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Early Versus Late Resumption of Anticoagulation in Patients With Both High Thrombosis Risk and Major HEmoRrhage (RATHER)

9 mars 2016 mis à jour par: Centre Hospitalier Universitaire de Saint Etienne

Randomized Assay Evaluating the Risk/Benefit of Early Versus Late Resumption of Anticoagulation in Patients With Major, Non-trauma Related Hemorrhage Occurring While on Anticoagulant Treatment for a High Risk of Thrombosis.

In patients with a high thromboembolic risk, withdrawing anticoagulant treatment is recommended in some situations, including when major hæmorrhage occurs. But withdrawing treatment can be risky. In patients on a curative dose of anticoagulant medicine, treatment withdrawal heightens the risk of thromboembolic events occurring, with potentially major consequences. For instance, mechanical valve thrombosis is fatal in 15% of patients. Resumption of anticoagulation is therefore critical in patients at high risk for thromboembolic events.

However, in these patients having presented major hæmorrhage, resumption of anticoagulation heightens the risk of hæmorrhage recurrence. This risk is even higher when the original hæmorrhage was not accessible via surgical, endoscopic or endoluminal hemostasis.

As far as investigators know, there is no data in the literature to rely on when the major hæmorrhage is not accessible via hemostatic intervention and the risk of thrombosis is high. When confronted with patients who need anticoagulation but have a high risk of hæmorrhage recurrence, the question of when treatment should be resumed has not been resolved. This is why investigators propose to conduct a randomised comparative study to evaluate two treatment strategies - early resumption (H48 to H72) versus late resumption (H120 to H144) of anticoagulation.

MAIN OBJECTIVE: The main objective of the present study is to evaluate in terms of bleeding risk, thrombosis risk and mortality at one month, the effect of early vs. late resumption of anticoagulation in patients having presented with serious hæmorrhage while on curative-dose anticoagulants and facing a high thromboembolic risk.

Aperçu de l'étude

Statut

Résilié

Les conditions

Intervention / Traitement

Description détaillée

STUDY DESIGN: This is a comparative, randomised, open study assessing after 1 month and 3 months the effect of early (H48 to 72) versus late (H120 to 144) resumption of anticoagulation in patients presenting with serious bleeding while on anticoagulants (excluding intracerebral bleeding) and with a thromboembolic risk evaluated as high (except mitral prostheses). The accumulated frequency of major hæmorrhage, thromboembolic events and deaths should be 26% in case of early resumption and 15% in case of late resumption, i.e. a relative risk reduction of 43%. Based on this hypothesis, to obtain 80% power with two-sided α being 5%, each group should include 208 patients, for a total of 416 patients.

EVALUATION CRITERIA: The main criteria in this study will be the accumulated one-month incidence of hæmorrhage recurrence, thromboembolic complications and deaths. It is a combined criterion associating:

  • Fatal hæmorrhage proven by autopsy or sudden deaths in a clinical context strongly suggestive of hæmorrhage
  • Fatal thromboembolic events proven by autopsy or imagery or sudden deaths in a clinical context strongly suggestive of thrombosis
  • Any clinically significant hæmorrhage leading to temporary (> 24 hours) or permanent withdrawal of anticoagulant treatment
  • Any symptomatic thromboembolic event in any territory, proven by imagery or surgery

These events will be validated by a committee for the validation of critical events blind to the date of anticoagulant treatment resumption. The secondary evaluation criteria will be symptomatic hæmorrhages, fatal or not, symptomatic thromboembolic incidents, fatal or not, and mortality at 1 month and 3 mont

Type d'étude

Interventionnel

Inscription (Réel)

14

Phase

  • Phase 3

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

  • France
      • Saint-Etienne, France, 42055
        • Service d'Urgences et de Réanimation Medicale, CHU de Saint-Etienne
      • Saint-etienne, France, 42000
        • CHU de Saint-Etienne

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans à 90 ans (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

Inclusion Criteria:affiliated with or a beneficiary of a social security category

  • age > 18 years old
  • with major bleeding (ISTH) and highs thrombosis risk (ACCP 2008)
  • having signed the inform consent form

Exclusion Criteria:

  • intracranial bleeding
  • artificial heart valves
  • bleeding with hemostatic surgical
  • low and moderate thrombosis risk
  • INR>1.2
  • hemodynamic instability contra-indication to HBPM or HNF treatment
  • With previous history of HIT (heparin Inducted thrombopenia)
  • patient who need antiaggregant treatment before anticoagulant treatment
  • Hæmoglobin count < 8 g/dl or patients with hæmoglobin count < 10 g/dl combined with acute coronary syndrome or proven heart failure
  • pregnant
  • Polytraumatism
  • with curatif heparin before randomisation

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: UFH Early group
anticoagulant (UFH or LMWH) reintroduction at 48h to 72h after hemorrhage
Médicament: UFH Early group

Either curative dose, intravenous unfractionated heparin (UFH) so as to reach an anti-Xa activity between 0.3 and 0.7 IU/mL, lengthening the activated prothrombin time as determined by each centre according to the treatment area (depending on the coagulometer and reactants).

