E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Allograft vascular thrombosis |
Thrombose vasculaire allogreffe |
|
E.1.1.1 | Medical condition in easily understood language |
Allograft vascular thrombosis |
Thrombose vasculaire allogreffe |
|
E.1.1.2 | Therapeutic area | Not possible to specify |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10072226 |
E.1.2 | Term | Renal vascular thrombosis |
E.1.2 | System Organ Class | 10038359 - Renal and urinary disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To optimize the dose of enoxaparin in order to achieve appropriate anti-Xa activity in pediatric renal transplantation. |
Optimiser la dose d’énoxaparine afin d’obtenir une activité anti-Xa appropriée en transplantation rénale pédiatrique. |
|
E.2.2 | Secondary objectives of the trial |
• To maintain target-range anti-Xa activity at all assessments during the first week of treatment • To assess the safety of this approach.
|
• Maintenir l’activité anti-Xa cible lors de toutes les évaluations pendant la première semaine de traitement • Évaluer la sécurité de cette approche.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) pediatric renal transplant recipients 2) aged > 2 years and <18 years 3) with an indication for enoxaparin treatment in the first post-transplant week according to the local transplant team such as inherited or acquired thrombotic disorders (eg. but not exclusive protein C, protein S, and antithrombin III deficiency; factor V Leiden mutation (FV506Q), prothrombin mutation (G20210A), mutation in the MTHFR gene (C677T), and antiphospholipid antibodies (anticardiolipin antibodies and lupus anticoagulants), history of thrombosis, donor age < 2 years, recipient age < 5 years, cold ischemia time >24h, multiple renal vessels 4) informed consent form signed by the legal guardian(s) 5) affiliated to a health insurance system
|
1) receveur d’une transplantation rénale 2) âgé > 2 ans et <18 ans 3) avec une indication, selon l’équipe locale de transplantation, d’un traitement par énoxaparine au cours de la première semaine post-transplantation telles que les thrombophilies héréditaires ou acquises (par ex. mais non exclusif: déficit en protéine C, protéine S et antithrombine III; mutation du facteur V Leiden (FV506Q), mutation du gène de la prothrombine (G20210A), mutation du gène MTHFR (C677T), et/ou anticorps antiphospholipides (anticorps anticardiolipine et anticoagulants lupus), antécédents de thrombose, âge du donneur <2 ans, âge du receveur <5 ans, temps d’ischémie froide >24h, vaisseaux rénaux multiples 4) recueil du consentement signé du(des) représentant(s) légal(aux) 5) affilié ou bénéficiaire d’une sécurité sociale
|
|
E.4 | Principal exclusion criteria |
1) per-transplant technical surgical problems 2) pre-inclusion allograft thrombosis (before randomization and enoxaparin administration) 3) peri-operative thrombosis or bleeding (before randomization and enoxaparin administration) 4) peri-operative hemodynamic instability 5) medical history of heparin-induced thrombocytopenia 6) allergic reaction to enoxaparin or excipients 7) pregnancy 8) LMWH prophylactic before transplant
|
1) problèmes chirurgicaux techniques pré-greffe 2) thrombose du greffon avant inclusion (avant randomisation et administration de l’enoxaparine) 3) thrombose ou saignement péri-opératoire (avant randomisation et administration de l’enoxaparine) 4) instabilité hémodynamique péri-opératoire 5) antécédents de thrombopénie induite par l’héparine 6) hypersensibilité à l’enoxaparine ou à l’un des excipients 7) grossesse 8) HBPM en prophylactique avant greffe
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Anti-Xa activity within target ranges (0.3-0.5 IU/mL) 28-30 hours after initiation of treatment. |
Activité anti-Xa dans les cibles (0,3 à 0,5 UI/mL) 28 à 30 heures après le début du traitement. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
28-30 hours after initiation of treatment |
28 à 30 heures après le début du traitement |
|
E.5.2 | Secondary end point(s) |
• Time to achieve a target anti-Xa activity (0.3-0.5 IU/mL) • Anti-Xa activity within target ranges from H28-30 to D7 after initiation of treatment (same method as primary endpoint) • Graft thrombosis : assessed by allograft ultrasound • Enoxaparin-related side effects during the first postoperative month: bleeding (all localisations), graft hematoma (presence/absence): assessed by ultrasound • Allograft bleeding: bleeding with post-operative transfusion • Enoxaparin induced thrombopenia
|
• Temps nécessaire pour atteindre une activité anti-Xa cible (0,3 à 0,5 UI/mL) • Activité anti-Xa dans les cibles allant de H28-30 à D7 après le début du traitement • Thrombose artérielle et ou veineuse du greffon • Effets secondaires liés à l’énoxaparine au cours du premier mois postopératoire : saignement (toutes localisations), hématome du greffon (présence/absence) • Saignement du greffon: saignement nécessitant ou non une transfusion post-opératoire • Thrombopénie induite par l’énoxaparine
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
- H28-30 to D7 after initiation of treatment - D30 |
- H28-30 à J7 après le début du traitement - J30 |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Ajustement de dose empirique |
Empirical dose adjustment |
|
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 24 |
E.8.9.1 | In the Member State concerned days | 30 |