Pharmacology of Mupirocin in Nasal Application in Healthy Volunteers: Monocentric Study (MUPIPHARM)

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.

Study Overview

• Status: Recruiting
• Conditions: Healthy; Staphylococcus Aureus Infection
• Intervention / Treatment: Drug: Mupirocin (50 mg); Biological: blood samples after Single dose part; Diagnostic test: nasal swab after Single dose part; Other: Collection of urine after Single dose part; Drug: Mupirocin (500 mg); Diagnostic test: nasal swab during Repeated dose part; Other: Collection of urine during Repeated dose part; Other: nasal swab after Repeated dose part

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Carine LABRUYERE, CRA; Phone Number: +33 (0)477120469; Email: carine.labruyere@chu-st-etienne.fr
• Study Contact Backup: Name: Kasra AZARNOUSH, MD PhD; Phone Number: +33 (0)477829446; Email: Kasra.Azarnoush@chu-st-etienne.fr

Study Locations

• France
  • Saint-Étienne, France
    • Recruiting
    • CHU de Saint-Etienne
    • Sub-Investigator: Philippe BERTHELOT, MD PhD
    • Sub-Investigator: Anne CARRICAJO, MD
    • Sub-Investigator: Elisabeth BOTELHO-NEVERS, MD PhD
    • Principal Investigator: Kasra AZARNOUSH, MD PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Single dose part : 50mg mupirocin; - Single dose part = single dose of 50 mg mupirocin in each nostril	Drug: Mupirocin (50 mg); 50 mg de mupirocin; Other Names: Bactroban; Biological: blood samples after Single dose part; 3 blood samples will be performed sampling time ater application of mupirocin (single dose part): 00h30, 1h00, 02h00; Diagnostic test: nasal swab after Single dose part; 7 nasal swab for the detection of S. aureus (type Swab) will be performed after application of mupirocin (single dose part): 00h00, 1h00, 02h00, 04h00, 06h00, 08h00, 12h00; Other Names: intranasal concentrations; Other: Collection of urine after Single dose part; Collection of urine during 12 hours after the application of mupirocin (Single dose part)
Experimental: Single dose part : 500mg mupirocin; Single dose part = single dose of 500 mg mupirocin in each nostril	Biological: blood samples after Single dose part; 3 blood samples will be performed sampling time ater application of mupirocin (single dose part): 00h30, 1h00, 02h00; Diagnostic test: nasal swab after Single dose part; 7 nasal swab for the detection of S. aureus (type Swab) will be performed after application of mupirocin (single dose part): 00h00, 1h00, 02h00, 04h00, 06h00, 08h00, 12h00; Other Names: intranasal concentrations; Other: Collection of urine after Single dose part; Collection of urine during 12 hours after the application of mupirocin (Single dose part); Drug: Mupirocin (500 mg); 500 mg de mupirocin; Other Names: Bactroban
Experimental: Repeated dose part: Group 1 - 50 mg of mupirocin twice a day; 50 mg of mupirocin in each nostril twice a day (morning and evening) for 5 days	Drug: Mupirocin (50 mg); 50 mg de mupirocin; Other Names: Bactroban; Diagnostic test: nasal swab during Repeated dose part; 5 nasal swab for the detection of S. aureus (type Swab) will be performed during administration of mupirocin (Repeated dose part): 2, 3, 4, 5 et 6 days after the first application of mupirocin (Repeated dose part); Other: Collection of urine during Repeated dose part; 5 collections of urine during Repeated dose part: 2, 3, 4, 5 et 6 days after the first application of mupirocin (Repeated dose part); Other: nasal swab after Repeated dose part; 2 nasal swab for the detection of S. aureus (type Swab) will be performed: 1, 3 months after the first application of mupirocin (Repeated dose part)
Experimental: Repeated dose part: Group 2 50 mg of mupirocin 3 times a day; 50 mg of mupirocin in each nostril 3 times a day (morning, noon and evening) for 5 days	Drug: Mupirocin (50 mg); 50 mg de mupirocin; Other Names: Bactroban; Diagnostic test: nasal swab during Repeated dose part; 5 nasal swab for the detection of S. aureus (type Swab) will be performed during administration of mupirocin (Repeated dose part): 2, 3, 4, 5 et 6 days after the first application of mupirocin (Repeated dose part); Other: Collection of urine during Repeated dose part; 5 collections of urine during Repeated dose part: 2, 3, 4, 5 et 6 days after the first application of mupirocin (Repeated dose part); Other: nasal swab after Repeated dose part; 2 nasal swab for the detection of S. aureus (type Swab) will be performed: 1, 3 months after the first application of mupirocin (Repeated dose part)
