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

• ClinicalTrials.gov Identifier: NCT02782078
• Recruitment Status: Completed
• First Posted: May 25, 2016
• Last Update Posted: March 27, 2020
• Sponsor: Assistance Publique - Hôpitaux de Paris
• Information provided by (Responsible Party): Assistance Publique - Hôpitaux de Paris

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Staphylococcal Infections	Biological: Clindamycin and rifampicin dosages	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pharmacological Interaction of Rifampicin on Clindamycin in Staphylococcic Osteoarticular Infections
• Actual Study Start Date: March 6, 2017
• Actual Primary Completion Date: December 12, 2018
• Actual Study Completion Date: January 3, 2019

Arms and Interventions

Arm	Intervention/treatment
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)

Outcome Measures

Primary Outcome Measures :

1. clindamycin AUC (area under curve) at steady state and after rifampicin introduction [ Time Frame: clindamycin AUC will be evaluated after rifampicin interaction, so at day 14 of introduction ]
   this AUC of clindamycin will be compared to AUC before rifampicin introduction, at day 0

Secondary Outcome Measures :

1. rifampicin auto induction [ Time Frame: AUC of rifampicin at day 4 (before autoinduction ant at steady state) and day 14 (after autoinduction) ]
   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
2. clinical outcome [ Time Frame: at day 4, day 14, day 28 (or day 60 if osteosynthesis) ]
   resolution of symptoms first described (pain, swelling, fever…) with specific scale
3. biological outcome [ Time Frame: at day 4, day 14, day 28 (or day 60 if osteosynthesis) ]
   resolution of inflammatory syndrome (measure of C reactive protein) and hyperleucocytosis (WBC)
4. side effects and toxicity: number of participants with treatment related adverse events as assessed by CTCAE v4.0 [ Time Frame: at day 2, day 4, day 14, day 28 (or day 60 if osteosynthesis) ]
   skin lesion, digestive symptoms, clostridium infection, liver cytolysis, hematological disorders (leucopenia, hemolytic anemia, thrombopenia)…

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

France

Service de Médecine Interne - Hôpital Bichat Claude Bernard

Paris, France, 75018

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Investigators

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

More Information

• Responsible Party: Assistance Publique - Hôpitaux de Paris
• ClinicalTrials.gov Identifier: NCT02782078
• Other Study ID Numbers: P140318 / AOR14027
• First Posted: May 25, 2016
• Last Update Posted: March 27, 2020
• Last Verified: March 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Assistance Publique - Hôpitaux de Paris:

osteoarticular infection; rifampicin; clindamycin; enzymatic induction; antibiotherapy resistance

Additional relevant MeSH terms:

Clindamycin; Clindamycin palmitate; Clindamycin phosphate; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Infections; Communicable Diseases; Staphylococcal Infections; Disease Attributes; Pathologic Processes; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Rifampin; Anti-Bacterial Agents; Anti-Infective Agents; Protein Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antibiotics, Antitubercular; Antitubercular Agents; Leprostatic Agents; Nucleic Acid Synthesis Inhibitors; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers