Pharmacological Interaction of Rifampicin on Clindamycin in Staphylococcic Osteoarticular Infections (DALARI)

Clindamycin and rifampicin are authorized in osteoarticular infection treatment (IDSA guidelines) but some interaction is observed. The objective of this study is to evaluate and quantify rifampicin interaction on clindamycin

Study Overview

• Status: Completed
• Conditions: Staphylococcal Infections
• Intervention / Treatment: Biological: Clindamycin and rifampicin dosages

Detailed Description

It could suggest modification of recommended doses or incitement to antibiotic dosage. Thus, theses antibiotics, if association is allowed, could limit fluoroquinolones prescription and avoid some antibiotic resistance.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Paris, France, 75018
    • Service de Médecine Interne - Hôpital Bichat Claude Bernard

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• patients ≥18 years of age
• osteoarticular infection
• staphylococcus detected in bacteriological sampling
• sensibility to rifampicin, erythromycin and clindamycin
• active intravenous antibiotherapy against staphylococcus detected in bacteriological sampling

Exclusion Criteria:

• septic shock or severe initial sepsis
• osteoarticular infection with other microorganism than staphylococcus
• contraindication to clindamycin or rifampicin including case of hypersensibility to one of these two antibiotics
• pre-existing renal insufficiency or severe renal insufficiency (creatinine clearance <30 ml/min)
• serious cognitive disorders
• patient under guardianship, trusteeship or non affiliated to social security or CMU (beneficiary or assignee)
• refusal to take part in the study and to sign the consent form
• pregnancy
• lactation
• administration of clindamycin or rifampicin within the month before inclusion
• treatment with enzymatic inductor or inhibitor within the month before inclusion
• participation to another study modifying antibiotic treatment administration

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Clindamycin and rifampicin dosages; blood samples for clindamycin and rifampicin dosages (for each patient)	Biological: Clindamycin and rifampicin dosages; blood samples for clindamycin and rifampicin dosages (for each patient)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
clindamycin AUC (area under curve) at steady state and after rifampicin introduction	this AUC of clindamycin will be compared to AUC before rifampicin introduction, at day 0	clindamycin AUC will be evaluated after rifampicin interaction, so at day 14 of introduction

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
rifampicin auto induction	rifampicin autoinduction will be studied with rifampicin AUC, according time, for each patient, at day 4 and day 14. Comparison of AUC with student's test	AUC of rifampicin at day 4 (before autoinduction ant at steady state) and day 14 (after autoinduction)
clinical outcome	resolution of symptoms first described (pain, swelling, fever…) with specific scale	at day 4, day 14, day 28 (or day 60 if osteosynthesis)
biological outcome	resolution of inflammatory syndrome (measure of C reactive protein) and hyperleucocytosis (WBC)	at day 4, day 14, day 28 (or day 60 if osteosynthesis)
side effects and toxicity: number of participants with treatment related adverse events as assessed by CTCAE v4.0	skin lesion, digestive symptoms, clostridium infection, liver cytolysis, hematological disorders (leucopenia, hemolytic anemia, thrombopenia)…	at day 2, day 4, day 14, day 28 (or day 60 if osteosynthesis)

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Tiphaine Goulenok, MD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): March 6, 2017
• Primary Completion (Actual): December 12, 2018
• Study Completion (Actual): January 3, 2019

Study Registration Dates

• First Submitted: May 2, 2016
• First Submitted That Met QC Criteria: May 20, 2016
• First Posted (Estimate): May 25, 2016

Study Record Updates

• Last Update Posted (Actual): March 27, 2020
• Last Update Submitted That Met QC Criteria: March 26, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: clindamycin; rifampicin; osteoarticular infection; enzymatic induction; antibiotherapy resistance
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Infections; Communicable Diseases; Staphylococcal Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-Bacterial Agents; Leprostatic Agents; Protein Synthesis Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Antitubercular Agents; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Rifampin; Clindamycin; Clindamycin palmitate; Clindamycin phosphate
• Other Study ID Numbers: P140318 / AOR14027

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