Treatment of Methicillin-sensitive Staphylococcus Aureus (MSSA)

Osteoarticular Infection Clinical Trial

— CLINDOS  

Official title:

Treatment of Methicillin-sensitive Staphylococcus Aureus Orthopaedic Infections With Clindamycin in Combination With Rifampin or Levofloxacin: a Randomized Pharmacological and Clinical Study (the CLINDOS Trial)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01500837
• Other study ID #: K000000
• Status: Completed
• Phase: N/A
• First received: November 28, 2011
• Last updated: September 17, 2013
• Start date: October 2010
• Est. completion date: October 2011

Study information

• Verified date: September 2010
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Committee for the Protection of Personnes
• Study type: Interventional

Clinical Trial 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.

Description:

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. Infection cure is evaluated clinically, with periodic X-rays and CRP dosage in serum.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: October 2011
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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,

Exclusion Criteria:

• 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, ...).

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Infection
• Osteoarticular Infection

Intervention

Drug:
• association of RIFAMPIN + CLINDAMYCIN
association of RIFAMPIN + CLINDAMYCIN
• association of LEVOFLOXACIN+ CLINDAMYCIN
association of LEVOFLOXACIN+ CLINDAMYCIN

Locations

Country	Name	City	State
France	Assistance Publique Hopitaux de Paris	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	proportion of patients healing (as determined from absence of fever, absence of pain and favorable aspect of scar).		Day 30	No