Experimental: Repeated dose part: Group 3 500 mg of mupirocin twice a day; 500 mg of mupirocin in each nostril twice a day (morning and evening) for 5 days	Drug: Mupirocin (500 mg); 500 mg de mupirocin; Other Names: Bactroban; Diagnostic test: nasal swab during Repeated dose part; 5 nasal swab for the detection of S. aureus (type Swab) will be performed during administration of mupirocin (Repeated dose part): 2, 3, 4, 5 et 6 days after the first application of mupirocin (Repeated dose part); Other: Collection of urine during Repeated dose part; 5 collections of urine during Repeated dose part: 2, 3, 4, 5 et 6 days after the first application of mupirocin (Repeated dose part); Other: nasal swab after Repeated dose part; 2 nasal swab for the detection of S. aureus (type Swab) will be performed: 1, 3 months after the first application of mupirocin (Repeated dose part)
Experimental: Repeated dose part: Group 4 500 mg of mupirocin 3 times a day; 500 mg of mupirocin in each nostril 3 times a day (morning non and evening) for 5 days	Drug: Mupirocin (500 mg); 500 mg de mupirocin; Other Names: Bactroban; Diagnostic test: nasal swab during Repeated dose part; 5 nasal swab for the detection of S. aureus (type Swab) will be performed during administration of mupirocin (Repeated dose part): 2, 3, 4, 5 et 6 days after the first application of mupirocin (Repeated dose part); Other: Collection of urine during Repeated dose part; 5 collections of urine during Repeated dose part: 2, 3, 4, 5 et 6 days after the first application of mupirocin (Repeated dose part); Other: nasal swab after Repeated dose part; 2 nasal swab for the detection of S. aureus (type Swab) will be performed: 1, 3 months after the first application of mupirocin (Repeated dose part)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
plasma concentrations of mupirocin	mupirocin pharmacokinetics	0 hours 30 after mupirocin application (Single dose part)
plasma concentrations of mupirocin	mupirocin pharmacokinetics	1 hours after mupirocin application (Single dose part)
plasma concentrations of mupirocin	mupirocin pharmacokinetics	2 hours after mupirocin application (Single dose part)
intranasal concentrations of mupirocin	mupirocin pharmacokinetics	1 hours after mupirocin application (Single dose part)
intranasal concentrations of mupirocin	mupirocin pharmacokinetics	2 hours after mupirocin application (Single dose part)
intranasal concentrations of mupirocin	mupirocin pharmacokinetics	4 hours after mupirocin application (Single dose part)
intranasal concentrations of mupirocin	mupirocin pharmacokinetics	6 hours after mupirocin application (Single dose part)
intranasal concentrations of mupirocin	mupirocin pharmacokinetics	8 hours after mupirocin application (Single dose part)
intranasal concentrations of mupirocin	mupirocin pharmacokinetics	12 hours after mupirocin application (Single dose part)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
presence of Staphylococcus aureus	Measured by nasal swab results	Days: 5 after mupirocin application (Repeated dose part)
presence of Staphylococcus aureus	Measured by nasal swab results	Days: 6 after mupirocin application (Repeated dose part)
presence of Staphylococcus aureus	Measured by nasal swab results	Days: 30 after mupirocin application (Repeated dose part)
presence of Staphylococcus aureus	Measured by nasal swab results	Days: 90 after mupirocin application (Repeated dose part)
urinary concentrations of monic acid	Analysis collection urine.	Days: 2 after mupirocin application (Repeated dose part)
urinary concentrations of monic acid	Analysis collection urine.	Days: 3 after mupirocin application (Repeated dose part)
urinary concentrations of monic acid	Analysis collection urine.	Days: 4 after mupirocin application (Repeated dose part)
urinary concentrations of monic acid	Analysis collection urine.	Days: 5 after mupirocin application (Repeated dose part)

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Saint Etienne
• Investigators: Principal Investigator: Kasra AZARNOUSH, MD PhD, CHU Saint-Etienne

Study record dates

Study Major Dates

• Study Start (Actual): February 29, 2024
• Primary Completion (Estimated): November 1, 2024
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: April 8, 2024
• First Submitted That Met QC Criteria: April 11, 2024
• First Posted (Actual): April 16, 2024

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 11, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Staphylococcus Aureus; Pharmacokinetic; Mupirocin
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Staphylococcal Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Mupirocin
• Other Study ID Numbers: 20CH024; 2020-006105-30 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No