Or low-molecular-weight, curative dose, subcutaneous heparin (LMWH) so as to reach an anti-Xa activity corresponding to treatment areas as determined for each type of molecule (about 0.5 to 1 anti-Xa IU for most LMWHs, administered via 2 daily injections, and about 0.5 to 1.5 anti-Xa IU for tinzaparin, 1 injection daily).
Comparateur actif: UFH Late group
anticoagulant (UFH or LMWH) réintroduction 120h to 144h after hemorrhage
Médicament: UFH Late group

Either curative dose, intravenous unfractionated heparin (UFH) so as to reach an anti-Xa activity between 0.3 and 0.7 IU/mL, lengthening the activated prothrombin time as determined by each centre according to the treatment area (depending on the coagulometer and reactants).

Or low-molecular-weight, curative dose, subcutaneous heparin (LMWH) so as to reach an anti-Xa activity corresponding to treatment areas as determined for each type of molecule (about 0.5 to 1 anti-Xa IU for most LMWHs, administered via 2 daily injections, and about 0.5 to 1.5 anti-Xa IU for tinzaparin, 1 injection daily).

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
The main criterion in this study is the cumulated incidence of mortality, hæmorrhage recurrence and thromboembolic complications at 1 month
Délai: The main criterion in this study is the cumulated incidence of mortality, hæmorrhage recurrence and thromboembolic complications at 1 month

Fatal hæmorrhage proven by autopsy or sudden deaths in a clinical context strongly suggestive of hæmorrhage,

  • Fatal thromboembolic events proven by autopsy or imagery or sudden deaths in a clinical context strongly suggestive of thrombosis,
  • Any clinically significant hæmorrhage leading to temporary (> 24 hours) or permanent withdrawal of anticoagulant treatment,
  • Any symptomatic thromboembolic event in any territory, proven by imagery or surgery,
  • Any heart valve thrombosis or any intracavitary thrombus spotted by transesophageal echocardiogram performed systematically in patients with mechanical prosthesis or valvular rheumatic heart disease or AF.
The main criterion in this study is the cumulated incidence of mortality, hæmorrhage recurrence and thromboembolic complications at 1 month

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
-We will evaluate the risk/benefit balance of early versus late resumption of anticoagulant treatment,
Délai: We will evaluate at 1 month and at 3 monthsthe risk/benefit balance of early versus late resumption of anticoagulant treatment
  • Fatal hæmorrhages proven by autopsy or imagery or sudden deaths in a clinical context strongly suggestive of hæmorrhage,
  • Fatal thromboembolic events proven by autopsy or imagery or sudden deaths in a clinical context strongly suggestive of thrombosis,
  • Any clinically significant hæmorrhage leading to temporary (> 24 hours) or permanent withdrawal of anticoagulant treatment,
  • Any symptomatic thromboembolic event in any territory, proven by imagery or surgery,
  • Any heart valve thrombosis or any intracavitary thrombus spotted by transesophageal echocardiogram performed systematically in patients with mechanical prosthesis or valvular rheumatic heart disease or AF.
We will evaluate at 1 month and at 3 monthsthe risk/benefit balance of early versus late resumption of anticoagulant treatment

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Centre Hospitalier Universitaire de Saint Etienne

Les enquêteurs

  • Chercheur principal: Bernard Tardy, MD phD, CHU Saint Etienne

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude

1 janvier 2013

Achèvement primaire (Réel)

1 juin 2015

Achèvement de l'étude (Réel)

1 juin 2015

Dates d'inscription aux études

Première soumission

7 mars 2014

Première soumission répondant aux critères de contrôle qualité

17 mars 2014

Première publication (Estimation)

19 mars 2014

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Estimation)

10 mars 2016

Dernière mise à jour soumise répondant aux critères de contrôle qualité

9 mars 2016

Dernière vérification

1 mars 2016

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • 1108097
  • 2012-000286-21 (Numéro EudraCT)

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Non

Étudie un produit d'appareil réglementé par la FDA américaine

Non

produit fabriqué et exporté des États-Unis.

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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