Nancy, France

Location

CHU Nancy

Nancy, France

Location

CHU Nantes

Nantes, France

Location

CH de Niort

Niort, France

Location

CHU Nimes

Nîmes, France

Location

APHP - Antoine Beclere

Paris, France

Location

APHP - Tenon

Paris, France

Location

APHP Henri Mondor

Paris, France

Location

APHP Hôpital Bichat

Paris, France

Location

APHP Hôpital Cochin

Paris, France

Location

APHP Site St Antoine

Paris, France

Location

Aphp-Hegp

Paris, France

Location

APHP-Hôpital Beaujon

Paris, France

Location

Centre Hôpital Américain

Paris, France

Location

CHU Bicêtre

Paris, France

Location

CHU Rennes

Rennes, France

Location

CHRU Strasbourg - Hôpital Civil

Strasbourg, France

Location

Hôpital d'Instruction des Armées Sainte-Anne

Toulon, France

Location

CHU Toulouse

Toulouse, France

Location

CH Voiron

Voiron, France

Location

Related Publications (6)

• Pernod G, Albaladejo P, Godier A, Samama CM, Susen S, Gruel Y, Blais N, Fontana P, Cohen A, Llau JV, Rosencher N, Schved JF, de Maistre E, Samama MM, Mismetti P, Sie P; Working Group on Perioperative Haemostasis. Management of major bleeding complications and emergency surgery in patients on long-term treatment with direct oral anticoagulants, thrombin or factor-Xa inhibitors: proposals of the working group on perioperative haemostasis (GIHP) - March 2013. Arch Cardiovasc Dis. 2013 Jun-Jul;106(6-7):382-93. doi: 10.1016/j.acvd.2013.04.009. Epub 2013 Jun 25.

  PMID: 23810130 BACKGROUND

• Marlu R, Hodaj E, Paris A, Albaladejo P, Cracowski JL, Pernod G. Effect of non-specific reversal agents on anticoagulant activity of dabigatran and rivaroxaban: a randomised crossover ex vivo study in healthy volunteers. Thromb Haemost. 2012 Aug;108(2):217-24. doi: 10.1160/TH12-03-0179. Epub 2012 May 25.

  PMID: 22627883 BACKGROUND

• Sie P, Samama CM, Godier A, Rosencher N, Steib A, Llau JV, Van der Linden P, Pernod G, Lecompte T, Gouin-Thibault I, Albaladejo P; Working Group on Perioperative Haemostasis; French Study Group on Thrombosis and Haemostasis. Surgery and invasive procedures in patients on long-term treatment with direct oral anticoagulants: thrombin or factor-Xa inhibitors. Recommendations of the Working Group on Perioperative Haemostasis and the French Study Group on Thrombosis and Haemostasis. Arch Cardiovasc Dis. 2011 Dec;104(12):669-76. doi: 10.1016/j.acvd.2011.09.001. Epub 2011 Oct 29.

  PMID: 22152517 BACKGROUND

• Healey JS, Eikelboom J, Douketis J, Wallentin L, Oldgren J, Yang S, Themeles E, Heidbuchel H, Avezum A, Reilly P, Connolly SJ, Yusuf S, Ezekowitz M; RE-LY Investigators. Periprocedural bleeding and thromboembolic events with dabigatran compared with warfarin: results from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) randomized trial. Circulation. 2012 Jul 17;126(3):343-8. doi: 10.1161/CIRCULATIONAHA.111.090464. Epub 2012 Jun 14.

  PMID: 22700854 BACKGROUND

• Heidbuchel H, Verhamme P, Alings M, Antz M, Hacke W, Oldgren J, Sinnaeve P, Camm AJ, Kirchhof P; European Heart Rhythm Association. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace. 2013 May;15(5):625-51. doi: 10.1093/europace/eut083.

  PMID: 23625942 BACKGROUND

• Godon A, Gabin M, Levy JH, Huet O, Chapalain X, David JS, Tacquard C, Sattler L, Minville V, Memier V, Blanie A, Godet T, Leone M, De Maistre E, Gruel Y, Roullet S, Vermorel C, Samama CM, Bosson JL, Albaladejo P; GIHP-NACO Study Group. Management of urgent invasive procedures in patients treated with direct oral anticoagulants: An observational registry analysis. Thromb Res. 2022 Aug;216:106-112. doi: 10.1016/j.thromres.2022.06.005. Epub 2022 Jun 22.

  PMID: 35785621 DERIVED

MeSH Terms

Conditions

Venous Thromboembolism; Atrial Fibrillation; Hemorrhage; Emergencies

Interventions

Compliance

Condition Hierarchy (Ancestors)

Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Heart Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes

Intervention Hierarchy (Ancestors)

Elasticity; Mechanical Phenomena; Physical Phenomena

Study Officials

• Pierre Albaladejo, MD

  University Hospital, Grenoble

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 3, 2014
• First Posted: July 9, 2014
• Study Start: June 1, 2013
• Primary Completion: March 1, 2016
• Study Completion: December 1, 2016
• Last Updated: October 6, 2021

Record last verified: 2018-01

Locations

BE (1); FR (40)