Observatory of Invasive Procedures and Bleeding in Patients Treated With New Oral Anticoagulants (GIHP-NACO)

September 28, 2021 updated by: University Hospital, Grenoble

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The management of critical situations is difficult for several reasons:

  • First, there is significant intra- and inter-individual variability in the pharmacokinetics of NOACs, which is further heightened in the critical setting by drug interactions with other agents that interfere with P-GLYCOPROTEIN (P-GP) and cytochrome ( cytochrome P4503A4) in patients who are often elderly and multi medicated, and by rapid variations in renal function, which is essential for elimination of NOACs.
  • Second, biological guidance is weak: there is no clearcut therapeutic range nor any validated hemostatic safety cutoff, as is the case with the International Normalized Ratio (INR) for VKAs. Conventional coagulation tests (PT/aPTT) are poorly standardized and difficult to interpret. Assays to measure the serum concentrations of these drugs are not widespread outside of a few teaching hospitals.
  • Third, there is a lack of clinical experience. Analyses of critical situations that occurred during clinical trials were done after the fact and the data collected are heterogeneous and incomplete. Clinical cases reported in the literature are rarely well documented.

The objective of the observatory is to rapidly acquire documented and thorough feedback on clinical experience with these new drugs that will be able to confer a higher level of evidence to the management recommendations for treated patients.

Study Type

Observational

Enrollment (Actual)

1166

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Brussels, Belgium
        • CHU Brugmann
  • France
      • Agen, France
        • CH Agen
      • Amiens, France
        • CHU d'AMIENS
      • Annecy, France
        • CHR Annecy
      • Besançon, France
        • CHU Besançon
      • Bordeaux, France
        • CHU Bordeaux
      • Castres, France
        • Ch Castres
      • Chambery, France
        • CH Chambery
      • Clermont-ferrand, France
        • CHU Clermont-Ferrand
      • Contamine-sur-Arve, France
        • CH Alpes Leman
      • Dijon, France
        • CHU Dijon
      • GAP, France
        • CH Gap
      • Grenoble, France, 38043
        • CHU de Grenoble
      • Grenoble, France
        • Groupe Hospitalier Mutualiste Grenoble
      • Lille, France
        • CHRU Lille
      • Lyon, France
        • HCL - Edouard Herriot
      • Lyon, France
        • HCL - Hôpital de la Croix-Rousse
      • Lyon, France
        • HCL - Lyon Sud
      • Marseille, France
        • CHU Marseille
      • Montpellier, France
        • CHU Montpellier
      • Nancy, France
        • CHU Nancy
      • Nancy, France
        • Centre Emile Gallé - SINCAL
      • Nantes, France
        • CHU Nantes
      • Nimes, France
        • CHU Nîmes
      • Niort, France
        • CH de Niort
      • Paris, France
        • APHP - Antoine Béclère
      • Paris, France
        • APHP - Tenon
      • Paris, France
        • APHP Henri Mondor
      • Paris, France
        • APHP Hôpital Bichat
      • Paris, France
        • APHP Hôpital Cochin
      • Paris, France
        • APHP Site St Antoine
      • Paris, France
        • Aphp-Hegp
      • Paris, France
        • APHP-Hôpital Beaujon
      • Paris, France
        • Centre Hôpital Américain
      • Paris, France
        • CHU Bicêtre
      • Rennes, France
        • Chu Rennes
      • Strasbourg, France
        • CHRU Strasbourg - Hôpital Civil
      • Toulon, France
        • Hôpital d'instruction des armées Sainte-Anne
      • Toulouse, France
        • CHU Toulouse
      • Voiron, France
        • CH Voiron
    • haute-Savoie
      • Thonon-les-Bains, haute-Savoie, France
        • Hopitaux du Leman

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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)

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • Pregnant women
  • Refusal to participate in the study: listed in the non-inclusion registry
  • Antithrombotics indicated for the prevention of venous thromboembolism

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
complications and compliance with GIHP recommendations
Description at 1 month post-intervention of an potential event
Other: complications and compliance with GIHP recommendations
Description of complications, compliance, major bleeding events, treatments, reversal strategies.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
complications and compliance with GIHP recommendations
Time Frame: At 1 month

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
NOAC management
Time Frame: during the perioperative period
All NOAC treatments will be recorded
during the perioperative period
reversal strategies description
Time Frame: during the perioperative period
use or not of reversal strategies will be described
during the perioperative period
Coagulation test results
Time Frame: during the perioperative period
Coagulation test results will be recorded
during the perioperative period

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Grenoble

Collaborators

Floralis

Investigators

  • Principal Investigator: Pierre ALBALADEJO, MD, University Hospital, Grenoble

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2013

Primary Completion (Actual)

March 1, 2016

Study Completion (Actual)

December 1, 2016

Study Registration Dates

First Submitted

July 3, 2014

First Submitted That Met QC Criteria

July 3, 2014

First Posted (Estimate)

July 9, 2014

Study Record Updates

Last Update Posted (Actual)

October 6, 2021

Last Update Submitted That Met QC Criteria

September 28, 2021

Last Verified

January 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DCIC 13 18

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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