E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Catheter related venous or arterial thrombosis |
Trombosi arteriosa o venosa correlata a catetere |
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E.1.1.1 | Medical condition in easily understood language |
Blood clot in a vein or artery related to a catheter |
Coagulo arterioso o venoso correlato a uso di catetere |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10043565 |
E.1.2 | Term | Thromboembolic event |
E.1.2 | System Organ Class | 100000004866 |
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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 characterize the pharmacokinetic /pharmacodynamic profile of a 7-day treatment with oral rivaroxaban |
caratterizzare il profilo farmacocinetico e farmacodinamico di un trattamento per 7 giorni con rivaroxaban orale |
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E.2.2 | Secondary objectives of the trial |
• to assess the incidence of major bleeding and clinically relevant non-major bleeding• to assess the incidence of symptomatic recurrent thromboembolism and • to assess asymptomatic deterioration in the thrombotic burden on repeat imaging |
valutare l’incidenza di emorragia maggiore e di emorragia non maggiore clinicamente rilevante, valutare l’incidenza di tromboembolismo sintomatico ricorrente valutare il deterioramento asintomatico del carico trombotico alla rivalutazione radiologica
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Children from birth to less than 6 months with documented symptomatic or asymptomatic catheter-related venous or arterial thrombosis who will enter their last 7 days of intended anticoagulant treatment.2. Gestational age at birth of at least 37 weeks.3. Hemoglobin, platelets assessed within 10 days prior to enrollment.4. Oral feeding/nasogastric/gastric feeding for at least 10 days. 5. Informed consent provided. |
1. Bambini dalla nascita a meno di 6 mesi affetti da trombosi arteriosa o venosa sintomatica od asintomatica documentata, correlata al catetere, trattati con terapia anticoagulante per almeno 2 settimane. 2. Età gestazionale alla nascita di almeno 37 settimane. 3. Emoglobina, piastrine, alanin-aminotransferasi (ALT) e bilirubina diretta valutate entro 10 giorni prima dell’arruolamento. 4. Alimentazione orale/nasogastrica/gastrica per almeno 10 giorni. 5. Consenso informato rilasciato.
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E.4 | Principal exclusion criteria |
1. Active bleeding or high risk for bleeding contraindicating anticoagulant therapy, including history of intra-ventricular bleeding.2. Symptomatic progression of thrombosis during preceding anticoagulant treatment.3. Planned invasive procedures, including lumbar puncture and removalof non-peripherally placed central lines during study treatment.4. Known hepatic disease associated with coagulopathy leading to a clinically relevant bleeding risk. Creatinine > 1.5 times the baseline value in children aged 1 month and older and creatinine > 1.5 mg/dl in children younger than 1 month5. Hypertension defined as 6. History of gastrointestinal disease or surgery associated with impaired absorption.7. Platelet count < 100 x 109/L.8. Concomitant use of strong inhibitors of both cytochrome P450 isoenzyme 3A4 (CYP3A4) and P-glycoprotein (P-gp).9. Concomitant use of strong inducers of CYP3A4.10. Indication for anticoagulant therapy other than current thrombosis.11. Indication for antiplatelet therapy or NSAID therapy.12. Hypersensitivity to rivaroxaban or its excipients.13. Participation in a study with an investigational drug or medical device within 30 days prior to enrollment |
1. Emorragia in atto o rischio elevato di emorragia che controindichi una terapia anticoagulante, compresa l’anamnesi di emorragia intra-ventricolare 2. Progressione sintomatica della trombosi durante il precedente trattamento anticoagulante 3. Procedure invasive programmate compresa la puntura lombare e la rimozione di linee centrali poste alla periferia durante il trattamento dello studio 4. Malattia epatica associata a: coagulopatia che comporti un rischio emorragico clinicamente rilevante o livello di alanin-aminotransferasi (ALT)> 5x il livello superiore della norma (ULN) o bilirubina totale (TB) > 2x ULN con bilirubina diretta > 20% il totale 5. Creatinina> 1,5 volte la norma 6. Ipertensione definita come >95° percentilea 7. Storia di malattia gastrointestinale o di intervento chirurgico associato ad alterato assorbimento 8. Conta piastrinica <100 x 109/L 9. Impiego concomitante di forti inibitori dell’isoenzima del citocromo P450 3A4 (CYP3A4) e della P-glicoproteina (P-gp) 10. Impiego concomitante di forti induttori di CYP3A4 11. Indicazione per una terapia anticoagulante diversa dalla trombosi attuale 12. Indicazione per una terapia antiaggregante o per una terapia antinfiammatoria non-steroidea (FANS) 13. Ipersensibilità a rivaroxaban od ai suoi eccipienti 14. Partecipazione ad uno studio con un farmaco sperimentale o un dispositivo medico entro 30 giorni prima dell’arruolamento. a vedere l’Appendice 17.1.2.
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E.5 End points |
E.5.1 | Primary end point(s) |
PK/PD modeling, using population approaches will be used to describe the pharmacokinetics of rivaroxaban, and to relate anticoagulant parameters of rivaroxaban with plasma concentrations. |
Risultati della farmacocinetica (PK) / farmacodinamica (PD) (tempo di protrombina, tempo di tromboplastina parziale attivata ed attività anti-fattore Xa) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After last patient. last visit |
dopo LPLV |
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E.5.2 | Secondary end point(s) |
1. The occurrence of recurrent venous or arterial thromboembolism and asymptomatic deterioration in thrombotic burden will be summarized.2. All safety analyses will be performed on the safety population. Bleeding events observed later will be described separately. Individual listings of major and clinically relevant non-major bleeding will be provided. 3. The occurrence of recurrent venous or arterial thromboembolism and asymptomatic deterioration in thrombotic burden |
Insieme di emorragia maggiore e non maggiore clinicamente rilevante. Insieme di tutto il tromboembolismo ricorrente sintomatico e di deterioramento asintomatico del carico trombotico alla rivalutazione radiologica. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. After LPLV 2.The analysis will primarily focus on bleeding that occurred during or within 2 days after stop of rivaroxaban
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1.Dopo LPLV 2.Sanguinamenti avventi durante o entro 2 giorni dall'interruzione del trattamento con rivaroxaban |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
First study in age range 0-6 months |
Primo studio nella fascia 0-6 mesi |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
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 | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Austria |
Canada |
France |
Germany |
Israel |
Italy |
Netherlands |
Poland |
Spain |
United States |
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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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 21 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 21 |