To minimize the occurrence of sub-therapeutic and supra-therapeutic C0 of tacrolimus on day 3, 7 and 10 after transplantation by basing the starting dose of tacrolimus on a dosing algorithm, rather than the standard bodyweight-only-based approach.…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
Voorkomen afstoting na niertransplantatie
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameter is the percentage of children within the target C0
range of tacrolimus on day 3, 7 and 10 after kidney transplantation.
Secondary outcome
Secondary study endpoints of the study are:
* The proportion of patients with markedly supra- (>20 ng/mL) or
sub-therapeutic (<5 ng/mL) tacrolimus C0 on day 3 after transplantation.
* The time to reach the target C0 (10-15 ng/mL).
* Incidence of BPAR and (serious) adverse events within the first 10 days after
transplantation.
Background summary
Bodyweight-based dosing of the immuosuppressant tacrolimus in children is
considered standard care, even though the available evidence is thin. Other
factors including ethnicity, age, genotype (CYP3A5), co-medication and
haematocrit influence the clearance of tacrolimus significantly. Even with
therapeutic drug monitoring (TDM), it can take up to 14 days to reach the
target tacrolimus predose concentration (C0). Underexposure to tacrolimus is
associated with rejection and overexposure to the drug with toxicity. We have
developed a dosing algorithm in our population which bases the starting dose of
tacrolimus on bodyweight, CYP3A5 genotype and donor type. The hypothesis is
that more patients will be within the target C0 range on day 3 after
transplantation using the dosing algorithm.
Study objective
To minimize the occurrence of sub-therapeutic and supra-therapeutic C0 of
tacrolimus on day 3, 7 and 10 after transplantation by basing the starting dose
of tacrolimus on a dosing algorithm, rather than the standard
bodyweight-only-based approach. More specifically, we will investigate
whether a tacrolimus starting dose based on the algorithm will lead to a
sufficient percentage of patients being within the tacrolimus target C0 on days
3, 7 and 10 after transplantation, w.r.t. the percentage found in one historic
control group of patients who have received a standard starting dose of
tacrolimus; in that case an international randomized trial might be an option.
Study design
Prospective, multi-centre, open-label, therapeutic intervention study
Intervention
All participants will receive the tacrolimus starting dose based on a dosing
algorithm which bases the dose on bodyweight, CYP3A5 genotype and donor type,
rather than the standard bodyweight-based dose.
Study burden and risks
There is no extra burden for the included children.
Wytemaweg 80
Rotterdam 3015CN
NL
Wytemaweg 80
Rotterdam 3015CN
NL
Listed location countries
Age
Inclusion criteria
* Age 2-18 years old
* Patients receiving a kidney from a blood group AB0-compatible donor
* Patients who will receive tacrolimus as part of the initial immunosuppressive therapy
* Signed written informed consent
Exclusion criteria
* Recipients of a non-renal organ transplant at the same occasion
* Recipients receiving immunosuppressive therapy (except steroid treatment) within the preceding 28 days.
* Recipients using medication known to have a relevant pharmacokinetic interaction with tacrolimus
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-001681-24-NL |
| CCMO | NL61720.078.17 |
| OMON | NL-OMON27765 |