Pharmacokinetics of tacrolimus in the first days after heart and lung transplantation

A Multi Center, Prospective, Observational, Open-label, Pharmacokinetic Study of Tacrolimus in Heart and Lung Transplantation Patients during the First Days after Transplantation - Spartacus

Status

Active, not recruiting

Phases

Phase 4

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2012-001909-24-NL

Enrollment

Registered

2012-04-27

Start date

2012-10-24

Completion date

Unknown

Last updated

2020-07-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Heart and lung transplantation, first days after transplantation MedDRA version: 19.0 Level: LLT Classification code 10053349 Term: Pharmacokinetic study System Organ Class: 100000004848

Interventions

Trade Name: Prograft®, tacrolimus Product Name: tacrolimus Product Code: RVG222236 and RVG18107 Pharmaceutical Form: Capsule, hard INN or Proposed INN: tacrolimus CAS Number: 104987-11-3 Other descrip

Eligibility

Sex/Gender

All

Inclusion criteria

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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range

Exclusion criteria

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

Design outcomes

Primary

Measure	Time frame
Main Objective: 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. ;Secondary Objective: 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.;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). ;Timepoint(s) of evaluation of this end point: 1-6, 30, 90 and 180 days after transplantation	—

Measure

Time frame

Main Objective: 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. ;Secondary Objective: 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.;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). ;Timepoint(s) of evaluation of this end point: 1-6, 30, 90 and 180 days after transplantation

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Secondary

Measure	Time frame
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;Timepoint(s) of evaluation of this end point: 1-6, 30, 90 and 180 days after transplantation	—

Measure

Time frame

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;Timepoint(s) of evaluation of this end point: 1-6, 30, 90 and 180 days after transplantation

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Countries

Netherlands

Contacts

Public ContactNational Poisons Information Center

University Medical Center Utrecht

m.a.sikma@umcutrecht.nl00318875585611

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 27, 2026