Rationale and Design of a Phase III Safety Trial of Idarucizumab in Children Receiving Dabigatran Etexilate for the Treatment and Secondary Prevention of Venous Thromboembolism
Notice bibliographique
Résumé
Abstract Introduction: The frequency of venous thromboembolism (VTE) is increasing in children. Dabigatran etexilate (DE), the prodrug of the direct thrombin inhibitor dabigatran is approved for use in adults for the treatment and secondary prevention of VTE. However, DE is not approved for the use in children and is currently being evaluated for the treatment and secondary VTE prevention within ongoing pediatric DE trials. With the increasing use of oral anticoagulants for VTE treatment and prevention in adults, agents that can rapidly reverse anticoagulant effects in patients who require emergency surgery/urgent procedure, or who have a rare event of life-threatening or uncontrolled bleeding, will complement treatment strategies for managing bleeds or urgent interventions in patients receiving dabigatran. Idarucizumab is a humanized monoclonal antibody fragment that provides immediate, complete and sustained reversal of the anticoagulation effects of dabigatran. The safety and efficacy of idarucizumab have been confirmed in adult patients receiving DE; however, the safety of idarucizumab in children with VTE remains to be established. The present trial will investigate the safety of idarucizumab in children with VTE who have participated in two ongoing clinical trials investigating DE. Methods: A phase III, open-label, single arm, global multicenter safety trial (approximately 25-40 sites; approximately 10 countries) is planned in children (aged < 18 years; n = ~5) recruited within the ongoing dabigatran pediatric clinical program for treatment or secondary prevention of VTE. Children who require a rapid reversal of anticoagulation will be eligible for trial inclusion: those with life-threatening/uncontrolled bleeding (group A) and those without bleeding but needing emergency surgery/urgent procedures (group B). Patients will receive a single intravenous dose of idarucizumab (up to 5 g, calculated according to the patient's body weight, administered in two equally divided infusions or injections given not more than 15 minutes apart) and will be monitored for 30 days. Results: The primary endpoint will be the safety of idarucizumab assessed by the occurrence of drug-related adverse events (including immune reactions) and all-cause mortality. The secondary endpoints will be the percentage change of coagulation tests (diluted thrombin time [dTT] and ecarin clotting time [ECT]) at 30 minutes post-dose versus pre-dose, the time to achieve complete reversal, duration of complete reversal of dabigatran's anticoagulant effect sustained at 24 hours post-dose based on coagulation tests (dTT and ECT), and the formation of antidrug antibodies at 30 days post-dose. Cessation of bleeding, bleeding status and other clinical conditions that may contribute to bleeding (group A patients only) will also be assessed. Data will be reported using descriptive statistics and all treated patients will be included in the safety analysis. Conclusion: This trial will report the safety of idarucizumab in children with VTE who require the rapid, complete and sustained reversal of the anticoagulant effects of dabigatran. Disclosures Albisetti: Boehringer Ingelheim: Other: Pediatric Expert Working Group. Schlosser:Boehringer Ingelheim: Employment. Brueckmann:Boehringer Ingelheim: Employment. Gropper:Boehringer Ingelheim: Employment. Glund:Boehringer Ingelheim: Employment. Tartakovsky:Boehringer Ingelheim: Employment. Reilly:Boehringer Ingelheim: Employment.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,036 | 0,018 |
| Méta-épidémiologie (sens strict) | 0,002 | 0,001 |
| Méta-épidémiologie (sens large) | 0,002 | 0,002 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,002 | 0,003 |
| Communication savante | 0,002 | 0,002 |
| Science ouverte | 0,002 | 0,001 |
| Intégrité de la recherche | 0,003 | 0,005 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,010 | 0,003 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».