E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Heart and lung transplantation, first days after transplantation |
Hart en long transplantatie, eerste dagen na transplantatie |
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E.1.1.1 | Medical condition in easily understood language |
Heart and lung transplantation, first days after transplantation |
Hart en long transplantatie, eerste dagen na transplantatie |
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E.1.1.2 | Therapeutic area | Body processes [G] - Physical Phenomena [G01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10053349 |
E.1.2 | Term | Pharmacokinetic study |
E.1.2 | System Organ Class | 100000004848 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary objective:
To show that the variability of whole blood total and unbound plasma tacrolimus concentrations during the first 6 days post transplantation is larger than the variation of tacrolimus concentrations in stable clinical situation.
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Primaire doel:
Het aantonen dat de variabiliteit van volbloed totale en ongebonden plasma tacrolimus concentraties gedurende de eerste dagen na transplantatie groter is dan de tacrolimus concentraties in een stabiele klinische situatie
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E.2.2 | Secondary objectives of the trial |
Secondary objectives:
• To show that unbound tacrolimus plasma concentrations can better predict the occurrence of renal dysfunction than whole blood total tacrolimus concentrations.
• Identification of variables influencing the unbound tacrolimus plasma concentrations.
• To evaluate whether variations in tacrolimus concentrations in the first days after lung transplantation in cystic fibrosis patients are higher than without cystic fibrosis.
Long-term objective:
• The data will be used to develop a kinetic model in the future in order to dose tacrolimus more accurately to prevent adverse effects of tacrolimus. |
Secundaire doelen:
• Aantonen dat de ongebonden tacrolimus plasma concentraties nierfunctiestoornissen better voorspellen dan volbloed totale tacrolimus concentraties
• Het identificeren van variabelen die de ongebonden tacrolimus plasma concentraties beïnvloeden
• Aantonen dat de variaties in tacrolimus concentraties in de eerste dagen na long transplantatie in cystic fibrose patiënten groter zijn dan zonder cystic fibrose
Lange termijn doel:
• De data zullen gebruikt worsen om een farmacokinetisch model te maken in de toekomst ter verbetering van het doseren van tacrolimus om bijwerkingen van tacrolimus te voorkomen. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients ≥ 18 years
• Patients admitted to the ICC of UMCU after heart or lung transplantation
• Treated with tacrolimus (Prograft®; Astellas Pharma Europe)
• Informed consent obtained |
• Patiënten ≥ 18 jaar
• Patiënten opgenomen op de intensive care van het UMCU na hart of long transplantatie
• Behandeling met tacrolimus (Prograft®; Astellas Pharma Europe)
• Informed consent verkregen |
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E.4 | Principal exclusion criteria |
• Patients < 18 years
• Patients who die within one day after admission to the ICC of UMCU
• Withdrawal of informed consent
• Allergy towards tacrolimus or macrolides
• Patients on total parenteral nutrition |
• Patiënten < 18 jaar
• Patiënten die overlijden binnen een dag na opname op de intensive care van het UMCU
• Intrekking van het informed consent
• Allergie voor tacrolimus of macrolides
• Patiënten behandeld met totale parenterale voeding
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E.5 End points |
E.5.1 | Primary end point(s) |
The endpoints are whole blood total tacrolimus concentrations and unbound tacrolimus plasma concentrations together with the pharmacokinetic parameters: AUC, Cmin, Cmax, Tmax, T1/2, Vd, CL, CL/F (=oral clearance). |
De uitkomstmaten van de studie zijn de volbloed totale tacrolimus concentraties en ongebonden tacrolimus plasma concentraties samen met de volgende farmacokinetische parameters: AUC, Cmin, Cmax, Tmax, T1/2, Vd, CL, CL/F (=orale klaring). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1-6, 30, 90 and 180 days after transplantation |
1-6, 30, 90 and 180 dagen na transplantatie |
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E.5.2 | Secondary end point(s) |
Variables influencing unbound plasma tacrolimus concentrations:
• Renal dysfunction
• Erythrocytes or Hematocrit
• Albumin
• alpha-1-Acid glycoprotein
• High density lipoprotein
• pH
• Daily fluid balance and body weight
• CYP3A4/CYP3A5 gene expression, and P-glycoprotein gene expression
• Hepatic dysfunction: bilirubin and ALAT will be used to quantify hepatic dysfunction
• Diarrhoea or ileus
• Cystic fibrosis
• Plasma concentrations of (val)acyclovir, (val)ganciclovir, tobramycin and trimethoprim/sulfamethoxazole, if administered, will be measured at steady state as possible additional factor causing kidney dysfunction |
Variabelen die de ongebonden tacrolimus plasma concentratie beïnvloeden:
• Nierfunctie stoornissen
• Erythrocyten of hematocriet
• Albumine
• Alpha-1-Acid glycoproteïne
• High density lipoproteïne
• pH
• Dagelijkse vloeistof balans en lichaamsgewicht
• CYP3A4/CYP3A5 gen expressie, and P-glycoproteïne gen expressie
• Leverfunctiestoornissen: bilirubine and ALAT zullen worden gebruikt om leverfunctiestoornissen te definiëren
• Diarree of ileus
• Cystic fibrose
• Plasma concentraties van (val)acyclovir, (val)ganciclovir, tobramycin en trimethoprim/sulfamethoxazole, indien toegediend, zullen gemeten worden in steady state als mogelijke additionele factor voor nierfunctiestoornissen |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-6, 30, 90 and 180 days after transplantation |
1-6, 30, 90 and 180 dagen na transplantatie |
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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 | No |
E.6.5 | Efficacy | No |
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 | No |
E.8.1.1 | Randomised | No |
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) | 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 | 2 |
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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |