Treatment of Methicillin-sensitive Staphylococcus Aureus (MSSA) (CLINDOS)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01500837
First received: November 28, 2011
Last updated: September 17, 2013
Last verified: September 2010
  Purpose

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.


Condition Intervention
Osteoarticular Infection
Drug: association of RIFAMPIN + CLINDAMYCIN
Drug: association of LEVOFLOXACIN+ CLINDAMYCIN

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Measurement of peak and trough serum concentrations of clindamycin [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    Measurement of peak and trough serum concentrations of clindamycin will be performed at Day 1, Day 15 and Day 30


Secondary Outcome Measures:
  • proportion of patients healing (as determined from absence of fever, absence of pain and favorable aspect of scar). [ Time Frame: Day 30 ] [ Designated as safety issue: No ]

Enrollment: 23
Study Start Date: October 2010
Study Completion Date: October 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: RIFAMPIN
CLINDAMYCIN + RIFAMPIN
Drug: association of RIFAMPIN + CLINDAMYCIN
association of RIFAMPIN + CLINDAMYCIN
Other Name: RIFAMPIN
Active Comparator: LEVOFLOXACIN
CLINDAMYCIN + LEVOFLOXACIN
Drug: association of LEVOFLOXACIN+ CLINDAMYCIN
association of LEVOFLOXACIN+ CLINDAMYCIN
Other Name: LEVOFLOXACIN

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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, ...).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01500837

Locations
France
Assistance Publique Hopitaux de Paris
Paris, France, 75015
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Study Director: Brigitte Sabatier, PD, PhD Department of Pharmacology
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01500837     History of Changes
Other Study ID Numbers: K000000
Study First Received: November 28, 2011
Last Updated: September 17, 2013
Health Authority: France: Committee for the Protection of Personnes

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Staphylococcus aureus
osteoarticular infection
clindamycin
serum concentration
orthopedic surgery

Additional relevant MeSH terms:
Infection
Communicable Diseases
Levofloxacin
Ofloxacin
Rifampin
Clindamycin
Clindamycin palmitate
Clindamycin phosphate
Anti-Infective Agents, Urinary
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Renal Agents
Anti-Bacterial Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antibiotics, Antitubercular
Antitubercular Agents
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors
Protein Synthesis Inhibitors

ClinicalTrials.gov processed this record on September 16, 2014