E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
patients undergoing chronic dialysis |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066622 |
E.1.2 | Term | Chronic hemodialysis |
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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 is to investigate the efficacy of certoparin to prevent clotting in the extracorporeal circulation during hemodialysis at week 8. The primary endpoint is the percentage of unsatisfactory dialysis results at visit V4 (wwek 8) due to clotting or bleeding. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are • to assess the pharmacokinetics of certoparin in subjects receiving regular hemodialysis treatments including hemodiafiltration and hemofiltration, indirectly determined by the concentration-time profile of antifactor Xa activity using a chromogenic assay. • to document the safety and tolerability of certoparin over 8 weeks in subjects receiving regular hemodialysis treatments • to assess clinical efficacy by inspection of the filter system (lines, bubble catcher, dialyzer) at the site of dialysis • to assess efficacy via the percentage of clotted area in the transversal (= horizontal) plane of the filter
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Ambulatory patients ≥18 years, of either sex 2. Established end stage chronic kidney failure (CKF), requiring stable hemodialysis therapy (2-3 times per week) 3. Chronic hemodialysis therapy (including hemodiafiltration and hemofiltration) of at least 4h duration per session, for at least 3 months 4. Indication for anticoagulation during hemodialysis 5. Hemoglobin ≥10.0 g/dL at visit 1 6. Written informed consent given by the patient
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E.4 | Principal exclusion criteria |
1. Hypersensitivity/allergy to one of the components of the study drug (including chlorocresol) or to drugs with similar chemical structures 2. History of clinically significant bleeding within the last 4 weeks 3. Acute or chronic illness that can change the blood coagulation, or aggravate or terminate the clinical picture, such as peptic ulcer, active symptomatic diverticulitis, or cancer 4. Genetic abnormality of the clotting system (congenital bleeding disorder such as hemorrhagic diathesis, deficiency of coagulation factors, severe thrombocytopenia or otherwise increased bleeding risk) 5. Prior major surgery, trauma or invasive procedure of the central nervous system 6. Any prior major surgery, trauma or invasive procedure within the last 4 weeks 7. Acute or history of heparin induced thrombocytopenia type II (HIT II) 8. CRP > 300 mg/l 9. Acute severe infection (e.g. endocarditis, pneumonia, sepsis) 10. Target blood flow in device less than 200 ml/min. This holds for inclusion time point and during the study. 11. Patients using the following medicines: Dextran 40, chronic systemic glucocorticoids (≥ 4 months), thrombolytic agents and anticoagulants (e.g. phenprocoumon), glycoprotein IIb / IIIa antagonists. This holds for inclusion time point and during the study, see 6.7.5. 12. LMWH/heparin administration on three or more consecutiv days in the 5 days prior to inclusion 13. Immobilization due to cast or fracture 14. Life expectancy < 6 months or illness with very high acute mortality (> 30% per year) 15. Acute symptomatic DVT / PE 16. Acute or history of non-hemorrhagic stroke (< 3 months); hemorrhagic stroke or intracranial bleeding (< 12 months) or stroke for which thrombolytic therapy is planned 17. Acute or ongoing intracranial disease, e.g. cerebral aneurysm 18. Spinal or epidural anesthesia, lumbar punction within the last 12 hours 19. Uncontrolled hypertension, defined as diastolic blood pressure > 105 mmHg 20. Severe liver disease 21. Retinopathy, intravitreal or other intraocular bleeding or eye/ear injury 22. Participation in another clinical trial within the last 30 days 23. Subjects unlikely to comply with the requirements of the protocol. 24. Woman who are pregnant or breast feeding (pregnancy defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/ml)) o who are menstruating and capable of becoming pregnant* and not practicing a medically approved method of contraception (Pearl Index <1**) during and up to at least 4 weeks after the end of treatment. A negative pregnancy test (serum) for all women and for girls entering menarche is required with sufficient lead time before inclusion
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the nececcity to uptitrate the certoparin dose at week 8 due to clotting in the dialysis filter. |
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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 | 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 | 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 | 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 | 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 | 6 |
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 | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |