Revised dosing recommendations of ciprofloxacin for patients with impaired renal function: a bioequivalence study.

The rationale behind the guideline-recommended dose reduction of ciprofloxacin
in patients with impaired renal function is to achieve bioequivalence, defined
as drug exposure equivalent to exposure in patients with adequate renal
function receiving a regular dose. However, results from a recent previous
study by our research group showed that drug exposure is not equivalent, but
statistically significant lower in patients with impaired renal function (eGFR
< 30 ml/min/1.73m2). Therefore, we simulated on basis of a internally validated
population pharmacokinetic model alternative dosing recommendations of
ciprofloxacin for patients with impaired renal function. Results of these
simulations show that a daily dose of ciprofloxacin of 750 mg orally and 600 mg
intravenously (iv), instead of the currently administered daily dose of 500 mg
orally and 400 mg iv, should lead to equivalent drug exposure in patients with
impaired renal function, defined by an estimated glomerular filtration rate
(eGFR) below 30 ml/min/1.73m2 (eGFR < 30 ml/min/1.73m2) as in patients with
adequate renal function receiving a regular dose.

This study has been transitioned to CTIS with ID 2024-520379-28-00 check the CTIS register for the current data.

To compare exposure to ciprofloxacin between patients with impaired renal
function (eGFR < 30 ml/min/1.73m2) admitted to a general ward in the AMC or
OLVG location Oost receiving the revised reduced doses (test), patients with
impaired renal function (eGFR < 30 ml/min/1.73m2) admitted to a general ward at
Noordwest Ziekenhuisgroep recieving the revised dose as standard of care (test)
and patients with adequate renal function receiving regular doses (reference),
by investigating whether exposure in the first 24 hours of treatment (AUC0-24)
is bioequivalent between both patient groups (test/reference).

A multi-center, multiple-dose, non-randomized, open, bioequivalence study will
be conducted at the Amsterdam UMC - location AMC, at the OLVG Oost and
Noordwest Ziekenhuisgroep location Alkmaar.

1) Treatment with the revised reduced doses of ciprofloxacin for adult patients
with impaired renal function receiving study medication at AMC or OLVG location
Oost and recieving standard of care at Noordwest Ziekenhuigroep location
ALkmaar. Patients with adequate renal function will be treated with the regular
doses.
2) A maximum of four venapunctures in the first 48 hours of treatment with
ciprofloxacin, obtaining a maximum of 16 ml blood in total.

Patients with impaired renal function admitted to a general ward at the AMC or
OLVG location Oost may benefit directly from participating in this study, since
they will be treated with revised reduced doses of ciprofloxacin, which are
expected to lead to exposure comparable with the exposure achieved with regular
doses in patient with adequate renal function, and as such may be more adequate
than the currently recommended dosing recommendations for this patient group.
Patients with impaired renal function admitted to a general ward at Noordwest
Ziekenhuigroep do not directly benefit from participation in this study as they
will be treated by their own doctor in the standard way, according to the local
guideline. The local guideline in Noordwest Ziekenhuisgroep already recommends
a dose reduction in patients with an impaired renalfunction identical to the
calculated revised reduced doses of ciprofloxacin.

Risks imposed by participation are considered negligible. By using population
pharmacokinetic (PK) modeling, relevant individual pharmacokinetic parameters,
which are the basis of the calculation of the primary endpoint (AUC0-24), can
be assessed on the basis of only four blood samples per patient. As a result,
the participation burden and risk for the individual patient is low.