E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-surgical below-knee injury, immobilization with a plaster cast or brace, venous thromboembolism, bleeding events. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10049909 |
E.1.2 | Term | Venous thromboembolism prophylaxis |
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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 |
The primary objective of the study is to demonstrate the superiority of fondaparinux 2.5 mg (1.5 mg in patients with a creatinine clearance between 30 and 50 mL/min) once daily versus LMWH (nadroparin 2850 anti-Xa IU, 0.3 mL, once daily), with respect to the occurrence of VTE or death up to complete mobilization, corresponding to cast or brace removal, in patients requiring rigid or semi-rigid immobilization for at least 21 days and up to 45 days for an isolated non-surgical below-knee injury. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Male or female patients 18 years of age or older, Requiring rigid or semi-rigid immobilization (e.g. with a plaster cast or brace) for at least 21 days and up to 45 days, because of isolated non-surgical below-knee injury, With a no weight-bearing recommendation at the time of inclusion (partial weight bearing is permitted e.g. crutches, walking cast, relief shoes), Presenting at least one of the following risk factors for VTE: below-knee fracture or Achilles tendon rupture, age ≥40 years, body mass index > 30 kg/m2, oestrogen-containing hormonal replacement therapy or oral contraception, active cancer (treatment on going or stopped for less than one year) history of venous thomboembolism congenital or acquired hypercoagulable state Requiring thromboprophylaxis according to the Investigator`s judgement up to complete mobilization, corresponding to cast or brace removal. Able and willing to provide written informed consent. |
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E.4 | Principal exclusion criteria |
Delay between injury and randomization greater than two days, Treatment with antithrombotic or anticoagulant therapy, including low-dose anticoagulation, for more than 2 days prior to randomization, Anticoagulant therapy required or likely to be required during the study period for another reason (e.g. planned surgery justifying pharmacological thromboprophylaxis, curative dose for treatment of VTE, etc.) Known hypersensitivity to fondaparinux or nadroparin or their excipient, Known history of heparin-induced thrombocytopenia, Women of childbearing potential not using a reliable contraceptive method throughout the study period Women pregnant or breast-feeding during the study period. Exclusion criteria based on risk of bleeding associated with fondaparinux or other anticoagulant therapy: Active, clinically significant bleeding, Clinically significant bleeding within the past six months, Major surgery within the previous three months, Intraocular (other than cataract), spinal, and/or brain surgery within the previous twelve months, Haemorrhagic stroke within the previous twelve months, XM2008/00032/01 CONFIDENTIAL ART109350 31 CONFIDENTIAL XM2008/00032/01 ART109350 32 Severe head injury within the previous three months, Documented congenital or acquired bleeding tendency/disorder(s), Previous (within 12 months) or active or currently treated peptic ulcer disease, Uncontrolled arterial hypertension (systolic blood pressure over 180 mm Hg or diastolic blood pressure over 110 mm Hg), Treatment with more than one antiplatelet agents (e.g. clopidogrel and aspirin) at any dose, Need for chronic aspirin at doses&#8805; 325 mg or chronic NSAIDs, Bacterial endocarditis, Severe hepatic impairment, Calculated creatinine clearance < 30 mL/min, Thrombocytopenia ( <100x109/L) Body weight < 50 kg. Other exclusion criteria related to trial methodology: Any condition that could prevent the patient from providing written informed consent or from adhering to study treatment, Life expectancy under six months, Participation in any study using an investigational drug during the previous three months, Patient in whom V3 is unlikely to be feasible (e.g. patient moving house) |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is venous thromboembolism or death up to complete mobilization, corresponding to cast or brace removal (plus two days). |
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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 | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
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 | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 12 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 62 |
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 | Information not present in EudraCT |
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 | 0 |
E.8.9.1 | In the Member State concerned days | |
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 | 0 |