Clinical trial NCT06368856: Pharmacology of Mupirocin in Nasal Application in Healthy Volunteers: Monocentric Study
Official title: Pharmacology of Mupirocin in Nasal Application in Healthy Volunteers: Monocentric Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Healthy
Staphylococcus Aureus Infection
Keywords: Staphylococcus Aureus
Mupirocin
Pharmacokinetic
Lead sponsor: Centre Hospitalier Universitaire de Saint Etienne
Sponsor class: OTHER
First posted: 2024-04-16
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Single-center, randomized, open-label pharmacokinetic study of mupirocin in 40 healthy subjects with 2 randomization :

* first randomization - single dose part : 50mg or 500mg of mupirocin
* wash-out: one month
* second randomization - repeated doses part: 50mg mupirocin twice a day or 50 mg 3 times a day 500mg mupirocin twice a day or 500mg mupirocin 3 times a day
Primary purpose: OTHER

Brief summary: Mupirocin is an old antibiotic used topically since the 1970s. Initially used in the treatment of skin infections for its antistaphylococcal action, it is now part of the decolonization strategy for Staphylococcus aureus (SA) carriage, in association with chlorhexidine. This decolonization strategy has been recommended in France for preoperative cardiac surgery in nasal SA carriers since 2013 by the French Hospital Hygiene Society, and recommended for cardiac and orthopedic surgery in SA carriers by the World Health Organization (WHO) since 2016. This strategy includes nasal decolonization using mupirocin ointment nasally (2 to 3 applications/day), a daily shower with chlorhexidine soap and + /- mouthwashes all over 5 days, often pre-operatively.

As a result, mupirocin is now widely used throughout the world, all the more so as, for reasons of ease of organization, many centers use this decolonization procedure universally (i.e. without prior screening for Staphylococcus aureus carriage), thus further increasing the use of this molecule.

Mupirocin administration methods are very vague, ranging from 2 to 3 applications per day and the application of "a match head", i.e. 50 mg, to 500 mg per nostril.

Mupirocin is bacteriostatic at low doses, becoming bactericidal at higher concentrations; low concentrations could favor the selection of resistance, so using the most effective dosage seems essential. This lack of precision in administration is linked to an almost complete ignorance of the pharmacokinetics of mupirocin and its metabolite (monic acid) after nasal application.

It therefore seems essential to conduct a pharmacokinetic study of this molecule, in order to eventually offer patients the regimen with the administration methods offering the best characteristics in terms of dosage and efficacy.


Eligibility criteria: Inclusion Criteria:

* Subject affiliated or entitled to a social security plan
* Subject having signed the consent to participate in the study

Exclusion Criteria:

* Pregnancy in progress
* Acute or chronic rhinorrhea
* Allergy to mupirocin calcium or excipients
* Any medication taken during the week preceding the beginning of the study
* Notable medical history (cardiovascular, pulmonary, neurological pathology, etc.)

Primary outcomes:
measure: plasma concentrations of mupirocin
timeFrame: 0 hours 30 after mupirocin application (Single dose part)
measure: plasma concentrations of mupirocin
timeFrame: 1 hours after mupirocin application (Single dose part)
measure: plasma concentrations of mupirocin
timeFrame: 2 hours after mupirocin application (Single dose part)
measure: intranasal concentrations of mupirocin
timeFrame: 1 hours after mupirocin application (Single dose part)
measure: intranasal concentrations of mupirocin
timeFrame: 2 hours after mupirocin application (Single dose part)
measure: intranasal concentrations of mupirocin
timeFrame: 4 hours after mupirocin application (Single dose part)
measure: intranasal concentrations of mupirocin
timeFrame: 6 hours after mupirocin application (Single dose part)
measure: intranasal concentrations of mupirocin
timeFrame: 8 hours after mupirocin application (Single dose part)
measure: intranasal concentrations of mupirocin
timeFrame: 12 hours after mupirocin application (Single dose part)
Secondary outcomes:
measure: presence of Staphylococcus aureus
timeFrame: Days: 5 after mupirocin application (Repeated dose part)
measure: presence of Staphylococcus aureus
timeFrame: Days: 6 after mupirocin application (Repeated dose part)
measure: presence of Staphylococcus aureus
timeFrame: Days: 30 after mupirocin application (Repeated dose part)
measure: presence of Staphylococcus aureus
timeFrame: Days: 90 after mupirocin application (Repeated dose part)
measure: urinary concentrations of monic acid
timeFrame: Days: 2 after mupirocin application (Repeated dose part)
measure: urinary concentrations of monic acid
timeFrame: Days: 3 after mupirocin application (Repeated dose part)
measure: urinary concentrations of monic acid
timeFrame: Days: 4 after mupirocin application (Repeated dose part)
measure: urinary concentrations of monic acid
timeFrame: Days: 5 after mupirocin application (Repeated dose part)
Other outcomes:
Locations:
city: Saint-Étienne
country: France
facility: CHU de SAINT-ETIENNE
Study officials:
affiliation: CHU SAINT-ETIENNE
name: Kasra AZARNOUSH, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: