E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with renal impairment defined by a creatinin clearance between 20 and 50 ml/min and undergoing a major orthopaedic surgery (hip fracture, total hip replacement and total knee replacement) |
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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 | 10038474 |
E.1.2 | Term | Renal insufficiency |
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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 | 10020100 |
E.1.2 | Term | Hip fracture |
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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 | 10023476 |
E.1.2 | Term | Knee osteoarthritis |
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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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020108 |
E.1.2 | Term | Hips osteoarthritis |
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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 evaluate between D5 and D10, the incidence of major bleedings after a daily subcutaneous injection of fondaparinux 1,5 mg during at least 5 days for prevention of venous thromboembolic events after major orthopaedic surgery (TKR, THR and HF) in patients with a CrCl between 20 and 50 ml/min (estimated by Cockcroft and Gault formula). |
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E.2.2 | Secondary objectives of the trial |
to evaluate: • The incidence of major bleedings at 1 month ± 5 days • The incidence of clinically significative bleedings between D5 and D10 and at 1 month ± 5 days • The incidence of symptomatic venous thromboembolic events (DVT and PE) between D5 and D10 and at 1 month ± 5 days • Pharmacodynamic parameters based on Xa activity (absorption half-life and elimination clearance of distribution volume and their variability) of fondaparinux based on a non-linear model at mixed effect and to compare the observed real clinical data with those simulated and described in MA file. • Estimation of haemorrhagic and thromboembolic risk factors. • Estimation of inter-laboratories variability in the measure of anti-Xa activity with fondaparinux |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patient affiliated with or a beneficiary of a social security category: • age > 18 years old, • requiring a major orthopaedic surgery (THR, TKR, HF) whatever procedure techniques are used, 1st indication or resumption, • requiring an antithrombotic prophylaxis, • presenting a renal impairment defined by a creatinin clearance (CrCl) between 20 and 50 ml/min calculated by Cockcroft and Gault’s formula, • having signed the inform consent form.
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E.4 | Principal exclusion criteria |
• contra-indications to fondaparinux, • history of heparin inducted thrombopenia (HIT), • history of venous thromboembolic event, • Haemorrhagic diathesis, • PT < 50 %, aPTT > 1,5 of control value, platelets < 100 G/l. incapacity to understand protocol
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E.5 End points |
E.5.1 | Primary end point(s) |
• Major bleeding (occuring between D5 and D10) is defined by: - an exteriorised bleeding with a bleeding index > 2 (g/dl of haemoglobin decrease + number of units transfused) - a bleeding needing a resumption surgery - a bleeding affecting a critical organ (ocular, retroperitoneal, pericardial, intra-cranial, intra-medullary, intramuscular with compression) - a fatal bleeding
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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 | No |
E.6.6 | Pharmacokinetic | No |
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) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 17 |
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 | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |