E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with clinical indication for pharmacological thromboprophylaxis and slow low efficient daily dialysis (SLEDD). |
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E.1.1.1 | Medical condition in easily understood language |
Patients with clinical indication for pharmacological thromboprophylaxis and slow low efficient daily dialysis. |
Potilas tarvitsee laskimotukoksia estävää lääkitystä ja mata-annoksista munuaisten korvaushoitoa. |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutic techniques [E02] |
MedDRA Classification |
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 the pharmacokinetics of tinzaparin during SLEDD by comparing plasma anti-FXa levels when tinzaparin is administered into the inlet line of hemodialysis circuit after 5 minutes from the start of dialysis either as a single bolus or as a bolus and continuous infusion. The primary outcome measure will be plasma anti-FXa concentration at 4 hours from the onset of SLEDD |
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E.2.2 | Secondary objectives of the trial |
To evaluate the dialyzer circuit performance |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age over 18 years
• Critically ill patients requiring intensive care
• Indication for pharmacological thromboprophylaxis
• Written informed consent obtained from the patient or his/her legal representative.
• Indication for SLEDD, any of following:
- AKI stage 3 of KDIGO (20): serum creatinine concentration of more than 354 umol/l or greater than 3 times the baseline creatinine level OR anuria (urine output of 100 ml/day) for more than 12 hours OR oliguria: <0.3 ml/kg/h for more than 24 hours OR 500 ml/day
- the presence of clinically significant organ edema (e.g., pulmonary edema, elevated intraabdominal pressure, significant peripheral swelling) together with oliguria or anuria
- Dialysis dependence after CRRT Ci-Ca
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E.4 | Principal exclusion criteria |
• Other indications for anticoagulant therapy than thromboprophylaxis (including sodium citrate for CRRT)
• Any long-term anticoagulant or antithrombotic medication, except for low-dose aspirin (<150 mg daily)
• Treatment with tinzaparin or any other LMWH or heparin within 24 hours of study inclusion
• Known heparin induced thrombocytopenia (HIT), or hypersensitivity to tinzaparin or any other heparin
• Known pregnancy
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome measure is plasma anti-FXa concentration at 4 hours from the onset of SLEDD. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
at 4 hours from the onset of SLEDD. |
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E.5.2 | Secondary end point(s) |
Blood samples
- Routine blood test (i.e. blood counts, INR, renal parameters, creatinine, C reactive protein and bilirubin)
- Anti-FXa
- Frozen blood samples :
Thrombin generation (CAT)
AT 3, FIDD, F1 and F2, TAT, TFPI
- At the end of the SLEDD dialysis visual clotting will be evaluated (clotting score)
- During SLEDD following parameters will be registered:
Transmembrane pressure
Inlet pressure
Outlet pressure
- Total duration of SLEDD
- Following adverse events will be registered and treated according to normal practice
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Routine blood test before SLEDD treatment
- Anti-FXa will be measured at 0, 4 (Tmax), 8 and 24 hours from the onset of the SLEDD
- Frozen blood samples will be collected at 0, 4, 8 and 24 hours from the onset of the SLEDD
Clinical events
- At the end of the SLEDD dialysis visual clotting will be evaluated
- During SLEDD following parameters will be registered at 1, 2, 4 and 8 hours:
o Transmembrane pressure
o Inlet pressure
o Outlet pressure
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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 | 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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 |
different dosing of same medical product |
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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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | 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 | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |