No registrations found.
ID
Source
Brief title
Health condition
Cancer-related pain
Sponsors and support
Intervention
Outcome measures
Primary outcome
To prove bioequivalence in fentanyl exposure (measured as area under the curve (AUC)) pre- and post-rotation.
Secondary outcome
To associate the occurrence and severity of adverse events and pain scores pre- and post-rotation with pharmacokinetic parameters.
Background summary
Rationale: Fentanyl is a strong-acting, widely used opioid in the treatment of cancer-related
pain. In hospitalized patients with severe pain, fast dose titration of fentanyl can be performed
by combined continuous and bolus subcutaneous administration. When stable pain control is
reached, a rotation to transdermal patches can be done. The fentanyl rotation-scheme used in
Erasmus MC was previously based on data concerning rotation from intravenous fentanyl.
Based on a PK modeling study with subcutaneous fentanyl (METC nr.09-332) and clinical
observations, the fentanyl rotation scheme has been optimized and the rotation scheme is now
used in standard clinical practice. However, this scheme has never been validated
prospectively on PK and PD-endpoints.
Objective: To prospectively validate the pharmacokinetics of fentanyl during the current
standard-of-care rotation scheme from subcutaneous to transdermal fentanyl administration in
patients with moderate to severe cancer-related pain. We aim to prove bio-equivalence before
and after fentanyl rotation using the area under the curve (AUC).
Study design: Real-life observational study in patients who are rotated from a subcutaneous
to a transdermal administration route for fentanyl according to the current standard of care in
the Erasmus Medical Centre. Due to the use of the previously developed model the number of
blood samples will be very sparse. We plan to collect 2-3 randomly taken samples prior to the
rotation and 2-3 random samples after the rotation. The acquired exposure quantified as AUC
will be compared pre- and post-rotation with a paired t-test. Patients complete the study when
all blood samples are taken or when the patient is discharged from the hospital.
Study population: Cancer patients who are hospitalized and who are being treated with
subcutaneous fentanyl and are expected to switch towards transdermal fentanyl using a 1:1
dose conversion ratio. To prevent interference with fentanyl pharmacokinetics, rescues are
only allowed to be an opioid other than fentanyl 12 hours prior to the rotation.
Intervention: Not applicable
Main study parameters/endpoints:
- Primary endpoint
o To prove bioequivalence in fentanyl exposure (measured as area under the
curve (AUC)) pre- and post-rotation.
- Secondary endpoint
o To associate the occurrence and severity of adverse events and pain scores
pre- and post-rotation with pharmacokinetic parameters.
Study objective
This study aims to prove bio-equivalence pre- and post-rotation and therefore validate the standard of care clinical practice regarding the rotation from subcutaneous to transdermal administration of fentanyl in the Erasmus MC on PK and PD endpoints.
Study design
1
Inclusion criteria
Age > 18 years
Able to understand the written information and able to give informed consent.
Current treatment with subcutaneous fentanyl and planned to rotate to transdermal
fentanyl
To ensure steady-state kinetics, patients must have been treated with
subcutaneous fentanyl for at least 40 hours prior to the rotation and have been
treated with a stable fentanyl dose at least 20 hours prior to the rotation This way,
fentanyl pharmacokinetics are at steady-state.
Exclusion criteria
Patients that use short-acting fentanyl via the oral, (oral mucosal, sublingual),
intranasal or subcutaneous administration route 12 hours prior to the rotation will
be excluded as this influences the pharmacokinetic profile of the subcutaneous
administration. This implicates that patients will be prescribed oral short acting
oxycodone or morphine 12 hours before rotation as these are mostly used next to
treatment with transdermal fentanyl.
Patients that use strong CYP3A4 inhibitors or inducers will be excluded as the
model did not account for the influence of strong CYP3A4 inhibition or induction on
fentanyl pharmacokinetics while the effects have been shown in multiple studies
Patients that are rotated using a dose conversion ratio other than 1:1 will also be
excluded.
Design
Recruitment
IPD sharing statement
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL9839 |
| Other | Erasmus MC : MEC 2021-0581 |