Treatment of Methicillin-sensitive Staphylococcus Aureus (MSSA)

NCT01500837 | Completed

• 1 other identifier: K000000
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

Background: One of the leading causes of peri-operative osteoarticular infections (OAI) is Staphylococcus aureus. Treatment usually requires surgical debridement in association with appropriate antibiotic therapy. After surgery, an intravenous (IV) antibiotic therapy is routinely indicated for 10 to 15 days, followed by a minimal one-month oral treatment. In this protocol, the latter includes clindamycin in combination with rifampin or levofloxacin. Clindamycin is considered a good option in staphylococcal infections, because of its action against biofilm formation and bacterial adherence, its high level of joint and bone penetration and its good tolerance. Rifampin, a potent cytochrome P-450 inducer, enhances the elimination of a large number of drugs. Therefore, an influence of rifampin on clindamycin pharmacokinetics must be considered. Objectives: The primary objective is to compare the influence of rifampin and levofloxacin respectively on the pharmacokinetics of clindamycin in a randomized series of peri-operative staphylococcal OAI. The investigators then seek to determine the optimal drug association with regard to infection control and drug tolerance. Study design: Monocentric, randomized, open label, comparative study Study period: From November 2010 to October 2011. Materials and Methods: Following surgical debridement and after 10 to 15 days of IV antibiotherapy, patients are randomly assigned either to the "clindamycin/rifampin" arm either to the "clindamycin/levofloxacin" arm, according to the antimicrobial susceptibility testing. Peak and trough serum concentrations of clindamycin are measured at day-1, day-15 and day-30 of oral treatment. Rifampin and levofloxacin serum concentrations are measured at the same intervals to monitor patient compliance.

Conditions

Osteoarticular Infection

Keywords

Staphylococcus aureus; osteoarticular infection; clindamycin; serum concentration; orthopedic surgery

Outcome Measures

Primary Outcomes (1)

• Measurement of peak and trough serum concentrations of clindamycin

  Measurement of peak and trough serum concentrations of clindamycin will be performed at Day 1, Day 15 and Day 30

  1 month

Secondary Outcomes (1)

• proportion of patients healing (as determined from absence of fever, absence of pain and favorable aspect of scar).

  Day 30

Study Arms (2)

RIFAMPIN

ACTIVE COMPARATOR

CLINDAMYCIN + RIFAMPIN

Drug: association of RIFAMPIN + CLINDAMYCIN

LEVOFLOXACIN

ACTIVE COMPARATOR

CLINDAMYCIN + LEVOFLOXACIN

Drug: association of LEVOFLOXACIN+ CLINDAMYCIN

Interventions

association of RIFAMPIN + CLINDAMYCIN DRUG

association of RIFAMPIN + CLINDAMYCIN

Also known as: RIFAMPIN

RIFAMPIN

association of LEVOFLOXACIN+ CLINDAMYCIN DRUG

association of LEVOFLOXACIN+ CLINDAMYCIN

Also known as: LEVOFLOXACIN

LEVOFLOXACIN

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• subject over 18 years with a IOA with GERME sensitivity to three antibiotics,
• Patient in orthopedic unit of HEGP,
• Patient who received and understood the information and who signed consent,

You may not qualify if:

• Known allergy to one of three antibiotics and / or excipients,
• Pregnancy or during lactation,
• Congenital galactosemia, malabsorption of glucose and galactose, or lactase deficiency,
• History of tendinopathy with fluoroquinolones,
• G6PD deficiency,
• porphyria,
• subject receiving a protease inhibitor,
• subject receiving anticoagulants
• Malabsorption syndrome,
• subject unable to follow the protocol (organizational problem, intellectual disability, ...).

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Assistance Publique Hopitaux de Paris

Paris, 75015, France

Location

Related Publications (1)

• Bernard A, Kermarrec G, Parize P, Caruba T, Bouvet A, Mainardi JL, Sabatier B, Nich C. Dramatic reduction of clindamycin serum concentration in staphylococcal osteoarticular infection patients treated with the oral clindamycin-rifampicin combination. J Infect. 2015 Aug;71(2):200-6. doi: 10.1016/j.jinf.2015.03.013. Epub 2015 Apr 30.

  PMID: 25936632 DERIVED

MeSH Terms

Conditions

Staphylococcal Infections

Interventions

Clindamycin; Rifampin; Levofloxacin

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Lincomycin; Lincosamides; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Glycosides; Carbohydrates; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Ofloxacin; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring

Study Officials

• Brigitte Sabatier, PD, PhD

  Department of Pharmacology

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 28, 2011
• First Posted: December 29, 2011
• Study Start: October 1, 2010
• Primary Completion: October 1, 2011
• Study Completion: October 1, 2011
• Last Updated: September 18, 2013

Record last verified: 2010-09

Locations

FR (1)